REVERSING BIOLOGICAL AGING WITH PEPTIDE BIOREGULATORS

An interview with Dr. Bill Lawrence

by Phil Micans.

PM: Bill, I'm so excited to chat with you again and learn how the participants have performed in your studies.

BL: Thanks, Phil. I am happy to provide an update.

PM: Before we get into that, I recommend that people read our original interview, (outlined above) but would you mind doing a quick recap? In other words, what made you do this study in the first place?

BL: As I mentioned in the previous interview, my primary motivation was selfpreservation. Unfortunately, all the males in my family experience premature death, commonly in their fifties and early sixties, including my father at age sixty-four. I am now seventy-six. I was thirtyseven when my father died and based on family history, I had already lived more than half my probable lifespan. At that time, I was a tax and estate planning attorney and an entrepreneur building medical buildings, shopping centers, etc. Around that time, a wealthy eighty-year- old estate planning client in poor health told me he would give up his entire wealth if he could have just ten more years of healthy life. That was one of those life-changing moments as I realized my priorities needed to change. So, I sold everything, returned to graduate school, and became a biogerontology researcher. Somewhere along the way, I had an epiphany. Most of us, especially those north of sixty, feel time has accelerated or, as people often say, “it’s flying by." We start our week on Monday, and suddenly it is Friday, or it's February, and next thing we know, we're carving the Thanksgiving turkey. The epiphany was I could not slow time down, but it may be possible to add more time. I can add a decade, even much more, to my life by reversing biological age. At the end of this interview, I will mention the ‘Bridge’ strategy, which, as a scientist, I believe will allow me to add another thirty or more years to my life.

Russian clinical studies with peptide bioregulators

Ed.- Three years ago, I had the pleasure to interview Dr. Bill Lawrence in a piece entitled 'forever young.' It appeared in issue 33 (1) of the 2019 Aging Matters™ magazine. At that time, Dr. Lawrence had begun the 3-year journey to apply peptide bioregulators (PB) to 39-patients. Today, it's 3-years later, so we get to find out what happened! Note: PM is me, and BL is Dr. Lawrence.

BL: My first exposure to Peptide Bioregulators came in 2013 when I discovered a published longevity study by Professor Vladimir Khavinson, Director of the St. Petersburg Institute of Bioregulation and Gerontology. The study was summarized in our interview that was published in the 2019 Aging Matters™ magazine. The twelve-year study reported a dramatic reduction in all-cause mortality in an elderly control group using Dr. Khavinson's peptides, principally the pineal gland and thymus. However, it was extraordinary that the significant mortality reduction was achieved using only two peptides, which were only used during the first three years! I later understood the peptides accomplished this by cellular rejuvenation or reprogramming.

PM: At that time, the three principal PBs in use were the pineal, the thymus, and the blood vessels. Did you just use them, or others too?

BL: Today, there are twentyone natural food-based peptides, otherwise known as Cytomaxes®. We use all of these in our studies. The expanded number of peptides will produce even more significant longevity and health span benefits than the original trials. Subsequently, I met with Professor Khavinson, became affiliated with the St. Petersburg Institute, and we agreed to an American study to confirm the peptides were an effective cellular rejuvenation intervention. While there are many claims for products and substances for cellular rejuvenation. I am unaware of any intervention other than Peptide Bioregulators, with human clinical study proof of cellular regeneration. One exception might be stem cell therapy, especially VSEL [Ed.Very Small Embryonic Like Stem Cells]. The rejuvenation or regeneration of human stem and other cells results in tissue, organ, and system regeneration, i.e., endocrine, central nervous, respiratory, lymphatic, etc. When organ/ system regeneration occurs, the result is enhanced longevity and health span, and a true biological age reversal.

PM: Those Soviet studies were truly remarkable; their size and time-period is unheard of in the west.

