Aging Matters Magazine V3 Issue 38 2021, STRESS IS GOOD! by International Antiaging Systems (IAS)

V3 ISSUE 38 2021 US $10 / EU €8 / GB £7

The IAS private members club magazine

STRESS IS GOOD!

In this issue: Professor Suresh Rattan explains hormesis Supplements for cancer by Marios Kyriazis, MD NAD for longer lifespans Natural antivirals

Testimonials Suzanne Somers “The Aging Matters™ magazine is spectacular, very readable and chock full of the latest and greatest. It’s the magazine I wait for and anticipate.”

Aubrey de Grey PH.D “IAS has shown great vision and leadership as an organization focused mainly on the provision of contemporary medical interventions against aging, and in also supporting the SENS Foundation efforts to hasten the development of much more powerful future interventions.”

Nicholas Perricone M.D. “IAS is an outstanding resource for the finest, most up-to-date news and information on healthy aging. They also offer products of the highest integrity and efficacy. In fact, IAS is the world’s greatest source, (often the only source) for the most cutting-edge and advanced nutrients to ensure optimum health span and maximum life span.”

Thierry Hertoghe, M.D.

Jonathan V. Wright M.D. “Every adult has the right to take care of his or her own personal health as he or she chooses. In the 21st century this universal human right has been nearly obliterated by an ocean of nanny state regulations and deliberate suppression of information by bureaucracies, with hidden and not-so hidden agendas. International Antiaging Systems is a beacon of useful health care information and a literal island of freedom of health care product choice in our otherwise unfree health care world.”

“IAS have a history of making throughout the world crucial, but difficult to access medications available to patients. IAS is one of the pioneering societies in antiaging medicine that has helped this new medical speciality move forward.”

Walter Pierpaoli, M.D. “I have known IAS for many years’ and they are a qualified group who provide for me, my family and my patients. Their skill and professional capacity have liberated me from all sorts of problems concerning the search for guaranteed and often rare supplements, or anything which is available but problematic to find. Their service goes far beyond duty and helps in many ways to maintain optimal health.”

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Frank Shallenberger M.D. “The tools that are available today to treat the aging process are truly amazing. Thanks to IAS the field of antiaging medicine has expanded to the point that feeling and functioning 10-20 years younger is easily achievable. Their information and product services are regularly used by my patients.”

Contents

Welcome

Testimonials Professionals’ comment on IAS

The science of aging interventions Professor Rattan explains hormesis

02 03 04 14

Nutrition in cancer prevention & therapy Dr. Marios Kyriazis documents what is useful

NAD for longer lifespans Discover the work of Dr. David Sinclair

Welcome To the second edition of 2021 Forefront Recent stories in the news

Natural antivirals How mushroom extracts and BHT help Spotlights A few details about special products

32 38

Media Page Introducing our recommended videos

Antiaging-Systems.com Where to find what you need

Declaration: The IAS Aging Matters™ magazine is intended for IAS private club members (and therefore is not intended for the public). It focuses on the latest international nutritional, hormonal and drug therapies to help combat the signs of aging. These signs include the physical, mental, and internal changes consisting of the diseases and disorders such as cancer, arthritis, and senile dementias etc. However, the focus is upon the prevention of such aging diseases and disorders for the ‘healthy-aging’ individual. Copyright 2021: All copyrights are acknowledged. Whilst every effort has been made to ensure accuracy, no responsibility can be accepted for illustrations, photographs, artwork, or advertising materials while in transmission or with the publisher or their agents. Disclaimer: All educational information is offered strictly under IAS terms and conditions. This information does not replace the advice of your physician and restrictions may apply in some countries. The opinions expressed by the writers may not be those of IAS, nor the magazine. Terms and conditions are subject to change without notice.

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As we head for the middle of 2021, we look to an issue that covers a wide range of topics, all related to health, well-being, and longevity. Firstly, we are honored to have Professor Suresh Rattan from Denmark, (a very prominent individual in the field of biogerontology), tell us about hormesis. This is essentially mild stress, and it can be beneficial for our health, perhaps the most obvious example is exercise. But Professor Rattan also talks about agents that are hormetins, in other words they are agents that can benefit via the pathway of hormesis. Dr. Marios Kyriazis follows this by describing nutrition that has shown benefit in the prevention and in various therapies for different cancer states. Dr. Kyriazis expands on those which also have hormetic effects, and hence we can see the relation between agents that benefit both cancer and longevity. Many people have become aware of the research of Dr. David Sinclair. Some of you may have read his best-selling book called ‘Lifespan.’’ It basically introduces and details the ability to enhance our internal NAD+ levels, and what that can mean to help us to equivocate our healthspan to our lifespan. We explore the NAD boosters and other ancillary agents that have been shown to naturally increase NAD. Our last article is focused on natural antivirals, particularly those found in mushroom extracts and BHT. Here, Mr. Will Block has researched them finding out about their efficacy in a wide range of pathogens, including viruses and bacteria etc., there is a particular worthy note for those concerned about herpes. Hopefully, you may notice some subtle design changes. We are adapting over time to keep the magazine fresh, as well as maintaining its upto-date information. One such new feature is the media page. It will highlight our Antiaging Systems You Tube channel. To view them you will see their weblinks and QR codes. Likewise, to save paper, the full references of an article can now be found in the same way. Forever onward and upward!

www.aging-matters.com Your comments are welcome at: editor@aging-matters.com

Phil Micans, MS, PharmB Editor, Aging Matters™ Magazine Ward Dean, M.D. Medical Director, IAS Group Aging Matters | 3 |

Forefront

CAN SUN-DAMAGED SKIN BE REVERSED? Here comes the sun! It’s that time of year when sun-worshippers cook like sausages, the fairskinned look even paler from layers of hard to rub in suntan lotion and the fake tanned reveal their orange hands, elbows and knees. In this article, we are asking the question, can sun-damaged skin be reversed? I have some good news for you. Skin sun damage starts when we are young… Sun damage to the skin starts at a young age but doesn’t reveal itself until many years later. Too much exposure to the sun’s UV (ultraviolet) rays can break down collagen and elastin fibres. The fibres that we need to keep our skin smooth and tight, the same fibres that we produce less of as we age. In conclusion, too much sun exposure and the depleting production of collagen and elastin as we age results in photoaging and crepey skin. Photoaging and crepey skin… Photoaging or photodamage is the term used to describe how repeated sun exposure prematurely ages the skin causing DNA changes to skin cells resulting in wrinkles. It can cause skin pigmentation changes, age spots, freckles, and a decrease | 4 | Aging Matters

in skin elasticity. As we age we produce less natural oils, oils that are needed to seal moisture into the skin preventing it from drying out. Photoaging causes crepey skin, much like the crepe paper we would use at school to make creative art collages. If you remember, the multi-coloured crepe paper felt weird and was almost impossible to smooth out. ‘Crepey skin’ is a recognised condition, the skin looks and feels dry and made a lot worse by sunburn from overexposure to UV rays.

awareness of sun-damaged skin has increased, the younger generation are well educated about it. It is important to protect your skin from UV rays because 65% of cancerous melanomas are caused by sun rays. Please visit your doctor if you have concerns about moles on your body. Can sun-damaged skin be reversed? I read what the experts say. It’s good news!

You can see the instant damage to cells and blood vessels in the skin when you get sunburnt, and this can result in the leathery skin texture that you see on people who spend a large majority of their time outside.

According to dermatology specialists Dr Susan Bard and Dr Hadley King, it is possible to partially reverse some types of sun damage on your skin. If you have wrinkles, fine lines or other characteristics of sun damage a dermatologist can help you smooth out your skin.

The severity of sunburn (firstdegree burns) depends on the type of skin type and time in the sun. Thankfully,

Specialists use lasers, chemical peels and certain topical medications to treat or destroy sun-damaged skin.

Factional Laser Treatment (Fraxel) During factional laser treatment, the lasers heat small areas under the skin which encourages regrowth of collagen that supports the skin and smooths out wrinkles from the inside out. Ultrasound treatment (Ulthera) Ulthear is a skin tightening procedure using targeted ultrasound. Heat breaks down some of the cells and stimulates the growth of collagen to tighten skin. The treatment uses concentrated ultrasound waves to create heat deep within the dermis and SMAS muscle. Chemical peels Chemical peels improve the appearance of sun-damaged skin by using a solution to remove the outer layer of old skin.

The new skin that replaces it is usually smoother and less wrinkled in appearance. Topical medications Prescription creams such as tretinoin are frequently used for sun-damaged skin. Most dermatologists recommend applying tretinoin cream or gel daily. Talk to your doctor or chemist to find a cream that is appropriate for your skin type. Curaderm (BEC5) cream – BEC5 cream, also known as Curaderm, is an effective, convenient and non-invasive treatment for non-melanoma skin cancer. Curaderm cream is particularly potent when used to treat basal-cell carcinomas (BCC) and squamous cell carcinomas (SCC), although it is also effective on benign tumours such as sunspots, age spots, Keratoses and Keratocanthmoas.

Don’t stay out of the sun… Overexposure to the sun’s rays is bad for you but there are great benefits to be had from being in the sun too, physically, and mentally. The sun is mood-lifting, it triggers the release of serotonin in the brain which helps keep you calm and relaxed. Without that release people can become depressed and develop the condition SAD (seasonal affective disorder). Experts recommend that people should expose themselves to sunlight for 5 – 15 minutes a day for it to be beneficial. Even though too much sun puts you at high risk of skin cancer, a balanced approach can help reduce the risks of certain cancers. Other benefits are: ► The sun encourages the body to produce Vitamin D which is good for the skin and bone health. ► The sun can help to heal psoriasis, eczema, jaundice and acne. ► The sun can also help relieve the symptoms of arthritis, lupus and bowel disease.

Aging Matters | 5 |

Forefront Looking after yourself is important and here are the best things you can do to help prevent sun-damaged skin: ► Always wear sunscreen when you are outside, one with an SPF (sun protection factor) of at least 30.

► Keep your skin moisturised.

► Wear sunglasses to protect the eyes.

► Use exfoliants to remove dead skin.

► Avoid using sunbeds.

► Drink plenty of water to hydrate our skin.

► Apply extra cream on large moles or scars.

Like a lot of things in life it’s about getting a balance when it comes to exposure to the sun.

► If you get sunburn, take a cold shower to cool the skin down and apply an aftersun product.

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Disclaimer: All educational information is provided under the IAS terms and conditions (which may change without notice) and does not replace the advice of your physician. Restrictions may apply in some countries.

www.antiaging-systems.com

► Have a good skincare routine every day.

► Eat a diet high in antioxidants.

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“I get my MZS and TRH from IAS” Suzanne Somers

DISCLAIMER: All educational information is provided under IAS terms and conditions which may change without notice. Restrictions may apply in some countries. Aging Matters | 7 |

Forefront

CV19, IVERMECTIN AND D3 Given all the COVID-19 suffering, the promise for relief, and the growing vaccine sideeffects, is it any wonder that a fervent search for other drugs and supplements is growing? Dr. Ryan Cole, the CEO/ Medical Director of Cole Diagnostics, an independent IDAHO lab, may have some answers. Dr. Cole has seen over 350,000 patients in his career and conducted over 100,000 COVID-19 tests. Dr. Cole has this to say about vitamin D3 (hereafter named as vitamin D): ► Coronavirus infections are seasonal. ► In reality, there are only low vitamin D seasons. ► Inflammatory (cytokine storms), are present in all COVID-19 cases and cannot be controlled without adequate vitamin D levels. ► Massive numbers of Americans have low vitamin D levels. ► 96% of ICU patients are vitamin D deficient. In reality, there are only low vitamin D seasons. ► You cannot synthesize vitamin D from sunlight during fall and winter at 35-degrees north and above.

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► If you live in northern climates, you are immune suppressed if you do not supplement with vitamin D during fall and winter. ► Scandinavian countries (Finland, Norway, Sweden, Denmark) test their citizens twice a year for vitamin D and fortify 35 foods with vitamin D. ► But many populations are left vulnerable to any seasonal viral infectionwithout a public health program to promote vitamin D adequacy.