Peptide clinical study overview

BL: Indeed and of course human longevity or longitudinal studies require decades to complete. Our studies use the reversal of biological age biomarkers as a proxy for longevity intervention. Biological age is an estimator that predicts a person's health and present life expectancy. On the other hand, chronological age is simply the time that elapses since birth. Aging in humans is a complex and multi-stage process. Therefore, it is impossible to compress biological age into a single test or number. While there are many ways to estimate biological age, most biogerontologists would agree that improvement in telomere and DNA methylation (DNA/m) biomarkers represent two of the more accurate biological age markers available now. Evidence of biological age reversal would be the modification of biological age markers. Telomerase activation results in telomere restoration, allowing increased cellular replication. Cell replication is a primary determinant supporting extended lifespan. Numerous published studies confirm that longer telomeres are associated with longevity and enhanced health.

Modification of age-related methylation measured by the Horvath Epigenetic Clock is believed to be a primary longevity and organ regeneration intervention.

PM: Just a reminder for folks to get more background information by reading our V3 issue 33 (1), 2019 article in Aging Matters™ available online at: www.aging-matters. com to download. Also, more specific information is available from several interviews with Dr. Lawrence on YouTube by searching ‘Bill Lawrence Peptides.’ But let’s just take a step back for a moment to ask:

What are peptides?

BL: These peptide bioregulators are shortchain amino acids derived from food. Specifically, these peptides are chains of 2 to 4 amino acids sourced from food molecules derived from young calves with small molecular weights. As a result, they activate stem cell function and penetrate cell membranes and nuclear membranes for epigenetic regulation of gene expression and activation of the telomerase enzyme. Russian and European clinical peptide studies prove that these peptides can significantly increase human longevity and reduce allcause mortality. The result is enhanced life and health span, defined as the number of years without significant age-related disease and organ degeneration. Professor Khavinson has been quoted: "Peptide Bioregulators regenerate organs impaired by aging, disease, and trauma. The peptides developed at the St. Petersburg Institute of Bioregulation and Gerontology constitute a proven biological reprogramming technology, rejuvenating cells to revitalize tissue/ organs and entire bodies, ultimately decreasing vulnerability to age-related degeneration and prolonging human life." The peptides were initially developed on behalf of and used by the Soviet Union Military, Cosmonaut space program, and their Olympic athletes.

The studies was, do longer telomeres extend and enhance longevity and health span? Several thousand published studies have now confirmed the answer is yes. There is a consensus among gerontology scientists, supported by numerous studies, that one of the most critical aging causes in humans is the progressive shortening of telomeres, especially in human stem cells, because of cell replication. Humans age because their stem cells age. Peptides activate an enzyme, Telomerase, which maintains and lengthen telomeres in stem cells. This results in better stem cell function/ cellular rejuvenation and slower organ and organism aging. Numerous clinical studies confirm people with longer telomeres experience extended and healthier lives. For additional telomere background information, I recommend the ‘Telomerase Revolution’ book by Dr. Michael Fossel.

Telomere age

been lengthened after a peptide protocol, equivalent to a fifty-year-old. This becomes their reduced telomere age. Success is adding telomeres to the end of the chromosome via peptide-induced telomerase activation, allowing more cell replication, and reported as a reduction in telomeres age.

PM: And how have your patients performed in this regard?

BL: At the end of three years, over sixty TAP participants had an average telomere age reversal (lengthening) equivalent to approximately twenty-two years. On average, participants experience a telomere lengthening of about seven years for each year in the study.

PM: Wow! Are there any goals/ aims?

Epigenetic Methylation Study (EMS)

BL: We commenced two separate peptide studies. The goal of both studies is to determine if and to what extent peptides can reverse and improve two essential biomarkers of biological aging, telomeres, and DNA/m. The telomere study, Telomerase Activation Protocol (TAP), started in 2017. Prior published studies had proven these peptides could lengthen telomeres. The remaining question

PM: So, when it comes to biological age, how is it reversed by lengthening telomeres?

BL: Well, if a person's baseline telomere measurement reports telomeres equivalent to a seventy-year-old, this is their baseline telomere ‘age,’ which will be older or younger than their chronological age. If older, we refer to this as accelerated telomere aging. Let’s assume that their telomeres have

BL: For a participant over sixty, the telomere goal is to reset their telomeres equivalent to a 30- to 40-year-old. This was proof the peptides could reverse this biomarker of biological aging. The telomere study is now entering its fifth year. Today, there are over one hundred participants, either active or after achieving their telomere goals, on a minimal maintenance program. At seventy-six, my telomere length range is between those of a 35- to 45-year-old.

PM: And why was it necessary/ important to also study DNA methylation?

BL: The second peptide study commenced in early 2020 to determine if peptides can reverse Epigenetic Age (DNA/m). Methylation is one of the essential chemical processes that our bodies use to ensure our genes work correctly. Some scientists describe methylation as the ‘Windows operating system for the body.’ As we age, especially in older humans, or those with unhealthy lifestyles, diet, toxic environments, chronic stress, etc., there are changes to our DNA caused by methylation. Some refer to this as ‘methylation rust’ or agerelated ‘toxic’ methylation. Eventually, human aging and the epigenetic influences result in methylation found at specific DNA sites, turning off certain protective genes and turning on genes that promote aging. The body is a complex organism with various ‘gears and switches’ that must function correctly to operate optimally. Think of methylation as the mechanism that allows the gears to turn and biological switches to be turned on and off for a host of systems in the body. Unfortunately, as humans age, methylation levels increase (chemical methyl tags) and cause the gears and switches (DNA) to malfunction. Different lifestyle and behavioral factors such as diet, sleep, exercise, smoking, and drinking alcohol can also affect the composition and location of the chemical groups that bind to our

DNA. Environmental factors such as stress, trauma, or even neighborhoods or zip codes may also impact. Early life adversity, chronic stress, childhood health, personality, intelligence, and less measurable but vital puzzle pieces such as social connectedness, isolation, and a sense of purpose throughout our lives affect methylation. Early adversities accelerate epigenetic aging long after they occur, in proportion to the total number of such experience.

Dr. Steven Horvath, a professor and biostatistician scientist at UCLA, discovered hundreds of age-related DNA sites (CpG Islands) where methylation changes could be observed, affecting DNA and age-related genes. Additional research revealed that a DNA biological age (EpiAge®) could be calculated based on methylation status.

Dr. Horvath created the ‘Horvath Epigenetic Clock’ to measure epigenetic methylation status and report an Epigenetic age compared to chronological age. The Horvath Clock is considered one of the current most accurate assessments of biological age as a potential predictor of future mortality.

Epigenetic age reporting

BL: : Several commercial labs can analyze methylation and determine an epigenetic biological age from that information. This is reported as Epigenetic Age/ EpiAge® or, as one lab prefers, TruAge®. Like telomere reporting, comparing baseline EpiAge® and post peptide protocol EpiAge® is evidence that peptides can modify and reverse this aspect of biological aging. These testing technologies confirm peptides are effective cellular rejuvenation interventions. Our EMS clinical study goes beyond a resetting of EpiAge®. It also determines a participant's all-cause mortality risk. Dr. Horvath's research discovered if a person has an EpiAge® ‘age’ eight or more years greater than their chronological age, their all-cause mortality risk is 100% greater than their same-age peers, (figure 1). Conversely, if a person's EpiAge® age is seven years less than their chronological age, their risk of death is reduced by 50% compared to their peers, (figure 2). Dr. Horvath acknowledges that the ‘Horvath Clock’ accurately measures biological versus chronological age. His frustration is not being aware of any effective intervention to modify the ‘toxic’ or age-promoting methylation. Preliminary two-year results for the EMS clinical study suggest Peptide Bioregulators can reduce agerelated ‘toxic’ methylation levels resulting in a reversal of the Horvath Clock and a significant reduction of all-cause mortality. The EMS study goal is to use the peptides to reduce all-cause mortality risk as measured by the Horvath Epigenetic Clock.