► There is no social disparity of care, but darker skin pigmentation inhibits sunshine vitamin D synthesis in the skin. ► Fauci says he personally takes 8,000-9,000 units of vitamin D per day. Why has this has not become a public health message? ► The top three public health messages should be: 1. Vitamin D 2. Vitamin D 3. Vitamin D

Ivermectin Arrives Ivermectin fits the treatment bill. Four billion doses of Ivermectin have safely been taken. Of the half million COVID-19 deaths in North America, there would be 375,000 less deaths if Ivermectin were administered! Public health officials may have blood on their hands. 100% of Ivermectin treated patients don’t get ill. This works for all genetic variants. Pre-Covid Cocktail For patients desiring protection before possible exposure to COVID-19, such as travel into high-risk areas, a combination of Ivermectin, zinc, vitamin C, and vitamin D is recommended as part of the safety plan. Dosages are as follows: Ivermectin treatment under supervision, is typically being dosed at 0.2 mg per kg bodyweight, each 24hour period. Another way to calculate your personal treatment dose; divide your body weight in pounds by 33. That’s how many Ivermectin 3 mg tablets you should take in one day. Take that many tabs on days 1, 3, 10, 17, and 25 (one month supply). In addition: ►► Zinc Sulfate 50 mg/daily ►► Vitamin C 3-5,000 mg/daily ►► Vitamin D3 4-5,000 IU/daily

Ivermectin Enters the Field Recently, several groups of physicians and multidisciplinary committees have recommended that the Honduran government establish a new public health policy to administer weekly doses of Ivermectin (12 to 18 mg) in the healthy adult population. [Editor’s note: Those with ‘lessor’ concerns, are typically availing themselves of a prophylactic dose of ivermectin as little as 3 mg per week]. This is because there are clinical and laboratory study results that justify its use for prophylaxis and to lower the viral load of SARSCoV-2, which is the virus that causes COVID-19. The Problem of “Experts” And the public and the news media always take great comfort that an “expert” gave them this idea based on the “science.” Trouble is, you can always find another “expert” with equal credentials who will offer a completely contradictory perspective. Also, the Honduran government may not parallel other Latin-American countries, let alone European or SE Asian nations. Ivermectin as a Wonder Drug Ivermectin proposes SO many potential effects to treat a range of diseases, with its

antimicrobial, antiviral, and anti-cancer properties that it has been referred to as a wonder drug. [1] It is highly effective against many microorganisms including some viruses. In a recent comprehensive systematic review, the antiviral effects of Ivermectin appear to work on RNA viruses such as Zika, dengue, yellow fever, West Nile disease, etc. Inflammation is an intrinsic defense mechanism triggered by the immune system against infection or injury. Chronic inflammation allows the host to recover or adapt through cellular and humoral responses, whereas acute inflammation leads to cytokine storms, which can result in tissue damage. In a recent review, the paper presented the overlapping outcomes of cancer inflammation with virusinduced inflammation. [2] The study emphasizes how antiinflammatory drugs that work against cancer inflammation may ALSO work against the inflammation caused by the COVID-19 viral infection. FDA Prevails … In Error The FDA does not approve Ivermectin for COVID-19, owing to a variety of possible side-effects. Ha! But this does not include vaccines, which ironically are proving to have many potentially harmful side effects, including blood clots for AstraZenica’s vaccine. Aging Matters | 9 |

Forefront Patients were randomized to receive Ivermectin, 300 μg/ kg of body weight per day for 5 days (n=200) or placebo (n=200). The Primary outcome was the time to resolution of symptoms within a 21-day follow-up period. Adverse events were also collected.

While cancer remains second among the diseases associated with mortality worldwide, cancer patients’ mortality rates are often observed over extended periods after illness, usually ranging from months to years. However, the mortality rates associated with COVID-19 disease are robust. Overlapping Inflammatory Mechanisms Since both cancer and COVID-19 disease share overlapping inflammatory mechanisms, repurposing some anticancer and anti-inflammatory drugs for COVID-19 may lower mortality rates. Here, are reviewed some of these inflammatory mechanisms. Also, the researchers propose some potential chemotherapeutic agents to mediate in them.[3] Also studied are the repercussions of anti| 10 | Aging Matters

inflammatory drugs such as glucocorticoids and hydroxychloroquine with zinc or antiviral drugs such as Ivermectin, against SARS-CoV-2 induced cytokine storm. Ivermectin Treats COVID-19 A new double-blind study has determined that Ivermectin is an efficacious treatment for mild COVID-19. [4] Conducted in Cali, Colombia, the study participants were identified by simple random sampling from the state’s health department electronic database of patients with symptomatic, laboratoryconfirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled during mid-2020 and followed up through December 21, 2020.

The median time to resolving of symptoms was 10-days in the Ivermectin group compared with 12 days in the placebo group. By day 21, 82% in the Ivermectin group and 79% in the placebo group had resolved symptoms. Comparative Effectiveness There is an urgent need for effective treatments to prevent or attenuate lung and systemic inflammation, endotheliitis, and thrombosis related to COVID-19. [5] The aim of yet one more study was to assess the effectiveness of a multidrug-therapy consisting of Ivermectin, Azithromycin, Montelukast and Acetylsalicylic Acid (“TNR4” therapy) to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico.[6] A comparative effectiveness study was performed among 768 confirmed SARS-CoV-2 cases aged 18 to 80 years, who received ambulatory care at the Ministry of Health of Tlaxcala, Mexico. A total of 481 cases received the TNR4 therapy, while 287 received another treatment (comparison group).

All participants received home visits and/or phone calls for clinical evaluation during the 14 days after enrollment. Nearly 85% of cases who received the TNR4 recovered within 14 days compared to 59% in the comparison group. Likelihood of recovery within 14 days was 3.4 times greater among the TNR4 group than in the comparison group. Patients treated with TNR4 had a 75% and 81% lower risk of being hospitalized or death, respectively than the comparison group. TNR4 therapy improved recovery and prevented risk of hospitalization and death among ambulatory COVID-19 cases. High Compound Library Screen In FDA-approved studies for parasitic indications, Ivermectin has been the focus of growing attention in the last 8 years due to its

potential as an antiviral. [6-7] Researchers first identified Ivermectin in a high throughput compound library screen as an agent potently able to inhibit recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host importin (IMP) α/β1 heterodimer. Ivermectin demonstrated its ability to bind directly to IMPα to cause conformational changes that prevent its function in nuclear import of key viral as well as host proteins. Cell culture experiments have shown strong antiviral action towards a range of viruses, including HIV1, dengue, Zika and West Nile Virus, Venezuelan equine encephalitis virus, Chikungunya, pseudorabies virus, adenovirus, and SARS-CoV-2 (which causes COVID-19). Close to 70 clinical trials are currently in progress worldwide for SARSCoV-2. Although few of

these studies have been completed, the results that are available, as well as those from observational/ retrospective studies, indicate clinical benefit. There is urgent therapeutic need for COVID-19, a disease for which there are currently no widely effective approved treatments and the emergency-use authorized drugs do not result in significant and widespread patient improvement. The FDA-approved drug Ivermectin has long been shown to be both an antihelmintic agent, (a group of antiparasitic drugs that expel parasitic worms [helminths]) and a potent inhibitor of viruses such as Yellow Fever Virus. More Potent Therapeutic Antiviral Dose In a current study, Ivermectin is packaged as an orally administrable nanoparticle that could serve as a vehicle to deliver a more potent therapeutic antiviral dose.

Aging Matters | 11 |

Forefront Stable isotope labeling by amino acids in cell culture (SILAC) quantitative proteomics was used to analyze human ovarian cancer cells treated with and without Ivermectin (20 μmol/L) for 24 h, which identified many Ivermectinrelated proteins in ovarian cancer cells. Gene Ontology analysis revealed 10 statistically significant cellular components, 13 molecular functions, and 11 biological processes.

It could also demonstrate efficacy to decrease expression of viral spike protein and its receptor angiotensin-converting enzyme 2 (ACE2), both of which are keys to lowering disease transmission rates. The study also reports that the targeted nanoparticle delivered Ivermectin can inhibit the nuclear transport activities mediated through heterodimers as a possible mechanism of action. Moreover, it sheds light on Ivermectin loaded, orally administrable, biodegradable nanoparticles. These can be a potential treatment option for the novel coronavirus through a multilevel inhibition. As both ACE2 targeting and the presence of spike protein are features shared among this class of virus, this platform technology | 12 | Aging Matters

has the potential to serve as a therapeutic tool not only for COVID-19 but for other coronavirus strains as well. Great Burden to Healthcare Worldwide Viruses such as human cytomegalovirus, human papillomavirus (HPV), EpsteinBarr virus, HIV, and SARSCoV-2, represent a great burden to human health worldwide. [8-9] The FDA-approved antiparasite drug Ivermectin is also an antibacterial, antiviral, and anticancer agent, which offers more potentiality to improve global public health, and it can effectively inhibit the replication of SARSCoV-2 in vitro. This study sought to identify Ivermectin-related virus infection pathway alterations in human ovarian cancer cells.

These findings demonstrate the broad-spectrum antiviral property of Ivermectin for COVID-19 treatment in the context of predictive, preventive, and personalized medicine in virusrelated diseases. Screening Identifies Potentially Effective Drugs The small molecule macrocyclic lactone Ivermectin, approved by the US Food and Drug Administration for parasitic infections, has received renewed attention in the last eight years due to its exciting potential as an antiviral. [10] Astonishingly, cell culture experiments show robust antiviral action towards HIV1, dengue virus, Zika virus, West Nile virus, Venezuelan equine encephalitis virus, Chikungunya virus, Pseudorabies virus, adenovirus, and SARS-CoV-2.

This mini-review discusses the case for Ivermectin as a host-directed broadspectrum antiviral agent for a range of viruses, including SARS-CoV-2. COVID-19 is a critical pandemic that has affected human communities worldwide and (we repeat) there is an urgent need to develop effective drugs. [11] Although there are many candidate drug-compounds that may be useful for treating COVID-19, the evaluation of these drugs is time-consuming and costly. Thus, screening to identify potentially effective drugs prior to experimental validation is necessary. Numerous drugs were successfully screened, including many known antiviral drug compounds such as sorafenib, sorafenib, alvocidib, mitoxantrone, geldanamycin, fluticasone, and quercetin. [12] One thing more … COVID-19 is likely mutating and is turning on younger age groups. [13] We will continue to report these scientific interventions, missteps, and discoveries with discernment.

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References: For more information scan this QR code

www.antiaging-systems.com Aging Matters | 13 |

THE SCIENCE OF AGING INTERVENTIONS

THE SCIENCE OF AGING INTERVENTIONS By Professor Suresh I. S. Rattan The science of aging research and its interventions is progressing at a rapid pace. The three pillars of health– food, physical activity, and social-mental engagement– are accessible to an hormetic way of life, using respective hormetins from various sources, including food supplements. Old age is a privilege, not a birthright This is because our species, just as all other species, has evolved to live up to an age that is essentially required for successful reproduction and continuation of generations. Such a natural or “essential lifespan” (ELS) for our species is about 45 years [1, 2]. It is a great achievement of human ingenuity with respect to social, medical, and technological developments that most of us can expect, and wish, to live much beyond our ELS. For most of the human history, living in old age was a rarity. Living beyond ELS allows aging phenotype to emerge- slowly, steadily, and progressively. Muscles become weaker and thinner. Bones become brittle and porous. Hormone levels decrease. Skin becomes wrinkled and dry. Hair stops growing and loses its color. Blood vessels become | 14 | Aging Matters

hardened and thickened. Energy levels become low. Seeing near and far becomes less sharp. Hearing becomes difficult. The ability to smell and taste is reduced. Digesting and absorbing food declines. Short term memory fails. That is not all and for some can be even worse. Crossing the threshold into chronic and progressive diseases of old age- dementia, sarcopenia, osteoporosis, cataracts, arthritis, and several cancers– becomes a reality. Old age is not good news I wish I had something positive to say about the body in old age. Any so-called positive traits of old age, for example experience, wisdom, empathy, and freedom, are socially constructed and, in modern times, are mostly wishful imaginaries. Obviously, such aging matters to all, and therefore demands action to do something about it.

About the author Professor Rattan is the head at the department of Molecular Biology and Genetics at Aarhus University in Denmark. He is a world renowned biogerontologist, researching the biology of aging, and in addition to his professional research work, he is also very much interested and involved in the public communication of its science.

So, what do we really want to do about aging and old age? ►► Do we want to reverse the biological changes that have occurred over time, and revert to some earlier age? ►► Or do we want to continue to age while becoming frail, but without ever crossing over the threshold of becoming clinically ill? ►► Or do we want to slow down the pace of aging, so that all age-related changes and deteriorations occur later, thus prolonging the lifespan and delaying death? ►► Or do we want to eliminate death and continue to live indefinitely?

THE SCIENCE OF AGING INTERVENTIONS

These questions are very important to think about, and these can help us to take a position as to how aging matters to us individually and collectively. What follows is my attempt to share my views based on my understanding of the biological basis of aging, that I have been able to sculpt by my active participation in doing biogerontological research and teaching over a period of 40 years. Such a scientific understanding of aging is necessary if we want to develop genuinely effective aging interventions for any of the aims mentioned above. Moreover, such science-based knowledge can help us sort out hyped claims and empty promises, from the actual progress and developments being made by hundreds of serious and committed scientists. The gist of the science of aging Biogerontology- the science of biological aging researchgained its scientific repute by the convergence of its evolutionary, physiological, biochemical, and molecular description and understanding. This realization inspired two of the pioneers of the field, Robin Holliday and Leonard Hayflick, to declare boldly that the problem of understanding aging has been solved [3, 4].

It did not mean that no further unravelling of the descriptive and mechanistic aspects of aging was required, and that all biological problems associated with old age were solved. It meant that a strong foundation and a framework for understanding aging has been developed, which should be the basis for further research, especially with respect to developing aging interventions for humans. One of the most important understandings to emerge from biogerontological research is that there are no aging-genes (gerontogenes), with a specific purpose/ function of causing aging [5, 6]. Aging is a slow and progressive impairment of physical function and fitness mainly due to the accumulation of unrepaired and unremoved molecular damage in cells, tissues, and organs. Therefore, whereas searching for a universal magic bullet to neutralize aging genes will be totally futile, the biochemical processes of damage repair and removal can be potential targets of intervention. A detailed description of age-related changes at all levels from the whole body to individual systems, organs, tissues, cells, and molecules is now available (Fig. 1).