The tentative results are very positive with our first eightythree participants.

PM: What are you typically finding with your study participants?

BL: On average, a new EMS participant will often be 2 to 4 years ‘older’ than their chronological age. According to Dr. Horvath's research, this represents a 25% to 50% increase in all-cause mortality risk. After two years on a peptide protocol, the average participant reduced their EpiAge® by about five years. That may not seem significant compared to decades of telomere age reduction but quantifying the two biomarkers is not comparable. A positive outcome with telomere peptide interventions (lengthened telomeres) is reported as a ‘telomere age’ versus chronological age. This is based on telomere length (base pair) measurement. As telomeres lengthen from the average seventy-year-old to those found in a forty-yearold, it reflects a reduction in telomere biological age. Epigenetic age is reported similarly but is far more complex than telomere assessment as it involves the entire body (systems and organs), methylation, and gene analysis. First, an epigenetic baseline ‘age’ is assessed and compared to chronological age. Post peptide intervention after testing then reports a reduced epigenetic biological age. Both types of biological age reporting are helpful but primarily serve to confirm progress in reducing biological age markers. Therefore, both these age biomarkers reported a biological age as a number. However, Dr. Horvath discovered that epigenetic age is also linked to mortality risk. Therefore, this EpiAge® is essential to assess all-cause mortality risk rather than simply evaluating biological age. In the EMS study, we focus primarily on the difference between EpiAge® and chronological age because it relates to mortality risk. We refer to this as the ‘gap.’ Unlike telomere age assessment (telomere versus chronological age), success is determined by increasing the positive gap between present chronological age and EpiAge®.

PM: What is important about this gap?

BL: Well, if a new participant has an EpiAge® two years older than their chronological age, they have an increased risk of all-cause mortality of 25% compared to their same-age peers. We refer to this higher risk as a two-year negative gap. Conversely, if the participant's EpiAge® is two years less than their chronological age, this is referred to as a two-year positive gap. The initial goal is to reduce their EpiAge® to their chronological age. This reverses an increased mortality risk to neutral (same risk as their peers) or a neutral gap. The next stage is to create a positive gap. If the peptide protocol reduces their EpiAge® an additional four years less than their chronological age, we define this as a four-year positive gap. At four years less than chronological age, the all-cause mortality risk is now about 30% less than the participant's peers. Our goal is to achieve a sevenyear positive gap. Then their all-cause mortality risk is

50% less than their peers. On a personal note, my most recent EpiAge® test reports show that I have a positive gap of ten years. This represents a potential all-cause mortality risk that’s 70% less than my peers of the same chronological age.

PM: Impressive, how do these results compare with other antiaging methodologies?

BL: I am unaware of any other medical or health intervention, technology, pharmaceutical, nutraceutical, or substance, confirmed with scientific evidence that can reduce all-cause mortality by even a small percentage.

Clinical study procedure

PM: So, what is the typical procedure for a patient?

BL: We perform baseline telomere and EpiAge® testing with each study participant. The results reveal their telomere and EpiAge® compared to their chronological age. Based on that data and any health issues they want to address; we design a peptide protocol unique to each person. This generally is 5-7 different peptides per month (thymus, pineal, heart, brain, kidney, etc.) Then, over a year, we rotate through all the twenty-one peptides. The dosage is two capsules per day for ten days each month and then off the specific peptide for twenty days. This cycling or pulsing avoids organ reliance on the peptides. Instead, the goal is cellular rejuvenation, tissue enhancement, and organ regeneration such that the specific organ is restored and functioning independently. The peptide program is typically three to four years and then onto maintenance if desired. This is vastly different than conventional Western medicine, where a patient is likely to remain on medication for their entire life.

PM: And what were some of the initial reactions? i.e., were there any kind of differences noted?

BL: Yes, there were significant improvements in their telomeres with lengthened telomeres and in their Epigenetic Age- with a reduction in all-cause mortality risk biomarkers. In addition, both studies report improved energy, sleep, skin, and cognitive and physical function. While not intended for medical treatment, participants' blood tests highlighted significant improvements in various organ functionality markers, such as the kidney and liver, etc.

Clinical study results

PM: Very nice, and on average how well do most people perform?

BL: Over 90% of the telomere participants reach their telomere goal in 2 to 3 years. Furthermore, the average participant over three years reduces their telomere age by twenty-two ‘years.’ We are just now reaching the twoyear mark in the Epigenetic study. Interim results reflect a high percentage of participants who have reversed their EpiAge® on average by approximately five years. This typically shifts them from the increased risk to the decreased mortality risk group. We believe that in another couple of years, these participants will have reached their optimal goal of seven years less than chronological age and achieved a mortality risk of fifty percent less than their peers.

PM: How many persons are in these studies today?

BL: Over one hundred and twenty people, primarily physicians and other health providers, are now participating in the two studies. There are ninety active participants in the testing and full peptide protocol. The remaining have met their goals, and everyone in this group has chosen to stay on a minimal maintenance peptide program. Three people have left the studies due to geographic moves to other countries. Four people have left the program due to financial stress caused by Covid government mandates.

Adverse effects

PM: Were there any side effects or other issues?

BL: The peptides are sourced from young calves and are classified as food supplements; they have been used in Russia for over forty years on hundreds of thousands of people with no adverse effects.

PM: And as your trial continued- I might add all during the tough time of CV19 lockdowns- did anything else appear or change?

BL: Yes, participants exposed to the spike protein from the Covid virus and the ‘vaccines’ are experiencing accelerated

The bridge

PM: What do you see as the next big step to extreme longevity?

BL: I’d like to take a moment to explain my longevity strategy for living well beyond one hundred years. I call this the Bridge. It is based on employing antiaging therapeutics now available and those soon available as the bridge between now and the immediate future. The idea is that one must

There are dozens of wellfunded biotech companies attempting cellular reprogramming to treat age-associated diseases and potentially rejuvenate tissues and organs. Billions have been spent and invested using the following and developing interventions using Quantum Computers, artificial intelligence. CRISPR (genome sequencing), gene sequencing and therapy, stem cells and exosomes, replacement organs by 3D printing, robotics, nanotechnology, microrobots, etc. Most of these will be available in the next decade. The key is to stay as healthy as possible and remain on the forefront of longevity interventions to take advantage of these technologies as they become available. Peptide Bioregulators are the only intervention presently available I am aware of that causes cellular rejuvenation or reprogramming. Therefore, Peptide Bioregulators are essential and the key for crossing the longevity bridge. cellular aging. This is caused by impairment of the cellular DNA Repair Mechanism. About 8% of the participants in the two studies reported Covid virus infection and/ or vaccine injections. All of them have experienced accelerated aging caused by the spike proteins. We are addressing this situation with a DNA Repair Mechanism protocol consisting of peptides, nutraceuticals, and spike protein interventions. create the highest degree of physical, mental, and emotional health possible today. Then maintain that level over the next ten years (crossing the bridge). Sometime in the next decade, when one arrives at the other side of the bridge, the most common causes of death and disability will have been resolved. Heart disease, diabetes, dementia, cancer, etc., will have cures or become chronic, manageable conditions.

PM: And finally, in a short statement, what would you say has been accomplished in this 3-year PB trial?

BL: We've reversed these patients' biological age, reprogrammed, or regenerated their organs and systems via cellular rejuvenation, and significantly reduced their all-cause mortality risk.

PM: This is quite remarkable, and yet currently, it's hardly known even in the longevity field. Hopefully, that will change very soon, and we will certainly want to revisit this subject. Thank you, Bill, for your time, efforts, and dedication to making this happen.

BL: My pleasure Phil.

Metformin, which had been available in Europe since the 1950s, was not approved for sale in the U.S. until the late 1990s.