This highly successful reductionistic description has also identified numerous genes, gene products, metabolites and pathways which correlate with aging, age-related diseases, and lifespan. Figure 1 (its upper part) gives some such examples, including telomeres, advanced glycation end-products (AGE), antioxidants, DNA methylation and others [7]. Hundreds more can, and will, be added to such an associative description of various pathways, processes, metabolites, and molecules with one or more phenotypes of aging. However, what such a correlative scheme does not show is a crucial fact that all aging changes do not occur in all individuals at the same rate and extent. Age-related changes are highly heterogenous at all levels from metabolites, molecules and cells to the whole body of an individual, and among individuals within a population [7].

Aging Matters | 15 |

THE SCIENCE OF AGING INTERVENTIONS

Individual whole body

Descriptions & associations

Systems Organs Tissues Cells

Proteasome

Stress responses

IGF DNA methylation Modified bases

Single target oriented interventions

Telomere

mTOR Anti-oxidants

Glycation

AGEs

Stimulators, Inhibitors, Stabilizers, Removers

Figure 1: Biogerontology: the science of aging research and interventions has achieved remarkable success in describing the phenomenon and phenotype of aging at various levels of organization all the way down to macromolecules and metabolites. The challenge now is to go upward from one or more molecular targets to higher levels of biological organization, (modified from [7]).

The practice of aging interventions The challenge now is to go upward from one or more molecular targets to higher levels of biological organization in order to reverse the age-related harmful changes, to rejuvenate, and to slow down the pace of future aging [7]. The lower part of the Figure 1 points to the molecular and

metabolic targets which are often the basis for numerous anti-aging interventions promoted commercially. Various stimulators, inhibitors, stabilizers and removers of some molecule, metabolite, process, or organelle, tested mostly in experimental model systems and sometimes tested in human as well, come under this category.

The general logic behind such extrapolations is that since a biochemical marker is decreased or increased with age, reverting that marker will reverse the overall phenotype to a healthy and youthful state. This, at best, is a simplistic and naïve approach that ignores what biology as such, and the science of aging, have come to understand so far.

The prevalent aging interventions can be categorized as follows: 1. Piecemeal remedies: The basic principle behind this approach is to “fix what is broke”; and such “fixing” methods range from cosmetics to the tissue/ organ repair or

| 16 | Aging Matters

transplantation, targeted treatments with stem cells, and rejuvenation with young blood/ plasma transfusion [810]. More recently, killing and removal of senescent cells by senolytic compounds is an

appealing approach [11, 12]. Although such interventions often have life-saving effects in acute situations, these benefits are often transient, limited and require recurring interventions [13, 14].

THE SCIENCE OF AGING INTERVENTIONS

2. Replenishment and supplementation: Replenishing the loss is the most widely used aging interventional strategy, tested mostly in animal model systems.

other metabolites is always harmful, and that these changes should be reset to some normal, youthful, and healthy levels.

of constant remodeling and adaptation for survival and health [7].

However, biogerontological studies have repeatedly shown that several ageinduced changes in the immune system, hormone levels and other proteins and enzymes are often the sign

Therefore, uncritical and over-supplementation with hormones, antioxidants and other nutritional replenishments may not provide the expected health benefits to an already healthy person [14, 15].

3. Holistic approaches: Biogerontologists are increasingly realizing that “single molecule, single target” oriented approaches for aging intervention are severely limited. This is because these approaches neglect the highly dynamic

interactive, and networking nature of the biological processes. Therefore, whole body level wholistic/ holistic approaches are being tested and developed as more rational aging interventions. In wholistic terms, food, physical activity, and socialmental engagement are

identified as the three pillars of human health, which are amenable to change and modification for health, survival, and longevity benefits. A common feature of these three pillars is the phenomenon of hormesis, as discussed below.

Hormesis and hormetins

production of free radicals, acids and aldehydes during the act of exercise, but provides the well-established whole-body health benefits later on [16, 17].

these are collectively termed as hormetins [18].

This approach is often based on the understanding that agerelated decline in the levels of enzymes, hormones or

Hormesis for health is defined as the life-supporting beneficial effects resulting from transient and repeated exposure to mild stress [16, 17]. Moderate physical exercise is the paradigm for hormesis, which initially increases the

Several such “stressors” have been identified with respect to their hormetic effects, and

Three main categories of hormetins are: physical, nutritional, and mental hormetins. Examples of some hormetins in each of the three categories are given in Table 1.

Hormetin category

Examples of potential hormetins

Physical hormetins

Thermal shock, (sauna, hot spring spa, cold bath), strength and stamina exercises, irradiation, hypergravity.

Nutritional hormetins

Whole spices or their active components, (curcumin, piperine, capsaicin, gingerine), polyphenols and flavonoids (resveratrol, allicin, epigallocatechin, quercetin), various herbs.

Mental hormetins

Chess, sudoku, focused attention, puzzles, social engagement.

Table 1: Categories and examples of mild stress-inducing hormetins for their health benefits

Aging Matters | 17 |

THE SCIENCE OF AGING INTERVENTIONS

The biochemical mechanism for the action of hormetins is the induction of one or more intracellular stress response pathways, which leads to the stimulation of intrinsic maintenance and repair mechanisms [19, 20]. An important aspect of hormesis is that a single stressor, such as heat, exercise, spices or fasting, can affect the overall health of the individual, and enhance other abilities including adaptability, cognition, immune response, memory, sexuality, resilience and robustness [17].

Hormetic way of life The science of aging research suggests that the best approach to aging interventions is to maintain health at all ages in a holistic manner. As mentioned earlier, food, physical activity and psychosocial engagement are the three pillars of health, which can be the main modes of healthy aging interventions. For this purpose, the practice of hormesis in daily life can be a very successful strategy.

A hormetic way of life involving the use of hormetins requires three conditions to be fulfilled: 1. Pleasure: since the central requirement for hormesis is the deliberate and repeated exposure to “stress of choice”, such an exposure must give pleasure. Whether it is physical and mental exercise, or it is mild stress-inducing nutritional components in the form of food or food supplements, the pleasure aspect of such choices should never be ignored.

2. Moderation: the requirement of hormesis through mild stress implies that the stress of choice should not be severe. Moderate exercise, (up to 70% of your maximal capacity), moderate fasting (8090% food intake instead of full-stomach intake) and avoiding complete mental exhaustion in psychosocial activities is essential for effective hormesis.

3. Variety: the effects of hormetins are best observed and achieved during the post-exposure period. It is very important for the hormetic practice that every exposure to a hormetin is followed by a recovery period during which time most of the health beneficial processes work. For an optimal hormetic way of life, it is important to vary the physical exercise regimen; vary and mix the consumption of spices and other nutritional hormetins; fast intermittently (once a week); and engage in a variety of mental and social activities.

| 18 | Aging Matters

3 Three pillars of health: 1. Food 2. Physical activity 3. Psycho-social engagements

In conclusion, it should be reminded that serious scientific research on aging is being done by hundreds of committed biogerontologists throughout the world. New discoveries with respect to the biological/ mechanistic aspects of aging, with the possibilities of future applications as aging interventions for humans, are being made regularly. Scientists will continue to develop technical, medicinal and lifestyle approaches that will help extended the lifespan and health span of all.

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SUPPLEMENTS AND NUTRIENTS IN CANCER PREVENTION AND THERAPY

SUPPLEMENTS AND NUTRIENTS IN CANCER PREVENTION AND THERAPY By Marios Kyriazis, M.D. When the subject of cancer comes up for discussion, we need to be mindful of these questions: 1. Are we talking about the prevention of all cancers? 2. Or are we talking of preventing only one type? 3. Or are we talking about curing an existing cancer? These are important questions because the approach would be different in each case. In the case of established cancer, it is necessary to find ways to work together with conventional medical therapies such as chemotherapy or radiotherapy. There are products and compounds which may help reduce the side-effects from these therapies and may help enhance the action of a particular chemotherapeutic agent. In the case of prevention, we may need to employ not only certain supplements or compounds, but also pay attention to the appropriate nutrition for each type of cancer, as well as general lifestyle measures | 20 | Aging Matters

that are already well known and accepted. Below is a discussion of some nutritional products or other compounds which may play a role in cancer prevention, and/ or may help improve the outcome of conventional anticancer therapies. As a personal note, I mention that I do not recommend selfhelp therapies for cancer if these are not under the direct supervision of a competent specialist. However, a wellinformed, open-minded, and knowledgeable physician may prove to be an invaluable asset in all aspects of cancer management. Resveratrol Let’s start the discussion with one of the most useful agents in health and aging, namely resveratrol. It is worth remembering that resveratrol is a natural polyphenol product, found in grapes

About the author Dr. Marios Kyriazis qualified as an MD from the University of Rome, Italy, and has worked as a clinician in acute medicine for 40 years in Cyprus, the USA and the UK. He is qualified Gerontologist with interest in the biology of aging and a member of the ‘Royal Society of Biology.’ He also has a post-graduate qualification in geriatric medicine from the ‘Royal College of Physicians,’ and an affiliated researcher with the University of Brussels on matters related to longevity.

and red wine, peanuts, and berries, (blueberries, mulberries, blackberries), as well as in supplement form. This, like some other agents that will be discussed below, is a pluripotent agent, meaning that it has multiple beneficial actions affecting several organs and processes in our body. It can affect the progression of several types of cancer, and it is considered as a chemo-preventative agent (it is a chemical that prevents cancerous changes). For example, it induces apoptosis, which is the orderly death of cancerous or otherwise damaged cells from our body, and this reduces the viability of cancerous cells in certain cancers, such as those of the cervix (1). Therefore, it is a potential candidate for use in the case of cervical cancer. But examples of its use in other cancers are numerous.

SUPPLEMENTS AND NUTRIENTS IN CANCER PREVENTION AND THERAPY

For instance, in a study of the effects of resveratrol on human colon cancer cells, it was shown that resveratrol prevents DNA damage, and increases apoptosis of the cancerous cells, while leaving healthy cells unharmed (2). The case of the benefits of resveratrol both on aging in general, and on cancer, is overwhelming. It is now well accepted by many scientists and physicians that resveratrol supplements should be used to reduce the risk of these two conditions. However, it is also important not to use this on its own, but to use it in association with other agents that have similar and

complementary actions. One of these agents is the dipeptide carnosine. Carnosine Carnosine (beta alanine, L-histidine), apart from its many pluripotent actions, may also enhance the action of certain drugs used in chemotherapy for cancer. For example, the chemotherapeutic drug cetuximab used in the treatment of many cancers, including colorectal cancer, may act more efficiently if it is used in association with carnosine. It works like this: glycolysis produces the byproduct methylglyoxal (MG), which promotes growth

of cancerous cells, and facilitates metastasis. It also interferes with the mammalian target of rapamycin 2 (mTORC2) that may result in resistance to treatment with cetuximab. However, carnosine which is a scavenger for methylglyoxal, reverses these adverse conditions, and leaves cetuximab free to exert its antineoplastic benefits (3). (See Figure 1). Another mechanism of carnosine is the suppression of angiogenesis. During cancer development, there is formation of new blood vessels which are needed for supplying nourishment to the growing cancer.

Figure 1: The schematic illustration depicts the action of carnosine in tumor volumes. As methylglyoxal (MG) concentration increases, the volume of cancerous cells in untreated (control) subjects increases up to a point and then drops. However, in carnosine treated subjects, this volume drops, and then increases again. It is therefore important to find the window of these beneficial effects of carnosine, which acts in a hormetic, dose-response manner. This confirms that it is not a simple matter of increasing the dose of compounds, expecting to find increasingly beneficial effects (that is to say, it is not a linear relationship). After a certain point, the compound in question may stop being effective. (See Suresh Rattan’s article about hormesis in this issue of the Aging Matters™ magazine).

Biphasic relationship between carnosine and MG 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 MG Carnosine

Control Aging Matters | 21 |

SUPPLEMENTS AND NUTRIENTS IN CANCER PREVENTION AND THERAPY

Using bladder cancer cells, researchers were able to show that carnosine modulates factors which promote angiogenesis, thus inhibiting the process of metastasis. This effect of carnosine, in some cases, was equivalent to that of cisplatin which is used routinely in cancer chemotherapy (4). Amygdalin (sometimes known as vitamin B17) The seeds of apricots, peaches and almonds are rich in this glycoside, which has both protective and detrimental effects in cancer. It is thus, a pluripotent modulator of physiological functions, and it is used by some physicians not only for general cancer protection but also against cough and fever. It protects against oxidative damage of human lymphocytes and reduces DNA damage (5). There is some research confirming the benefits of amygdalin on solid tumors such as those of the lungs,

kidneys, and bladder, whereas other research is inconclusive. Amygdalin works by releasing small amounts of cyanide which may kill cancer. It also induces apoptosis of cancerous cells and regulates the immune system (6). Research is still needed in this area, including research in establishing the right dose or its combined effects with another chemotherapeutic. Here again we see the principle of hormesis being involved, when low exposure to a poison (cyanide) can have benefits, where exposure to higher doses causes toxicity. It is relevant to mention here that research has shown a synergistic effect between amygdalin and zinc. A study of these combined effects on liver carcinoma cells (7), showed that whereas amygdalin on its own had “a strong anticancer activity”, the combination with zinc had an even better “highly significant” effect, by promoting apoptosis

of the cancerous cells. The researchers concluded that: “Amygdalin is a natural anticancer agent, which can be used for the treatment of hepatocellular carcinoma. It promotes apoptosis via the intrinsic cell death pathway (the mitochondria-initiated pathway) and cell cycle arrest at G/M. The potency of amygdalin in (liver cancer cells) treatment increased significantly by the addition of zinc.” Melatonin Changes in the circadian rhythm, i.e., an altered sleep-wake pattern due to melatonin dysfunction, has a well-studied association with cancer of the breast. Melatonin has anti-cancer effects on this and several other types of cancer (8). Its favorable effects were also discussed recently in pancreatic cancer (9), and specifically with melatonin’s ability to modulate apoptosis (Figure 2), inflammation and oxidative stress in the pancreas. We also know that men with high levels of melatonin have a muchreduced risk of developing prostate cancer, compared to men who have low levels of melatonin. One mechanism of this protective effect of melatonin is through the inhibition of MMP-13 which may increase the metastatic tendency of cancer (10).

| 22 | Aging Matters

SUPPLEMENTS AND NUTRIENTS IN CANCER PREVENTION AND THERAPY

What is MMP-13 (matrix metallopeptidase 13) and why is it important here? Well, the family of the matrix metalloproteinases (MMP) is a group of proteins which work in the extracellular space and take part in regulating tissue growth and development. MMP-13 is involved in the development (or not) of atherosclerosis, osteoarthritis, and rheumatoid arthritis, to name a few, and this depends on a very complicated chain of metabolic events. In any case, melatonin suppresses excessive activity of MMP13 and so it makes it more difficult for cancer to develop. There are over 2000 scientific papers studying the action of melatonin on human cancers, and most of these are listed in Medline. Something that can be relevant in the case of radiotherapy and melatonin, is the case of ionizing radiation. Although ionizing radiation is used in radiotherapy, it is known that it can cause oxidative imbalance which can have negative consequences on healthy cells too. In this sense, scientists studied the effects of melatonin with respect to controlling excessive oxidative damage during radiotherapy. In this study, in addition to melatonin, vitamin D was also associated with protective, antioxidant effects (11). This is a complex area, because a balance must be found between excessive protection, (which can also unwittingly

Melatonin

Bc1-2

Bax

4 Cyt C

Apoptosis

Caspase-3 Caspase-3

Figure 2: How melatonin affects apoptosis: It regulates the balance between apoptotic factors Bcl-2 and Bax, and this activates a chain of events which release Caspase-3 from the mitochondria, resulting in the death of the damaged cell.

protect cancerous cells), and limited protection, (which can cause damage not only to cancerous cells, but also to healthy cells). This example is mentioned here as a suggestion supporting the generally beneficial effects of melatonin. It also relevant to mention that it crosses the blood-brain barrier, and so it can also be used in other chronic degenerative conditions such as Alzheimer’s dementia and Parkinson’s disease. But melatonin, to work fully, has certain peculiarities. First, although it can be taken at any time during the day and night, it works better when the individual is in complete darkness, something that can be achieved during sleep time. Studies show that under complete darkness, melatonin can suppress cancerous growth. Its

secretion is inhibited during exposure to light, and logically, its benefits are blocked too. For more details see here: https://aging-matters.com/ melatonin-stops-cancer/ Second, there is the issue of the dose. In cancer experiments, very high doses of melatonin were used. For example, a leading melatonin expert, Dr. Walter Pierpaoli, has used daily dosages from as low as 0.1 mg to a whopping 200 mg a day without side-effects. Others have used a relatively more conservative dose of 100 mg at night. Coriolus versicolor There are several studies regarding a fungus used in Asia, (China, Japan), and its ability to influence cancer development. Aging Matters | 23 |

SUPPLEMENTS AND NUTRIENTS IN CANCER PREVENTION AND THERAPY

from coriolus also have an immune-boosting effect, which, in association with the other actions of these polysaccharides, may translate into an overall benefit in cancer development (14). Phosphatidylcholine Above: Cariolus versicolor fungus

Coriolus versicolor is an edible medicinal mushroom, also known as Trametes versicolor. It contains polysaccharides, which have been claimed to have cancer-inhibiting properties. Here, it is relevant to mention that cancer cells develop within a favorable (to them) microenvironment where the concentration of nutrients, immune function, blood flow and many other factors is in perfect balance. When this balance is disrupted, then the development of cancer is inhibited. In this respect, it was found that coriolus extracts interfere with immune and inflammation factors within this microenvironment, and so they slow down the growth and development of cancer (12). In addition, polysaccharides derived from coriolus are known to reduce oxidative damage and modulate apoptosis of melanoma cells, and this suggests that the extracts may be useful in other cancers too (13). In general, it is known that polysaccharides | 24 | Aging Matters

In several tumors, including cervical cancer, there are alterations in the composition of cell membrane lipids, when compared to the physiological situation. When cancer cells develop, they depend on metabolic pathways to synthesize complex lipids, which serve as protectors of their cell membrane. It is known that phosphatidylcholine which is the major phospholipid component of such cell membranes, can play a role in the growth of cancer, and this can happen when the phospholipid metabolism is disrupted. In a study, it was found that phosphatidylcholine, as well as some other lipids, show significant changes both in early cancerous changes and in full-blown cervical cancer, when compared to healthy controls. Therefore, lipid profiling can be a useful method for monitoring the development of cancer in this example. In addition, a healthy lipid balance plays a role in chemoresistance, in other words, in the resistance of the cancer against chemotherapy.

So, it is important to maintain a normal, healthy status when it comes to phosphatidylcholine metabolism (15). Conclusion Prevention or treatment of cancer does not only depend on lifestyle measures or physician-only prescribed drugs. Certain nutritional supplements, compounds or agents can also be used to support and complement existing approaches. This is a specialized subject that requires open mind, knowledge, expertise, and a desire to explore other possibilities. There is no place for complacency or for not seeking expert advice which must be tailored to each specific individual. Research is continuing and aims to clarify some controversies that may exist, or to expand on the mechanisms of action of these and many other compounds. We must continue to inform ourselves about these latest developments to devise the best possible action plan for reducing the risk of cancer and aging in general.

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NAD FOR LONGER LIFESPANS

NAD FOR LONGER LIFESPANS By Will Block To live well and flourish as human beings, we need lots of nicotinamide adenine dinucleotide (NAD), a nicotinic-based molecule found within nearly every cell in the human body (see figure 1). However, as we age, we lose this all-important molecule largely from the decline of proper sirtuin activity. [1] The longevity genes, called ‘sirtuins’, are named after the yeast SIR2 gene, the first sirtuin to be discovered. Sirtuins are NAD-utilizing enzymes and much research has been done into how the body controls sirtuins. Sirtuins are thought to be a primary reason our bodies develop diseases when we are old, but not when we are young. O NH2

P O O

OH OH

NH2

N O

P O O-

N N

LEXICON

DESCRIPTION

AlphaTOR inhibitor

A statin

AMPK

(AMP-activated protein kinase) is known as a master regulator of metabolism.

Exercise

Is the application of stress to our bodies.

Fisulin

The first SIRT1-activating compound, or STAC, was a polyphenol.

Flourish

Flourish improves and make up the loss due to aging.

FOXO3

A variant has been shown to related to longevity in humans.

NAMPT

The gene in our bodies that recycles NAD.

NAD (nicotinamide adenine dinucleotide)

Used by over five hundred different enzymes and its loss results in the decline in sirtuin activity.

Nicotinamide riboside (NR)

Converted to NMN.

Nicotinamide mononucleotide (NMN)

Pyrazinamidase/ nicotinamidase 1 (PNC1)

Boosts NAD production.

Resveratrol

A type of natural phenol, produced in certain plants when under attack by pathogens, such as bacteria or fungi.

Sirtuin genes

Named after the yeast SIR2 gene, the first one to be discovered.

OH OH Figure 1: The chemical formula of NAD

NaAD

NAD

| 26 | Aging Matters

NADP

ADP-ribose QA

NaMN

NMN

ADP-ribosyl

NAD FOR LONGER LIFESPANS

Sirtuins: NAD-Utilizing Enzymes Shin-ichiro Imai, an associate of Dr. David Sinclair when he was at MIT, and now a professor at Washington University, discovered much of the valuable material about sirtuins.

Hidden within the sometimes-confusing way scientists talk about science are several repeating themes. Among these are low energy sensors transcription errors. Plus, additional NAD and sirtuin boosters, stress resistance, and longevity factors.

Principally, that they are NADutilizing enzymes. He also does research into how the body controls sirtuins.

The mice in Sinclair’s study were 20 months old, roughly the equivalent of a 65-yearold human.

David Sinclair, PhD, AO is best known for his work on genes and small molecules that delay aging, including the sirtuin genes, resveratrol, and NAD precursors. He is the author of a new book on aging published in 2019 Lifespan: Why We Age and Why We Don’t Have To.

The researchers had fed them a molecule intended to boost the levels of NAD, which they believed would increase the activity of sirtuins. If the mice were developing a ‘running addiction,’ that would be a very good sign.

Ex Figure 2: Dr. David Sinclair’s book: Why we age and why we don’t have to.

Restriction in Mice Sinclair and his lab at Harvard discovered that when calories are restricted in mice, yeast lifespan is extended by turning up genes that recycle NAD, thereby giving the sirtuins a growth boost. (See figure 3).

Why? One of the key findings of a lab study, published in 2018, was that when treated with an NAD-boosting molecule that activated endothelial cells that line up when treated with an NAD-boosting molecule that activated the SIRT1 enzyme, the elderly mice’s endothelial cells, which line the blood vessels, were pushing their way into areas of the muscle that weren't getting very much blood flow. Scientists still don’t know everything about why this happens. They don’t know what sort of molecules will work best for activating sirtuins or the correct dose. Hundreds of different NAD precursors have been synthesized, and there are clinical trials in

progress to answer that question and more. Exercise is the Application of Stress Exercise, by definition, is the application of stress to our bodies. It raises NAD levels, which in turn activates the survival network, which turns up energy production and forces muscles to grow extra oxygen-carrying capillaries. What happens on the other side of the thermostat? The picture is a bit less clear, but we have some promising leads from the laboratory yeast S. cerevisiae. A seemingly lowly, singlecelled yeast with a sweet tooth (its name means ‘sugar-loving’) to its rightful place as one of the world’s most important research organisms. We know from work in Sinclair’s lab that raising the temperature of yeast—from 30°C to 37°C, just below the limits of what those single-celled organisms can sustain—turns on the pyrazinamidase/ nicotinamidase 1 (PNC1) gene and boosts their NAD production, so their sirtuin proteins can work that much harder. What’s fascinating is not so much that these temperature-stressed cells lived 30 percent longer but that the mechanism is the same as that evoked by calorie restriction. Aging Matters | 27 |

NAD FOR LONGER LIFESPANS

NAMPT, the Gene in our Bodies that Recycles NAD Sauna studies show that temporary heat exposure may be good for us. But they do not tell us why. If yeast is any guide, more knowledge of NAMPT, the gene in our bodies that recycles NAD, may be useful. NAMPT is turned on by a variety of adversity triggers, including fasting and exercise, which makes more NAD so the sirtuins can work hard at making us healthier. Sinclair et al have never tested if NAMPT is turned on by heat, but that could be done by others. Either way, one thing is clear: it does us little good to spend our entire lives in the thermoneutral zone. Our genes didn’t evolve for a life of pampered comfort. A little stress to induce hormesis occasionally may go a long way. But dealing with biological adversity is one thing. Over-whelming genetic damage is another. A bit of adversity or cellular stress is good for our epigenome because it stimulates our longevity genes. If this sounds chaotic, it is. Nevertheless, we need this chaos for order to emerge. Without it, the molecules that must come together to sustain life would not find each other, and they would not fuse. | 28 | Aging Matters

The human sirtuin enzyme called SIRT1 serves as a good example. Precise vibrating sockets on SIRT1 simultaneously clasp onto an NAD molecule and the protein it wants to strip the acetyls from a histone or a special molecule. The two captured molecules immediately lock together, just before SIRT1 rips them apart in a different way, producing vitamin B3 and acetylated adenine ribose, waste products that are recycled back to NAD. Metformin Impacts Many Diseases Many life extension enthusiasts are now dosing with the diabetic drug metformin. The beauty of metformin is that it KOs many of the diseases of aging. As does AMPK (AMP-activated protein kinase), a master regulator of metabolism. Cells activate AMPK when they are running low on energy, and AMPK is activated in tissues throughout the body following exercise or during calorie restriction. AMPK makes more NAD and turns on sirtuins and other defenses that act against aging engaging the survival circuit upstream of these conditions, ostensibly slowing the loss of epigenetic information and keeping metabolism in check, so all organs stay younger and healthier.

When they are activated, either by low-calorie or low-amino-acid diets, or by exercise, organisms become healthier, disease resistant, and longer lived. Tweaking Rapamycin, Metformin, Resveratrol, and NAD Pathways Molecules that tweak these pathways, such as rapamycin, metformin, resveratrol, and NAD boosters can mimic the benefits of low-calorie diets and exercise and extend the lifespan of diverse organisms. By engaging our bodies’ survival mechanisms in the absence of real adversity, will we push our lifespans far beyond what we can today? And what will be the best way to do this? Could it be a souped-up AMPK activator? An alphaTOR inhibitor? The first SIRT1activating compound, or STAC, was a polyphenol called fisetin. Or a combination of them with intermittent fasting and high-intensity interval training? The potential permutations are virtually endless. Another STAC is NAD, sometimes written as NAD+. NAD has an advantage over other STACs because it boosts the activity of all seven sirtuins. NAD was discovered in the early twentieth century as an alcoholic fermentation enhancer. That was unexpected: if it hadn’t had the potential to improve the way we make booze;

NAD FOR LONGER LIFESPANS

scientists might not have been so charmed by it. Curing the Canine Equivalent of Pellagra Instead, they worked on it for decades, and in 1938 NAD was able to cure black tongue disease in dogs, the canine equivalent of pellagra. It turned out that NAD is a product of the vitamin niacin, a severe lack of which causes inflamed skin, diarrhea, dementia, skin sores, and ultimately death. And because NAD is used by over five hundred different enzymes, without any NAD, we’d be dead in O thirty seconds. -

By theO1960s, however, + O P O had concluded researchers N O that all the interesting research on NAD had been done.