DR. WARD DEAN ANSWERS YOUR QUESTIONS:

DEAR DR. DEAN,

I have read a lot in your articles about metformin, and it seems to me to be very universal, having benefits for diabetes, weight loss, immunity, PCOS/ fertility and even cancer.

May I ask, why are its effects so broad? Is there a related factor between all these disorders?

I do appreciate all your knowledge.

Mrs. R.M., England inhibition of mitochondrial complex I in the electron transport chain (ETC) which resulted in the reduction of endogenous production of Reactive Oxygen Species (ROS—i.e., free radicals), and action as an activator of adenosine monophosphate kinase (AMPK) which results in the production of adenosine triphosphate (ATP), the universal energy molecule. inhibits mTOR, modulates oxidative stress, and removes senescent cells. These processes, together, (3, bottom) affect inflammation, cellular survival, stress defence, autophagy, and protein synthesis, which are all major biological outcomes associated with aging/ longevity.

► Dear Mrs., R.M.

Yes, there is a related factor that is shared by all the disorders you cited - it’s called the aging process.

I first learned about Metformin in 1981, when I read a book by a Russian physician/ scientist named Vladimir Dilman. 1 Dilman explained that Metformin was an antidiabetic drug that had several unique properties. He explained his belief that Metformin’s metabolic effects were due to a single mechanism—that of inhibiting fatty acid oxidation.

As a world-renowned expert in anti-aging and longevity science, Dr. Dean is recognised for his pioneering work with nutritional and pharmacological approaches to delay aging and ameliorate age related diseases. Dr. Dean served as a member of the Gerontological Society of America, the American Geriatrics Society, the Association of Military Surgeons of the U.S., the American Physiological Society, and an Associate Fellow, Aerospace Medical Association and was also the first vice president of A4M.

He believed that diabetes resulted from impaired glucose tolerance, insulin resistance with secondary hyperinsulinemia, and enhanced gluconeogenesis by the liver - and he demonstrated that Metformin was able to reverse all these metabolic changes. He performed studies which showed that Metformin treatment increased the sensitivity of insulin receptors and that it also restored receptor sensitivity to all the body’s hormones - including those in the hypothalamus. In essence, Metformin seemed to be a “whole-body metabolic rejuvenator.”

Dilman was an anti-aging pioneer, who stated that “Metformin was the drug of choice for prevention of premature development of diseases of aging.” At that time, Dilman was a “voice in the wilderness”, as the only antidiabetic biguanide that had been available in the U.S. was phenformin, but it had been taken off the market in 1978 due to excess deaths caused by lactic acidosis. And hypercholesterolemia, and atherosclerosis, and reduce the incidence of many cancers and other diseases of aging, the mechanisms causing these effects were not clearly identified, and they are still under investigation.

Several of Metformin’s “anti-aging mechanisms” were determined to be the

In 2012, Dr. Nir Barzilai, of the Albert Einstein College of Medicine in New York, clarified and enhanced metformin’s mechanisms, as illustrated in Fig. 1, 2, 3 As can be seen in the schematic, outside the cell (1, top) Metformin affects the receptor for cytokines, insulin, IGF-1, and adiponectin, all of which are activated with aging, and when modulated, are associated with longevity. Within the cell (2, middle) Metformin inhibits the inflammatory pathway, activates AMPK,

In 2013, an international research team proposed nine cellular and molecular Hallmarks of Aging that are generally considered to contribute to the aging process. namely: (1) Genomic Instability; (2) Epigenetic Alterations; (3) Loss of Proteostsis; (4) Deregulated Nutrient Sensing; (5) Mitochondrial Dysfunction; (6) Cellular Senescence; (7) Stem Cell Exhaustion; (8) Altered Intercellular Communication; and (9) Telomere Attrition. The impact this article had on the gerontological research community can be seen by the overwhelming response of scientists in the field by their proliferation of favorable citations, the number of which has increased every year since the article was published (Fig. 2). 4

2018-527; 2019-622; 2020812; 2021-980; 2022-381 (so far)—Total-4245).