Without sufficient NAD, the sirtuins don’t work efficiently: they can’t remove the acetyl groups from histones, they can’t silence genes, and they can’t extend lifespan. And we sure wouldn’t have seen the lifespan-extending impact of the activator resveratrol! Sinclair and others also noticed that NAD levels decrease with age throughout the body, in the brain, blood, muscle, immune cells, pancreas, skin, and even the endothelial cells that coat the inside of microscopic blood vessels.

But because it’s so central to so many fundamental cellular processes, no researchers in the twentieth century NH2 had any interest in testing the effects of boosting levels of NAD.

“Bad stuff will happen if you mess with NAD,” they OH OH NH 2 For decades to come, NAD thought. But not even having was simply a housekeeping tried to manipulate it, they N N chemical that teenage didn’t really know what O O Pstudents biology hadNto would happen if they did. The N O learn about—with all the benefit of working with yeast, O enthusiasm of a teenager though, is that the worst-case doing housekeeping. scenario in any experiment is a yeast massacre. OH OH That all changed in the 1990s, when we began to realize that NAD wasn’t just keeping NaAD things running; it was a central regulator of many major biological processes, NMN QA NaMN including aging and disease. O

That’s because Shin-ichiro Imai and Lenny Guarente showed that NAD acts as fuel for sirtuins.

There was little risk in looking to boost NAD in yeast. This’s why Sinclair’s lab members worked on this. The easiest way was to identify the genes that make NAD in yeast. They first discovered a gene called PNC1, which turns vitamin B3 into NAD. That led the lab to try boosting PNC1 by introducing four extra copies of it into the yeast cells, giving them five copies in total. Living Longer with Sirtuins Those yeast cells lived 50 percent longer than normal, but not if the lab removed the SIR2 gene. The cells were making extra NAD, and the sirtuin survival circuit was being engaged! Could Sinclair’s lab do this in humans? Theoretically, yes. They had already established that they had the technology to do this, using viruses to deliver the human equivalent of the PNC1 gene called NAMPT.

NAD

NADP ADP-ribose Nam

ADP-ribosyl transfer

NR Trp

Figure 3: NAD cycle.

Aging Matters | 29 |

NH2

Trp O

N+

NAD FOR LONGER LIFESPANS

OH O

O HO HO

But a lot of people haven’t been content to wait for these studies, which can take years to play out.

NH2

N+

NH2

-O

O P

N+

NAD Boosters

O HO

NH2 Figure 4: The NAD boosters, from left to right, nicotinamide riboside and nicotinamide mononucleotide.

But turning humans into O -O transgenic organisms P requires more paperwork and considerably more HO knowledge about safety—for the stakes are higher than a yeast massacre. That’s why the researchers once again began searching for safe molecules that would achieve the same result. Another Route Charles Brenner, who is now the head of biochemistry at the University of Iowa, discovered in 2004 that a form of vitamin B3 called nicotinamide riboside (NR), is a vital precursor of NAD. He later found that NR, which is found in trace levels in milk, can extend the lifespan of yeast cells by boosting NAD and increasing the activity of Sir2. Once a rare chemical, NR is now sold by vast amounts each month as a nutraceutical. In the body, NR is converted into NMN, which is then converted into NAD. | 30 | Aging Matters

And that has given us some interesting leads about where these molecules, or ones like them, might take us.

Give an animal a drink with O in it,Nand + NR or NMN the levels of NAD in its body go O up about 25 percent over the next couple of hours, about HO OH the same as if it had been fasting or exercising a great deal. Sinclair’s friend from the Guarente lab Shin-ichiro Imai demonstrated in 2011 that NMN could treat the symptoms of type-2 diabetes in old mice by restoring NAD levels. Then researchers in Sinclair’s lab at Harvard showed we could make the mitochondria in old mice function just like mitochondria in young mice after just a week of NMN injections. Human studies with NAD boosters are ongoing. So far, there has been no toxicity, not even a hint of it. Studies to test its effectiveness in muscle and neurological diseases are in progress or about to begin, followed by super-NADboosting molecules that are a couple of years behind them in development.

We know that NAD boosters (see figure 4) are an effective treatment for a wide variety of ailments in mice and that they extend their lifespan even when given late in life. We know that emerging research strongly suggests they could have a similar, if not duplicative, effect on human health. But a trial in 2018 to test whether an NAD booster could restore the fertility of old horses was successful, surprising the skeptical supervising veterinarian. These anecdotal reports of restored menstruation and fertile horses are early but interesting indicators that NAD boosters might restore failing or failed ovaries. We also must remember what NMN does: it boosts NAD, and this boosts the activity of the SIRT2 enzyme, a human form of yeast Sir2 found in the cytoplasm. All therefore are early indicators of restored ovarian function in humans, anecdotal as they may be, are so fascinating.

NAD FOR LONGER LIFESPANS

If true, the mechanisms that work to prolong life bolster the case for NAD boosters. But the early indicators of the safety and effectiveness of the molecules in yeast, worms, and rodents are such that many people have already begun their own private human experiments. Come What May By engaging our bodies’ survival mechanisms in the absence of real adversity, will we push our lifespans far beyond what we can today? And what will be the best way to do this? Could it be a souped-up AMPK activator? An alphaTOR inhibitor? The first SIRT1activating compound, or STAC. Or a combination of them with intermittent fasting and high-intensity interval training? The potential permutations are virtually endless. But as mice age, and possibly as we do as well, these sirtuins become scattered all over the genome, having been recruited away to repair DNA breaks elsewhere, and many of them never find their way home. This loss is exacerbated by a drop in NAD levels—the same thing we first saw in old yeast. Without sirtuins to spool the chromatin and silence the transposon DNA, cells start to transcribe these endogenous viruses.

Silencing the Jumping Genes We may eventually find out that as NAD levels decline with age, sirtuins are rendered unable to silence retrotransposon DNA. Perhaps one day, safe antiretroviral drugs or NAD boosters will be used to keep these jumping genes silent. Today, many of Sinclair’s colleagues are just as optimistic, even though they will not openly admit it. I’d bet that about a third of them take metformin or an NAD booster. A few of them may even take doses of rapamycin intermittently.

And on top of what we already know about metformin, NAD boosters, rapalogs, and senolytics every day the odds increase. In time, even more effective molecule or gene therapy will no doubt be discovered, as brilliant researchers around the world join the global fight to treat aging, the mother of all diseases. In the meantime, we all seek out the best that is available today.

Nicotinamide riboside, or NR, is converted to NMN, so whilst some people take NR instead of NMN, it is possibly not as effective as NMN. Studies are not always favorable to its use. Cheaper still are niacin and nicotinamide, but they don’t raise NAD levels as efficiently as NMN and NR do.

Dr. David Sinclair is the scientist who has bought NAD to the attention of the world.

Some scientists have suggested NAD boosters could be taken with a compound that provides cells with methyl groups, such as trimethylglycine, also known as betaine or methylfolate. Conceptually, this makes sense—the “N” in NR and NMN stands for nicotinamide, a version of vitamin B3 that the body methylates and excretes in urine when it is in excess.

References: For more information scan this QR code

Aging Matters | 31 |

NATURAL ANTIVIRALS

NATURAL ANTIVIRAL SOLUTIONS By Will Block In these troubled times, we have looked to nature to discover some agents that can be considered to be natural antivirals. In so doing, we hope that putting them into our diets, or utilizing them as supplements can be beneficial. The following is a listing of those agents and their validity. BHT (butylated hydroxytoluene) Some ‘all-natural advocates,’ reject BHT to a false belief that it is synthetic. But this is not true! According to a whale study (1), BHT is naturally found in the food of some baleen whales! A few years ago, scientific researchers found that this potent antioxidant is naturally synthesized in four freshwater phytoplankton, including a green alga and three cyanobacteria. Its purpose in these organisms is to potently prevent free radical damage. Phytoplankton are generally regarded as innocent and health-promoting. After all, they are eaten by krill (a type of shrimp, see figure 1), which in turn provide dinner for baleen whales. The name of the antioxidant found in phytoplankton is butylated hydroxytoluene, otherwise known as BHT. It may be disliked by some, but it is loved by others because of its biochemical and beneficial properties. | 32 | Aging Matters

Herpes Virus, and Cold Sores Most photosynthetic organisms, (including phytoplankton) are exposed to a combination of light and high oxygen concentrations, leading to the formation of free radicals and other strong oxidizing agents. Nevertheless, photoplankton seldom suffer from serious photodynamic and DNA damage in-vivo, suggesting that their cells contain protective antioxidative mechanisms and other protective compounds. Could it be the BHT?

BHT is an FDA-approved food additive for certain salad and cooking oils. It has been found to be an effective natural treatment for several viral conditions including hepatitis B, hepatitis C, the Epstein Barr virus, the herpes virus, and cold sores. (Reference: Wipe out herpes with BHT, John Mann & Steven Wm Fowkes, Megahealth Society Publishing). Shiitake: Food and Medicine Lentinula edodes, also known as Shiitake mushroom, has

Figure 1: A krill, which is a popular food with the baleen whales.

NATURAL ANTIVIRALS

of viral adsorption was not significant. The results allowed the researchers to conclude that AqE, EtOHE and LeP act on the initial processes of the replication of both strains of virus. The time-of-addition assay was performed at the times -2, -1, 0, 1, and 2 hours of the infection.

been utilized as food, as well as a medicinal plant. Moreover, compounds isolated from its mycelium and fruiting body have shown several therapeutic properties. The aim of one study (2) was to determine the antiviral activity of aqueous (AqE) and ethanol (EtOHE) extracts and a polysaccharide (LeP) from Lentinula edodes in the replication of poliovirus type 1 (PV-1) and bovine herpes virus type 1 (BoHV-1). The time-of-addition assay was performed at the times -2, -1, 0, 1 and 2 hours of the infection. The virucidal activity and the inhibition of viral adsorption were also evaluated. Plaque assay was used to monitor antiviral activity throughout the study. The AqE and LeP were more effective when added at 0 hours of infection, However, EtOHE was more effective at the times 1 hour and 2 hours of the infection. AqE, EtOHE, and LeP showed low virucidal activity, and the inhibition

The virucidal activity and the inhibition of viral adsorption were also evaluated. Plaque assay was used to monitor antiviral activity throughout it. In this study (3), shiitake, by hot-water extraction and ethanol precipitation, was fractionated by column chromatography, resulting in six polysaccharide fractions. Among these fractions, three were shown to stimulate the functional activation of macrophages including NO production cytokine expression and phagocytosis. Reishi: Mushroom of Immortality The use of the Reishi mushroom (Ganoderma lucidum) was first recorded over 2,000 years ago. Reishi was frequently referred to as the “Mushroom of Immortality” in ancient texts. Around 200–250 CE, the ‘Divine Farmer’s Classic of Pharmaceutics’ categorized different varieties of mushrooms based on which part of the body they benefited.