Even Dr. Barzilai and his colleagues responded favorably to the Hallmarks article, by proposing how Metformin attenuates the Hallmarks of Aging to varying degrees. They demonstrated how Metformin directly targets four of the hallmarks (inner circle—Genomic Instability, Deregulated Nutrient Sensing, Loss of Proteostasis, and Altered Intracellular Communication) via its action on AMPK, SIRT1, mTORC1, IIS pathways, protection against macromolecular damage,

References: improved autophagy response, and reduced inflammation. The hallmarks in the outer circle (stem cell exhaustion, cellular senescence, mitochondrial dysfunction, epigenetic alteration, and telomere attrition) are secondary targets, due to their attenuation being mediated by Metformin’s role on a primary target. 5

Professor Dilman’s contributions to anti-aging medicine are profound. In addition to being an early proponent of the life-extending benefits of Metformin, members of his team such as Vladimir Anisimov and Vladimir Khavinson continue his research with Metformin and the anti-aging polypeptides of which Dilman was an early proponent and investigator.

I hope this somewhat technical answer responds to your question,

Respectfully, Ward Dean, MD

1. Dilman V. The Law of Deviation of Homeostasis and the Diseases of Aging, 1981, John Wright PSG, Inc. Boston.

2. Barzilai N, Huffman DM, Muzumdar RH, and Bartke A. The Critical Role of Metabolic Pathways in Aging. Diabetes 61 1315-1322, 2012.

3. Barzilai N, Crandall JP, Kritchevsky SB, and Espeland MA. Metformin as a Tool to Target Aging. Cell Metabolism 23, 1060-1065.

4. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, and Kroemer G (2013). The Hallmarks of Aging. Cell 153(6): 1194-1217. [PubMed: 23746838].

5. Kukarni AS, Gubbi S, Barzilai N. Benefits of Metformin in Attenuating the Hallmarks of Aging. Cell Metab. 2020, July 07, doi.10.1016/j. cmet,2020.04.001.

DEAR DR. DEAN, I would like to tell you about my issue and that I have been using liquid deprenyl on and off now, (more on than off) for 8 years at a dose of 2 or 3 mg daily. As a 78-yearold man I notice and like its effects. I feel more focused and mentally energised and have an arousal to my libido. Recently, I have developed a prostate issue of frequent urination, (particularly at night) and a slightly enlarged prostate- which naturally I do not want to get worse.

Please feel free to guide me on this and tell me if deprenyl is contraindicated.

With the greatest of respect.

Mr. H.M., Spain.

If you’ve read my articles about Deprenyl in previous issues of Aging Matters™, you’re well-aware of its antiaging, cognitive-enhancing effects. (1, 2) Deprenyl has few, if any, adverse effects, and I strongly doubt that it is adversely affecting your prostate.

It sounds like you have benign prostatic hyperplasia (BPH), which occurs in a high percentage of men as they get older. The standard medical treatment is to use 5-alpha reductase inhibitors like finasteride (Proscar®), which block the conversion of testosterone to dihydrotestosterone (DHT); alpha-receptor blockers like tamsulosin (Flo-Max®); and/or phosphodiesterase inhibitors (PDE-Is) like sildenafil (Viagra®). Some men respond better to one of the medications than palmetto extract (Seronoa repens, 320 mg/day); Pygeum Africanum (100-200 mg/day) (4); Stinging nettles (1200 mg/ day) (5); and Beta sistosterol (60-195 mg/day). (6)

I hope those suggestions will do you as much good as the Deprenyl did.

Ward Dean, MD

others; often a combination works best.

A recent meta-analysis reviewed seven studies that compared regimens of combinations of tamsulosin and various PDE-Is. The authors concluded that for men with lower urinary tract symptoms (LUTS) due to BPH, the optimum regimen was daily tamsulosin (0.4 mg/day) plus sildenafil 25-50 mg 4 days per week. (3)

In addition to standard medical therapy (or instead of, as chosen by many men), there are likewise several over-the-counter substances that help to shrink the prostate and relieve urinary symptoms. These include saw

References:

1. Dean, W. Deprenyl and Alzheimer’s Disease update. Aging Matters, No. 3, 2016, 24-27

2. Dean W, Deprenyl--an aphrodisiac & life extension agent. Aging Matters, Vol 3 No. 1, 2019, 11-17.

3. Ma C, Zhang J, Cai Z, Xiong H, and Li H. Defining the efficacy and safety of Phosphodiesterase Type 5 Inhibitors with Tamsulosin for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia with or without erectile dysfunction. BioMed Research International, 2020, Article ID 1419520, 8 pages.

4. Stamatiou K, Magri V, Samara E, Perletti G. Serenoa repens and Pygeum Africanum in the treatment of BPH. Hellenic Urology, Vol 31, Issue 3, 2019, 33-40.

5. Ghorbanibirgani A, Khalili A, Zamani L. The efficacy of stinging nettle (Urtica dioica) in patients with Benign Prostatic Hyperplasia: A randomized double-blind study in 100 patients. Iranian Red Crescent Medical Journal, Vol 13, No. 1, 2013, 9-10.

6. Wilt TJ, Ishani A, MacDonald R, Stark G, Mulrow CD, Lau J. Beta sitosterols for benign prostatic hyperplasia (Review). Cochrane Database of Systematic Reviews, 2011, 1-20.

DEAR DR. DEAN,

I am about to start on a regular program of piracetam at 800 mg three times a day. After reading your books and online pieces I thought this was a good place to start. My goal is to improve my awareness and creativity. My financial job is quite demanding, and I notice that I am not as ‘mentally bright’ as I was 10-years ago, (I am now 46) and I would like to stay ‘on top of my game’. So, can I ask you, is my dosage good and should I be considering anything else that is safe and effective in combination?

In gratitude.

Mr. W.V., Switzerland idea - and may enable you to benefit from lower doses of each.

For example, Hydergine® (HyPro™) is a cerebral vasodilator, which improves blood flow to the brain, and with long-term use increases the growth of dendrites (neural connections) in the brain.

Modafinil (ModaPro™) and/or Adrafinil

► Dear W.V.,

2,400 mg of Piracetam is a good starting dose to evaluate your tolerance (although adverse effects are very rare), but I usually recommend a higher dose. Most of the clinical studies of Piracetam used 4,800 mg—and many used even higher doses, ranging up to 12 gm (12,000 mg) per day!

Combining Piracetam with other cognitive enhancers that act by different mechanisms is a good

(AdraPro™) increase receptor sensitivity of a variety of cerebral neurotransmitters, and act as increasers of wakefulness and alertness. This class of medications is approved for those who suffer from “shift work sleep disorder,” but helps “wake up the brains” of the rest of us, without causing the adverse effects of stimulants like amphetamines.

For those who do not suffer from Parkinson’s or Alzheimer’s Disease, low doses (1-2 mg/day) of Selegeline (Deprenyl/ DepPro™) reduce the levels of

Monoamine Oxidase B which tend to rise with age, enhancing cognitive performance, increasing libido, alleviating depression (and generally improving mood), and may increase the likelihood of living longer!

Centrophenoxine (Lucidril®, CentroPro™) acts as a mild cerebral stimulant and cell membrane stabilizer, that was developed by Prof. Imre Zs.-Nagy as a cognitiveenhancing anti-aging drug. The recommended dosage is 500 mg once or twice/day.

Over-the-counter supplements which may enhance cognitive performance include

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Buy 3+ $25.00 each phosphatidylserine 300 mg/ day, Acetyl-L-Carnitine 500 mg three times/day, and Ginkgo biloba.

Please let us know of your results,

Respectfully, Ward Dean, MD

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