Proponents of Reishi claim it is especially good at modifying the immune system by increasing it when weakened or lowering it when it is too active. Reishi mushrooms are considered to contain natural antiviral, antibacterial and antifungal substances thanks to the active compounds that they contain. For example, aside from relieving allergies and triterpenes, they offer protection against microbial, viral, and fungal infections. Gypsy Mushroom Viral infections are amongst the most common diseases affecting people worldwide. New viruses are emerging all the time and presently we have a limited number of antivirals to combat viral diseases. Yet, Fungi represent a vast source of bioactive molecules, which could potentially be used as antivirals. Researchers have summarized the current knowledge of fungi as producers of antiviral compounds and discuss their potential applications. They have what is known about the molecular mechanisms and actual targets. Furthermore, the scientists highlight the importance of accurate fungal species identification on antiviral and other natural products studies. (4)

Aging Matters | 33 |

NATURAL ANTIVIRALS

Immunomodulators and antiviral properties of this mushroom could be a potential source to overcome the current pandemic outbreak. Dengue Virus Dengue is a mosquitoborne viral infection that has become a major public health concern worldwide. Presently, there is no specific vaccine or treatment available for dengue viral infection. To look for treatments, Lignosus rhinocerotis, Pleurotus giganteus, Hericium erinaceus, Schizophyllum commune, and Ganoderma lucidum were selected for evaluation of their in-vitro anti-dengue virus serotype 2 (DENV-2) activities. Hot aqueous extracts (HAEs), ethanol extracts (EEs), hexane soluble extracts (HSEs), ethyl acetate soluble extracts (ESEs), and aqueous soluble extracts (ASEs) were

prepared from the selected mushrooms. The cytotoxic effects of the extracts were evaluated by the MTT assay. The anti-DENV-2 activities of the extracts were evaluated in three different assays: simultaneous, attachment, and penetration assays were performed using plaque reduction assays and RT-qPCR assays [see ThermoFisher Scientific]. The effect of the addition of time on viral replication was assessed by the time of addition assay, and a virucidal assay was carried out to evaluate the direct effect of each mushroom extract on DENV-2. The chemical composition of glucans, and the protein and phenolic acid contents in the extracts were estimated as well. The researchers found that the HAEs and ASEs of L. rhinocerotis, P. giganteus, H. erinaceus, and S. commune

were the least toxic to Vero cells and showed very prominent anti-DENV2 activity. The 50% inhibitory concentration (IC50) values of the ASEs ranged between 399.2-637.9 μg/ml, while for the HAEs the range was 312.9-680.6 μg/ml during simultaneous treatment. Significant anti-dengue activity was also detected in the penetration assay of ASEs (IC50: 226.3-315.4 μg/ml) and HAEs (IC50: 943.1-2080.2 μg/ ml). Similarly, the researchers observed a marked reduction in the expression levels of the ENV and NS5 genes in the simultaneous and penetration assays of the ASEs and HAEs. Time-of-addition experiments showed that the highest percent of anti-DENV2 activity was observed when the mushroom extracts were added immediately after virus adsorption. None of the extracts exhibited the virucidal effect. Chemical composition analysis showed that the major components in the mushroom HAEs and ASEs were glucan (beta D-glucan) and proteins, however, there was no significant correlation between the anti-dengue activity and the concentration of glucans and proteins. These findings demonstrated the potential of mushroom extracts as anti-dengue therapeutic agents with less toxic effects. (5)

Figure 2: Dengue Virus

| 34 | Aging Matters

NATURAL ANTIVIRALS

In another study (6), researchers have summarized the current knowledge of fungi as producers of antiviral compounds and discuss their potential applications. They have investigated how the antiviral action has been assessed and what is known about the molecular mechanisms and actual targets. Furthermore, they highlight the importance of accurate fungal species identification on antiviral and other natural products studies. The absence of commercialized/ fully approved vaccines and antiviral agents against dengue has made the disease a major health concern around the world. With the current dengue virus transmission rate and incidences, the development of antiviral drugs is of vital need. The aim of this project was to evaluate the possibility of developing a local medicinal plant. A cocktail of aqueous and methanolic extracts were prepared from four species of Phyllanthus (P.amarus, P.niruri, P.urinaria, and P.watsonii) and their polyphenolic compounds were identified via HPLC and LC-MS/MS analysis. MTS assay was then carried out to determine the maximal non-toxic dose (MNTD) of

the extracts, followed by screening of the in vitro antiviral activity of aqueous cocktail extracts against DENV2 by means of time-ofaddition (pre-simultaneous, and post-) using RT-qPCR. The differentially expressed proteins in the treated and infected cells were analyzed with two-dimensional gel electrophoresis experiments. Several active compounds including gallic acid, geraniin, syringin, and corilagen have been identified and tested (7). The MNTD of both aqueous and methanolic extracts on Vero cells were 250.0 μg/ml and 15.63 μg/ml respectively. Phyllanthus showed the strongest inhibitory activity against DENV2 with more than 90% of virus reduction in simultaneous treatment. Twodimensional analysis revealed significantly altered levels of thirteen proteins, which were successfully identified by tandem MS (MS/MS). These altered proteins were involved in several biological processes, including viral entry, viral transcription and translation regulations, cytoskeletal assembly, and cellular metabolisms. Cranberry Juice Studies were undertaken to investigate the antiviral effects of comestible juices, especially cranberry juice, on non-related viral species. After exposure of bacteriophage T2

to a commercially available cranberry (Vaccinium macrocarpon) juice cocktail (CJ), virus infectivity titer was no longer detectible. After a 60-min exposure to orange (OJ) and grapefruit juices (GJ), phage infectivity was reduced to 25-35% of control, respectively. Similar data were observed for the bacteriophage T4. CJ inactivation of phage T4 was rapid, dose-dependent, and occurred at either 4= or 23-degrees C. Neither pH nor differences in sugar/ carbohydrate levels among the juices may be ascribed to the recognized antiviral effects. Further studies were performed to identify the occurrence of antiviral activity by CJ to a mammalian enteric virus. The treatment of the simian rotavirus SA-11 with a 20% CJ suspension was sufficient to inhibit hemagglutination.

Aging Matters | 35 |

NATURAL ANTIVIRALS

Under scanning and transmission electron microscopy, CJ was observed to inhibit the adsorption of phage T4 to its bacterial host cells and prevented the replication of rotavirus in its monkey kidney (MA-104) host cells, respectively.

immune-activating effects resides in the metabolically fermented substrate.

The data suggest, for the first time, a non-specific antiviral effect towards unrelated viral species (viz., bacteriophages T2 and T4 and the simian rotavirus SA-11) by a commercially available cranberry fruit juice drink. (8)

The initial substrate served as a control. Aqueous fractions were extracted and passed through 0.22-μm filters. The remaining solids were passed through homogenization spin columns without filtration.

Turkey Tail Mushrooms The medicinal mushroom Trametes versicolor (Tv, Turkey Tail) is often prepared for consumption as a powder from the fungal mycelium and the fermented substrate on which it grew. The goal for this study (9) was to evaluate the immunemodulating properties of the mycelium versus the fermented substrate, to document whether an important part of the

Tv mycelium was cultured on rice flour. The mycelium and the fermented substrate were mechanically separated, dried, and milled.

The aqueous and solid fractions of the initial substrate (IS), the fermented substrate (FS), and the Trametes versicolor mycelium (TvM) were tested for immune-activating and modulating activities on human peripheral blood mononuclear cell cultures, to examine expression of the CD69 activation marker on lymphocytes versus monocytes, and on the T, NKT, and NK lymphocyte subsets. Culture supernatants were tested for cytokines using Luminex arrays.

Both aqueous and solid fractions of TvM triggered robust induction of CD69 on lymphocytes and monocytes, whereas FS only triggered minor induction of CD69, and IS had no activating effect. The aqueous extract of TvM had stronger activating effects than the solid fraction. In contrast, the solid fraction of IS triggered a reduction in CD69, below levels on untreated cells. Both aqueous and solid fractions of FS triggered large and dose-dependent increases in immuneactivating pro-inflammatory cytokines (IL-2, IL-6), anti-inflammatory cytokines Interleukin-1 receptor antagonist (IL-1ra) and Interleukin-10 (IL-10), anti-viral cytokines interferon-gamma (IFN-γ) and Macrophage Inflammatory Protein-alpha (MIP-1α), as well as Granulocyte-Colony Stimulating Factor (G-CSF) and Interleukin-8 (IL-8). TvM triggered more modest cytokine increases. The aqueous extract of IS showed no effects, whereas the solid fraction showed modest effects on induction of cytokines and growth factors. The results demonstrated that the immune-activating bioactivity of a mycelialbased medicinal mushroom preparation is a combination of the mycelium itself (including insoluble betaglucans, and water-soluble components), and the highly

| 36 | Aging Matters

NATURAL ANTIVIRALS

bioactive, metabolically fermented substrate, not present in the initial substrate.

damaging the protective layer of the viral cell, in turn making the virus vulnerable to the immune system, which may result in preventing the virus from multiplying and causing outbreaks.

Summary BHT blended with medical mushrooms known for their antiviral properties is of interest. BHT is believed to work against viruses by potentially

ViralPro

™

Whilst mushrooms such as Shiitake, Reishi, Gypsy, and Turkey Tail act in other ways to destroy and eliminate viruses. This combination is found in ViralPro™.

References: For more information scan this QR code

30 capsules

$21.99 save $4.99 with voucher code AMVIRALP5 valid until October 31, 2021 Formula: each capsule contains: BHT....................................................250mg* Shiitake mushroom..............................50mg* Turkey tail mushroom..........................50mg* Reishi mushroom.................................50mg* Rozites caperata (gypsy) mushrooms.............................50mg* *% Daily Value not established

Suitable for Vegetarians

www.antiaging-systems.com

Credit card payments available

Aging Matters | 37 |

SPOTLIGHT 1ST LINE™ - the first line of immunity Professor Paul Clayton reported in the Aging Matters magazine No1, 2012, that ‘the age of antibiotics is coming to an end.’ This has been a concern for some time as antibiotics becomes less effective and can’t be relied upon as they were in the past. What’s more, antibiotics do not destroy viruses, and when it comes to effective antivirals there are very few choices indeed. OSCN A British chemist by the name of Richard Steed was concerned how chlorine was being in foodas it is sprayed onto salads. It kept the vegetables free of bacteria, but it is hardly a healthy option for the consumers. He investigated nature and found that oxythiocynate ions, otherwise known as OSCN

are present in tears, saliva and mother’s milk and appear to destroy many pathogens including viruses, since OSCNs are literally the first line of immune defence. Thereafter, he created the world’s first supplement containing OSCN molecules. Soon it was realised that they also had massive health implications. An OSCN kit An OSCN kit OSCNs have a very short half-life, something like 30 minutes, which is why you have never seen them presented in a supplement before. But 1ST LINE™ is different because it is a kit containing the active and 3 enzymes to make up the supplement in a glass of water for consumption straight away. It is easy to use, simply add

the 4 agents in the right order (marked 1-2-3-4), stir and drink. 1st Line™ has no smell or flavor. Doing so creates 25 mg of OSCN, the equivalent to what a healthy body produces in a day. How to use Obviously, there are a plethora of infections out there, but on a simple level take a 1st Line™ dose at the first sign of infection and repeat the dose for a day or two afterward, as necessary. For maintenance, some individuals like to take one dose of 1st Line every month in order to keep the ‘body burdens’ low.

ACF228® - the ultimate free radical scavenger The ACF abbreviation means ‘antioxidant complete formula’ and 228 because it was Dr. Richard Lippman’s 228th formula that proved to be very effective. Dr. Richard Lippman was nominated for the Nobel Prize in medicine for his work in measuring free radical activity in-vivo; in other words what happens within the human body. The result of that work led to the incredibly comprehensive formula known as ACF228®. Free radicals Free radicals are unstable molecules that can be created ‘naturally’ within the body and they can ‘disorganise’ healthy cells by crashing around- a bit like bumper cars at a fayre. The | 38 | Aging Matters

free radical theory of aging was first proposed by Professor Denham Harman in the late 1950s and it helps to explain the degenerative processes that occur during aging.

synergistic agents that have been designed to help neutralise every level of free radicals, no other single product has been in-vivo designed- each ACF228® capsule contains:

Hierarchy There are several levels of free radicals, and the worst of them are the superoxide and the hydroxyl free radicals. Neutralisation of ‘higher level’ free radicals can create a plethora of lower level free radicals, so it is important to try and impact every stage, but of course to particularly target the most destructive free radicals.

Ingredients

Potency In the ACF228® formula there are numerous unique molecules like catalase and especially NDGA within ACF228®. Synergy ACF228® has numerous

Quantity

N-acetylcysteine 100 mg L-methione 100 mg Di-indole-methane 83 mg L-carnosine 83 mg Deodorised garlic 50 mg Trans resveratrol 17 mg Vitamin B6 17 mg NDGA 3 mg Potassium iodide 3 mg Iodine 2.5 mg Methylfolate 800 mcg Chromium picolinate 120 mcg Selenium 100 mcg Vitamin B12 10 mcg Catalase 0.025 mg Dose ACF228® has been designed as a one capsule per day formula.

SPOTLIGHT

Visit us at: www.antiaging-systems.com BEC5® curaderm - a truly amazing skin cream The story of BEC5® cream is remarkable. When it is told people often can’t believe it- and when they realise the cream has been available for decades, they become flabbergasted! How so? Because this naturally derived skin cream has been shown to be virtually 100% effective in removing basal and squamous cell skin cancers (sic). History It all starts on the island of Vanuatu in the South Pacific, when a young man by the name of Bill Edward Cham (BEC) walked around the fields and noticed horses and cows rubbing themselves against a local plant called the Devil’s Apple, (a member of the eggplant family). Asking the farmers why they did this, he learnt that the

animals had skin lesions and the rubbing helped clear them up. As Dr. Cham was training to be a biochemist this fascinated him and over 20+ years his research revealed a remarkable secret.

Two excellent books on this subject are; the eggplant cancer cure and Curaderm a noninvasive medication for skin cancer.

Skin cancers He identified that the active ingredient was solasdines and that it ‘ate away’ a ribose coating on cancer cells that isn’t present on healthy cells. The result is that the cancer cells are exposed to the immune system as ‘non-self’ cells, then the natural process of apoptosis is induced and then the body rids itself of the cancer cells.

Application BEC5® cream is applied topically to SCC and BCC lesions twice a day and covered with a micropore. The typical treatment time is between 6 to 12 weeks. So why hasn’t this cream, (that avoids the need for surgery in most cases) not become famous and mainstream? The answer is simple, the active agent is natural and can’t be patented and therefore the current medical system will not promote it.

Documented history Many journals, particularly those in Australasia have published these studies and numerous magazines around the world have divulged this.

Note BEC5® is not suitable for melanoma cancers.

Can-C™ Eye-drops - a breakthrough for cataract

Can-C™ eye-drops are the original formula containing n-acetylcarnosine (NAC), a natural di-peptide that has potent anti-glycating and antioxidant properties to prevent lipid peroxidation. Clinicals Patients who placed 2-drops of Can-C™ into their eyes twice daily for a 5/6-month period reported:

►► An improvement in their visual acuity (90%) ►► An improvement in the clarity of their lens (88.9%)

Broad spectrum Evidence is mounting that Can-C™ is efficacious for many conditions including:

There have been numerous reports of cataract shrinkage and even disappearance with documented evidence that Can-C™ eye-drops remain effective (and safe) more than 24-months later.

►► Cataracts (particularly the senile version) for both humans and dogs ►► Glaucoma Presbyopia ►► Eye strain ►► Ocular inflammation ►► Blurred vision ►► Vitreous opacities and lesions ►► Diabetes mellitus complications ►► Contact lens comfort ►► Dry eye syndrome

Actuals The most commonly expressed initial reports are that glare is significantly improved, (for example night driving is easier) and color perception is enhanced. Most importantly, is an ability to read eye charts clearer, due to the better transmissivity of the lens.

Aging Matters | 39 |

SPOTLIGHT CentroPRO™ - improving mental recall speed ►► Accordingly, this reduction of membrane toxins like lipofuscin aids cellular communication. This is a key feature of the membrane hypothesis of aging- which has been published by Professor Nagy.

CentroPro™ capsules contain centrophenoxine, (pronounced, centrow-fen-ox-in) and it is a classic ‘nootropic.’

History ►► Centrophenoxine can increase acetylcholine levels in the brain. It is also very effective in reducing lipofuscin levels, this component is part of Alzheimer brain plaques.

►► Thus, centrophenoxine is useful for those concerned about Alzheimer’s, but in addition, centrophenoxine has been noted to help enhance and protect the performance of an healthy, aging individual. General cognitive benefits Classifying the precise benefits of the various nootropics can be tricky. Many people simply refer to their ailing cognitive facilities as “memory loss.”

further evaluation- in order to determine the precise nature of the problem. In such a case, centrophenoxine is perhaps best suited to the issue of recall speed. So, If your speech appears to be full of “ums” and “ers” (whilst your brain tries to catch up with your mouth), then it is likely that centrophenoxine will be an aid; helping to bring clarity and flow to speech and thought. Doses A typical dose for the ‘average’ person is 250 mg once or twice daily.

However, a quick breakdown of that statement requires

DepPRO™ - for focus and concentration DepPro™ contains deprenyl (also known as selegiline), it was created in the 1960s by Professor Joseph Knoll to treat Parkinson’s patients since deprenyl improves dopamine levels. Significant longevity studies Professor Knoll’s experiments with rats also produced the most incredible longevity benefits. When the animals were fed deprenyl in their food, they lived so much longer that even after the last nontreated rat died, the first of the deprenyl treated rats was yet to die! (Note: importantly, these results were verified independently in another study not undertaken by Professor Knoll). Based on this research, Dean, Fowkes and Morgenthaler, | 40 | Aging Matters

published in the book, Smart Drugs and Nutrients, that the loss of dopamine in aging humans can be mapped against both the development of Parkinson’s and even death. Mode of action For a long time deprenyl has been described as a MAO-b inhibitor, that it to say that is prevents this enzyme from destroying dopamine, leading to its improvement. Later, Professor Knoll noted that deprenyl also raises PEA levels and catecholamine sensitivity. Typical responses Deprenyl can assist:

►► The treatment of Parkinson’s and other dementias. ►► Male libido enhancement.

►► Boost metal energy levels especially focus and attention. ►► Life expectancy, at least in animals. Dosing Parkinson’s patients use high doses, but healthy aging adults typically use 1 mg to 3 mg per day, this is dependent on age and need. Note These doses do not consider synergy with other dopamine enhancing agents and, in such cases, would have to be adjusted accordingly.

SPOTLIGHT GHRPS - an alternative to growth hormone injections Dr. Daniel Rudman’s research in the late 1980s concluded that elderly patients using Growth Hormone (GH) could reverse their biological age-markers by as much as 20-years! Specifically, he noted that they had improved the patients’ skin, hair, muscle mass, decreased fat levels and enhanced levels of stamina, strength and well-being. The issue with GH, (other than its expense), is that it does have to be injected to be effective; this is because it is a 191-chain of aminoacids so it simply can’t be absorbed via any other route.

Furthermore, many countries have classified GH injections as a controlled substance, partly because of its anabolic actions. GHRPs Thankfully, Dr. Walker’s research has shown that the use of GHRPs, (growth hormone releasing peptides) have a much safer profile whilst enjoying many of the same benefits.

►► GHRPs can be sublingually and intranasally, and thus avoid the need for needles. ►► The GHRP feedback loop means that they cannot cause the pituitary to down-regulate production of GH. ►► GHRPs are not controlled substances.

GHRPs augment GH naturally into the blood. Synergy The main GHRP is GHRP2 which can be used sublingually, in addition there is also intranasal Sermorelin- this is the precursor to GH, (the first 29-aminoacids). Its function is to release existing stores of GH from the pituitary, rather than encourage more production. Dr. Walker suggests that combining sermorelin with GHRP2 can elicit up to a 5x greater quantity of GH into blood. Summary GHRPs have created a genuine alternative to GH injections; they are simpler and easier to use and at the same time they have a safer profile.

►► Rather than inducing a spike of GH in the blood,

MetPRO™ - improving the insulin sensitivity MetPro™ contains metformin, a diabetes type-2 treatment that has been used for many decades.

diabetic or otherwise not affected), have often noted that it helps them to maintain a healthy weight with lower fat levels etc.

Metformin differs from other insulin medications, since rather than increasing the production of insulin from the pancreas, it improves the sensitivity of the receptor site to insulin; in other words you ‘get more bang for your buck’ by improving the performance of insulin to peripheral tissues, (like muscles). This has interesting implications for aging since the neuroendocrine theory of aging teaches us that it is the loss of sensitivity at receptors that is a major ‘fault’ in aging.

Antiaging Dr. Ward Dean has stated that; “metformin is one of the most promising antiaging, lifeextending drugs available.” It’s a profound statement, but it is predicated on the amazing range of metformin’s clinical effects which include:

Weight loss Persons who utilise metformin, (even those who may be pre-

►► Enhancing the activity of anticancer drugs. ►► Suppressing the growth of some tumors. ►► Increasing the maximum life span of animals. Miles Metformin is a milestone, since it is the first medicine in the world to be granted an FDA approved study for antiaging titled; metformin in longevity study. Note Metformin does inhibit the uptake of vitamin B12, so in order to counter potential sideeffects it is recommended to supplement with B12 at the same time. Aging Matters | 41 |

SPOTLIGHT MZS™ - because not all melatonins’ are created equal

Melatonin is produced at night by the pineal gland to help regulate the circadian rhythm. As we age, the amount of melatonin we produce declines and it results in many persons having a lower quality of sleep. MZS™ has been formulated by the world’s foremost melatonin expert- Dr. Walter Pierpaoli, his MZS™ (melatonin, plus zinc and selenium), is totally unique since it is designed to mimic the natural night peak of melatoninleaving you refreshed and alert the following day. What does melatonin do? Melatonin is vital to protect our hormonal system, regulate immunity and repair our body’s cells. It is commonly used by shift workers and to treat jet-lag and age-related sleep disorders,

but its abilities go far beyond its sleep improvement properties. Antioxidant effects Melatonin is an extremely effective antioxidant; in fact, on a molecule to molecule basis, melatonin has proved to be more efficient in neutralizing toxic hydroxyl-radicals than the two well-known free radical scavengers, glutathione and mannitol.

►► Lowering the blood cholesterol, triglycerides and beta lipo-proteins. ►► Reducing the development of atherosclerosis. ►► Reducing insulin levels. ►► Increasing hypothalamopituitary sensitivity. ►► Improving the cellular immunity. ►► Enhancing the activity of anti-cancer drugs. ►► Suppressing the growth of some tumors. ►► Increasing the maximum life span of animals. ►► Melatonin and longevity

Melatonin’s effect on longevity is well documented. Laboratory tests on animals have demonstrated that melatonin increased their lifespans by 20%. MZS™ and ARMD Age related macular degeneration comes in two forms, wet and dry and it is a notoriously difficult disorder to treat- linked to blindness. In a 24-month study, (NY Academy of Science, 2005, 1057:384-392) on 100 patients showed that after 3 months, the majority of patients taking 3 mg of MZS™ nightly had halted the progression of their AMRD and at 6 months many reversed their ARMD. Remarkably this was true for both the wet and dry forms! Dr. Pierpaoli’s melatonin Dr. Pierpaoli’s MZS™ formula mimics the pineal gland’s release of melatonin when it is taken between 9-11 PM because it releases between 1-3 AM, the natural night-peak of melatonin in blood.

Nature’s Marvels™ - how peptide bioregulators in food are gene switches Professor Vladimir Khavinson is the President of the European Academy of Gerontology and Geriatrics. In the 1980’s he was a Colonel in the Soviet Union military medical corps. He and his team were approached by Kremlin who wanted a way to protect their troops from various problems. The research uncovered a remarkable link between short-chain peptides and DNA. Basically, short-chain peptidesin food act as gene specific switches; they termed them ‘peptide bioregulators.’ This former military secret is now available and to-date 21 have been identified to assist various organs, glands and tissues. | 42 | Aging Matters

These peptides, unlike proteins, can enter through the stomach and a comprehensive list of patents, confirms that each of the peptide bioregulators interact with DNA - activating repair and regenerative processes. Original materials from the trials Nature’s Marvels™ are the English packaged and approved peptide bioregulators from Professor Khavinson, (all bovine sourced). Here is the complete list: 1. Adrenal 2. Bladder 3. Blood vessels 4. Bone marrow 5. Brain (CNS) 6. Cartilage 7. Heart 8. Kidney 9. Liver 10. Lung 11. Muscle 12. Ovaries 13. Pancreas 14. Parathyroid

15. Pineal 17. Retina 19. Testes 21. Thyroid

16. Prostate 18. Stomach 20. Thymus

Dosing A typical program is as follows:

►► Start with an intensive course of 2-capsules once a day for 30-days. ►► Thereafter, use 2-capsules once a day for 10-days, repeat every 1, 2 or 3 months.

SPOTLIGHT Natural Estrogens and Progesterone for women - nHRT is the right kind of ‘HRT’ Esnatri™- a unique tri-estrogen Esnatri™ is a bioidentical triple estrogen cream. It comes directly from the work of Dr. Jonathan Wright who has highlighted that most women produce estrogens in the ratios of 90% estriol, 7% estrone and 3% estrone.

When estrogens were discovered in the 1920s they had to be derived from pregnant mare urine- all because a laboratory solution was too expensive to synthesize. But today everything has changed, yet this ancient practice continues! These facts have been pointed out by Jonathan Wright, M.D. in his book; ‘Don’t let your doctor give you horse urine!’

Usually, tri-estrogen preparations attempt to replicate the human hormones estriol, estradiol and estrone, in the ratio of 80:10:10. Some bi-estrogens entirely overlook estriol, claiming it is a ‘weak’ estrogen. However, women naturally produce high levels of estriol since it is considered to have anticarcinogenic effects. Horse estrogens are, as you would expect, not identical to human. Yet some physicians still prescribe them, even though bioidentical estrogens can now be easily produced. Some people

believe that the known sideeffects from ‘HRT’ are because the correct natural human hormones are not utilised. In other words, women should be using ‘nHRT.’ ProgestPro™ ProgestPro™ is a 5% bioidentical progesterone cream and it is a counterbalance to estrogens. For whilst women can significantly decline in estrogen levels during menopause, they rarely reach zero production levels, whereas progesterone can sometimes not be measured at all. It is also the low level of progesterone that significantly impacts bone strength, leading onto osteoporosis. So, there are numerous reasons to ensure that progesterone is taken alongside estrogen in an nHRT program.

OxyPRO™ - for passion and sex OxyPro™ contains oxytocin, a hormone produced by the hypothalamus but excreted via the pituitary gland. Its orthodox role is to help women give birth, since the large dose that’s injected helps relax the uterus and alleviates the passage of the child. Meanwhile, Dr. Thierry Hertoghe’s book; ‘passion, sex and longevity, the oxytocin adventure’- has shown it to have many other roles. The love hormone Oxytocin has been dubbed ‘the love hormone’. This is because oxytocin can induce feelings of bonding and care. Not just between individuals, but even with animals too! Oxytocin measurements have been taken between lovers, friends, relatives, parents and their children

etc. From those results, it has been noted that oxytocin levels are higher when they are in their presence. Mothers naturally bond with their children, but even men, (especially those who experience the live birth), express their emotions as wanting to care and protect their offspring, these effects may be attributable to the release of oxytocin, hence triggering the bond. On the other side of the coin, psychopaths are notoriously low in their oxytocin levels, which may be a cause of their uncaring feelings towards other humans. The pain and orgasm connection Fibromyalgia can be a very debilitating disorder with a lot of pain, sometimes constant for those who suffer with it. In

women with fibromyalgia it was noted that when they were experiencing an orgasm, they felt no pain at all. Later, it transpired that women undergo a burst of oxytocin during orgasm. Trials were undertaken to see if oxytocin supplementation could alleviate the pain of fibromyalgia, there was some success, but the side effect noted was that those women now enjoyed multiple orgasms! This was a fact picked up on by the popular press and is probably singularly the action most responsible for bringing oxytocin into the public gaze. Aging Matters | 43 |

SPOTLIGHT PiraPRO™ - the original nootropic UCB in the 1960s. Originally, it was used for travel and altitude sickness, but shortly afterward people realised that piracetam had positive effects on cognition.

Nootropic is a term meaning ‘towards the mind’ and they were originally designed for senile dementias, but now they have become popular for aging individuals to enhance their mental and cognitive processes. Ward Dean, M.D. has highlighted these facts in his ‘Smart Drug’ series of books; ever since then the term ‘smart drugs’ has become mainstream. Piracetam, the original PiraPro™ contains piracetam and piracetam was the first nootropic developed by Dr. Giurgea at

What does piracetam do? Piracetam is used for a wide range of conditions. For example, it has been shown to improve attention levels and memory retention. Piracetam can slow down ‘senile involution.’ In other trials, piracetam has improved memory consolidation in those suffering from ‘age-related memory impairment.’ Piracetam has aided patients recovering from strokes, inparticular improving post stroke speech impairment (aphasia). Another use has been for acute and chronic cerebral ischaemia, (decreased blood flow to the brain). Piracetam has even

increased neuronal activity in the brain when measured with EEG. For normal individuals, piracetam can enhance idea creation and the ability to ‘see things through.’ In other words, to have ideas and then be able to bring them to fruition. The level of clarity piracetam induces is often described as; “the fog has lifted.” How does piracetam work? Piracetam’s key method of action is upon the Corpus Callosum, the region of the brain that links the two hemispheres. Many experts believe this enables piracetam users to channel greater brain potential by connecting the logical side of the brain with the creative side. This could be described as a Yin and Yang effect.

Thyroids - supporting the hypothyroid epidemic result in poor concentration, confusion, memory problems, cold hands and feet and weight gain.

Dr. Broda Barnes estimated that 40% of adults are deficient in thyroid hormones. As the thyroid gland is of pivotal importance, a lack of its function can affect a wide variety of age-related health disorders. Ergo, supplementation can have many positive effects. The thyroid gland The thyroid controls the body's metabolism, (the rate at which it burns calories for energy) and the body's utilization of fat; so a decline in thyroid function, can | 44 | Aging Matters

Other conditions triggered by an underactive thyroid are painful musculoskeletal issues that affect tendons, muscles and ligaments. Do I need a thyroid supplement? A doctor can check your blood levels, but a simple method is to take your body temperature when you wake in the morning. It should be in the range of 97.8 to 98.2 degrees Fahrenheit. If it is regularly lower than 97.8 F you could be hypothyroid and if regularly higher than 98.2 F then hyperthyroid.

Synthetic vs. natural thyroids Synthetic thyroids typically only contain T3 or T4, but natural thyroids (like Armour® etc.) are of porcine origin and contain the full spectrum of T1, T2, T3 and T4 thyroid hormones. Converting between the two The table provides a helpful guide to the conversion rates for those wishing to switch from synthetic thyroids to natural versions. As always, we recommend consulting with a physician before making changes to your health program.

SPOTLIGHT Youth Gems® - the peptide bioregulators for skin Youth Gems® contain four synthetic peptide bioregulators that have been combined into topical skin preparations so that their unique gene-switching performance can be bought to the field of aesthetic medicine. What peptides? This beauty product line contains the following four peptides: Thymus peptide It stimulates tissue regeneration and the synthesis of proteins. It has an anti-inflammatory action, improves the healing time of wounds, plus antioxidant, immune stimulating, & antistress actions. Pineal peptide It regulates metabolic processes and increases protein synthesis in skin cells, helping to normalize the lipid peroxidation processes.

Cartilage peptide It stimulates regeneration of fibroblasts and keratinocytes, and it also strengthens collagen structure of elastic skin fibres and increases elasticity. Blood vessel peptide This regulates metabolic processes in the vascular wall, normalizes vascular tone and restores skin microcirculation. What else is in Youth Gems®? In addition to the 4 peptides, Youth Gems® also contain many other beneficial natural agentsincluding: Neovitin® (a ginseng complex), olive oil, raisin-seed oil, Argon oil, Soya oil, Jojoba oil, Bisabolol (a chamomile extract), Peony extract, sodium hyaluronate (hyaluronan), green-tea extract, cocoa oil, carrageenan, winter bloom, almond extract & vitamin E.

Real world results Improved metabolism in vascular wall cells, new growth of skin cells, enhanced antioxidant activity, increased blood flow circulation and greater moisturization has led to smoother skin, with fewer wrinkles and more elasticity. This helps to lift the face contours producing a more radiant and youthful appearance. All of these beneficial effects were noted in 100% of women who used Youth Gems® in the voluntary clinical trial conducted in St. Petersburg. Available in anti-wrinkle serum, face cream and body milk.

Publications for antiaging, preventative and regenerative health enthusiasts www.thelongevity.store

Aging Matters | 45 |

SPOTLIGHT

Can-C eye-drops Note: US$ prices are subject to shipping and handling (and additional taxes where appropriate). Disclaimer: All educational information is provided under the IAS terms and conditions (which may change without notice) and does not replace the advice of your physician. Restrictions may apply in some countries. (*plus S&H).

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The benefits of vitamin B17 B17Pro® 40x 100mg tablets

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Formula each tablet contains: Amygdalin.................................................102.05mg Zinc Oxide....................................................12.5mg Pancreatic Enzymes......................................300mg Consisting of Protease.......... 32.700mg UPS Units, Amylase................................. 35.100mg UPS Units, Lipase....................................... 7.800mg UPS Units

* 90% * *

*% Daily Value not established Note: US$ prices are subject to shipping and handling (and additional taxes where appropriate). Disclaimer: All educational information is provided under the IAS terms and conditions (which may change without notice) and does not replace the advice of your physician. Restrictions may apply in some countries.

www.antiaging-systems.com

| 46 | Aging Matters

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SPOTLIGHT We introduce the latest dental care range that contains peptides for mouth health. Its unique peptide formula guards against gingivitis, halitosis, and receding gums, all whilst strengthening teeth enamel. The mouthwash is a concentrate, so only 1 ml. needs be placed into water and gargled and then spat out. The repair gel need only be used once a week. It is placed into a provided gum shield and worn for 15-minutes. Afterward the teeth may be brushed and cleaned with water as normal.

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Aging Matters | 47 |

Media Page Welcome to the media page; here you will find links to videos and podcasts that we hope are of interest to you. Many of them are located on You Tube under the Antiaging Systems channel. Please subscribe to stay up to date with new uploads as they occur. These videos and audio files are specific to age-related disorders and occasionally actual medical conditions, they highlight the latest thinking and approaches, many of them from leading professionals in the field.

www.antiaging-systems. com/videos/

Often, they are interviews, occasionally they are PowerPoint presentations and sometimes they are even professionally made clips. We even have recordings from lectures given at conferences. We hope you like the selection we have made out for you here.

The ivermectin global summit. Listen to physicians from all around the world, including countries such as Australia, Bolivia, Canada, Mexico, Peru, and the UK describe their clinical experiences with using ivermectin in the treatment of Covid-19.

www.antiaging-systems.com/videos/ivermectin-global-summit

Leading experts discuss the use of BEC5® Curaderm skin cream in the treatment of skin caners. See and hear for yourself the discovery of a natural skin cream that is reversing both squamous cell and basal cell carcinomas.

www.antiaging-systems.com/videos/leading-experts-discuss-the-benefits-ofbec5-curaderm-cream | 48 | Aging Matters

Introducing the peptide bioregulator revolution. Discover the history about the discovery of short chain peptides found in food that act as gene switches.

www.antiaging-systems.com/videos/introducing-the-peptide-revolution

Dr. Thierry Hertoghe discusses the uses of oxytocin. Belgium’s leading hormone expert describes how oxytocin improves relations, heightens orgasms, and helps to improve empathy.

www.antiaging-systems.com/videos/dr-thierry-hertoghe-talks-about-oxytocin

Telomeres, telomerase activation and TA65® A professional clip that shows the importance of telomeres in health and aging.

www.antiaging-systems.com/videos/ta65-telomeres-telomerase-activation Aging Matters | 49 |

Antiaging Systems www.antiaging-systems.com is your comprehensive resource for

information about all the leading commercially available antiaging, preventative, and regenerative products available today.

Visit www.antiaging-systems.com

and find articles, videos, audio-files, all referenced with a guide of where to obtain your needs. Currently the site covers topics related to all the following products:

BOOKS ►► Atlas of Endocrinology V2 by Thierry Hertoghe, MD ►► Eyesight Saviors by Marios Kyriazis, MD ►► Natural Skin Cancer Treatments by Bill Cham, PhD ►► Passion, Sex & Oxytocin by Thierry Hertoghe, MD

►► Patient Hormone Handbook by Thierry Hertoghe, MD ►► Peptide Bioregulator Revolution by Dr. Kyriazis ►► Peptides in the Control of Ageing by Prof. Khavinson

►► Physician Hormone Handbook V2 by Thierry Hertoghe, MD ►► Reversing Physical Aging V1 by Thierry Hertoghe, MD ►► Testosterone Therapy for Real Gentlemen by Thierry Hertoghe, MD

DIAGNOSTICS ►► Bio-Clip™ CUFF

►► Foodsafe®

GHRPs (growth hormone releasing peptides) ►► GHRP2 (GHRP2Pro™)

►► Sermorelin (SermPro™)

HORMONES ►► ►► ►► ►► ►► ►►

Aldosterone (AldoPro™) Desmopressin (Minurin®) DHEA (DHEAPro™) Estrogens (Esnatri™) HCG (HCGPro™) Hydrocortisone (HydrocortPro™)

►► ►► ►► ►► ►► ►►

Melatonin (MelaMaxPro™) Melatonin (MZS™) MSH2 (MSH2Pro™) Oxytocin (OxyPro™) Pregnenolone (PregPro™) Progesterone (ProgestPro™)

►► Thyroids (natural, T3) ►► TRH (Abaris™) ►► Vasopressin (VasoPro™)

NUTRITION ►► ►► ►► ►► ►► ►► ►►

1st Line™ (OSCN) ACF228® BloodSugarPro™ Boluoke® (lumbrokinase) BoostPro™ Can-C™ Plus DIMPro™

| 50 | Aging Matters

►► ►► ►► ►► ►► ►► ►►

EnergyPro™ LacticPro™ LongevityPro NADPro™ (NMN) NitricPro™ PainPro™ StressPro™

►► ►► ►► ►► ►►

Symprove® TA65® TestoXLR8Pro™™ VigorPro™ ViralPro™

PEPTIDE BIOREGULATORS (bovine source, includes Nature’s Marvels™) ►► ►► ►► ►►

Adrenal (Glandokort®) Bladder (Chitomur®) Blood Vessels (Ventfort®) Bone Marrow (Bonomarlot®) ►► Cartilage (Sigumir®) ►► CNS/ Brain (Cerluten®) ►► Heart (Chelohart®)

►► ►► ►► ►► ►► ►► ►► ►►

Kidney (Pielotax®) Liver (Svetinorm®) Lungs (Taxorest®) Muscle (Gotratix®) Ovaries (Zhenoluten®) Pancreas (Suprefort®) Parathyroid (Bonothyrk®) Pineal (Endoluten®)

►► ►► ►► ►► ►► ►►

Prostate (Libidon®) Retina (Visoluten®) Stomach (Stamakort®) Testes (Testoluten®) Thymus (Vladonix®) Thyroid (Thyreogen®)

PEPTIDE BIOREGULATORS (synthetic source) ►► Blood Vessels (Vesugen®) ►► Cartilage (Сartalax®)

►► CNS/ Brain (Pinealon®) ►► Liver (Ovagen®)

►► Lungs (Chonluten®) ►► Thymus (Crystagen®)

►► Deprenyl (DepPro™) ►► Hydergine® (HyPro™) ►► Modafinil (ModaPro™)

►► Picamilone (PicPro™) ►► Piracetam (PiraPro™)

►► EDTA (EDTAPro™) ►► GH3Pro™ (Gerovital-H3®) ►► Ivermectin (IvermectinPro™) ►► Metformin (MetPro™)

►► ►► ►► ►►

►► OraltidePro™ peptide rinse ►► OraltidePro™ peptide tooth gel

►► RetinPro™ (0.05% tretinoin) ►► Youth Gems® (peptide creams)

SMARTS ►► Adrafinil (AdraPro™) ►► Centrophenoxine (CentroPro™)

SPECIALIST ►► 4MU (4MUPro™) ►► Aminoguanidine (AminoPro™) ►► B17Pro™ (amadaylin) ►► Dasatinib (DasaPro™) ►► DMSA (DMSAPro™)

Naltrexone (NalPro™) Rapamycin (RapaPro™) Sildenafil (SildenafilPro™) Tadalafil (TadalafilPro™)

TOPICALS ►► BEC5® Curaderm cream ►► Can-C™ eye-drops ►► JointPro™ cream (peptide)

For more information visit:

www.antiaging-systems.com The World’s most comprehensive antiaging resource

Aging Matters | 51 |

• The World’s most comprehensive antiaging resource • Global perspective • More than 30 years' experience www.antiaging-systems.com

Aging Matters Magazine V3 Issue 38 2021, STRESS IS GOOD!

Articles inside

The science of aging interventions Professor Rattan explains hormesis

Dr. Marios Kyriazis documents what is useful

Forefront Recent stories in the news

Welcome To the second edition of 2021

Introducing our recommended videos

Testimonials Professionals’ comment on IAS