Omega-3 Fatty Acids and Aging

By: Kasey Hutchinson, RDN

The following arti cle is not endorsed and/or supported by The American Academy of Anti -Aging Medicine. The purposes of this publicati on do not imply endorsement and/or support of any author, company or theme related to this arti cle.

Dietary patterns among humans have continued to transform throughout history, but genetic and nutritional needs remain constant. Researchers estimate that during Paleolithic times, people consumed a balanced 1:1 ratio of omega-3 to omega-6 fatty acids. 1 However, in modern, westernized cultures, people consume nearly 20 times more omega-6’s than omega3’s. Not surprisingly, this imbalance is associated with a rise in various age-related and in ammatory diseases. 1,3 However, key dietary interventions may be able to intercept premature aging and related conditions. Research shows that increasing the consumption of omega-3’s may improve human longevity and quality of life in older adults.

OMEGA - 3’S IN A NUTSHELL

Omega-3 fatty acids include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and others. ALA is mainly plant-derived and can be found in foods such as chia, hemp, and  ax seed. EPA, DHA, and DPA, on the other hand, are predominantly found in the fatty tissues of  sh, such as lake trout, sardines, and salmon. Contrarily, the main sources of omega-6 fatty acids in the diet come predominantly from processed foods and animals products, whose consumption is increasing throughout the world and leading to an imbalance of omega-3:omega-6 fatty acid intake. 3

ALA must be converted to EPA, DHA, or others, in order for it to complete its functional role in the human body. 4  is process is extremely ine cient in humans with conversion rates of about 15%. 4 Excess ALA is typically stored or used for energy, like other dietary fats.  us, the need for marine sources of omega3’s in the human diet is apparent.  is can be accomplished either through increased consumption of seafood or  sh oil supplementation. 4

A recently published, 25-year prospective cohort study found an inverse relationship between serum levels of omega-3 fatty acids and incidence of age-related diseases. 5 More speci cally, researchers measured blood levels of DPA, DHA, and EPA

concentrations in this cohort of 2,622 people. Individuals withthe highest omega-3 serum content (6% of total fatty acids) had an 18% decreased risk of unhealthy aging and cognitive decline, and improved quality of life compared to people with lower omega-3 serum concentrations. Based on these results, researchers state that increasing dietary requirements of marine-based omega-3 fatty acids in older adults is highly recommended.

AA:EPA RATIOS AND AGE

In order to get a more complete sense of the in ammatory tone of the body, it is important to evaluate serum levels of EPA, DHA, and DPA against serum levels of the omega-6 fatty acid arachidonic acid (AA). In fact, the AA:EPA ratio is quickly growing in popularity for its use as a biomarker in age-related diseases, such as cancer, heart disease, chronic kidney disease, and more. Indeed, the connection between in ammation and the progression of aging has been cited so frequently throughout scienti c literature that researchers eventually coined the term ‘in ammaging’ to describe this relationship. 6

While in ammation has a useful purpose in the body, such as pathogen elimination, it must be brought to a close in a process known as in ammation resolution.  is process is mediated by omega-3 derivatives called pro-resolving mediators (PRMs), which help regenerate damaged tissue. 7 Insu cient stores of EPA, DHA, and DPA in the tissue can prevent PRM biosynthesis. In fact, low concentrations of PRMs have been found in patients with age-related diseases such as chronic kidney disease, Alzheimer’s disease, and atherosclerosis. Since the tissue status of PRMs and serum status of AA:EPA are largely a ected by dietary intake, nutrition interventions hold a promising solution to combat in ammaging. 7-9

FISH OIL, SERUM FATTY ACIDS, AND QUALITY OF LIFE IN ELDERLY ADULTS

Fish oil supplementation is a proven approach for reducing AA:EPA ratios.  is concurrently improves quality of life and reduces risk of disease among elderly adults. A recent double-blind, placebo-controlled study assessed the impact of omega-3 supplementation on symptoms of depression in a group of elderly, depressed women. 8 Results indicated that 2.5 g/day of omega-3 fatty acids, at a ratio of 2:1 EPA to DHA, signi cantly improved depressive symptoms in as little as 8 weeks.  ere was also a signi cant reduction in AA:EPA ratios in depressed patients following treatment with  sh oil. AA:EPA ratios were reduced from 37 to a ratio of 22 – just above the average healthy adult ratio of 15-20. 8

Similar studies suggest that reducing AA:EPA ratios protects against coronary artery disease (CAD) and cancer proliferation among older individuals. 9,10 While the e ects of omega-3 fatty acids on brain and heart health are welldocumented, researchers are beginning to uncover more ways in which these essential fatty acids promote healthy aging.

OMEGA - 3, GUT HEALTH AND HUMAN LONGEVITY

 e gut associated lymphoid tissue (GALT) is the largest immune organ in the human body. 11 Gut microbes play a vital role in GALT formation and maintenance.  e gut microbiome also protects the body against pathogens and is involved in disease prevention. 11 However, as humans enter their later stages of life, signi cant changes occur to the gut microbial composition. Namely, there is a substantial decrease in bene cial bacteria such as Bacteroidetes, Prevotella, Lactobacillus, Streptococcus, and Faecalibacterium prausnitzii and an increase in levels of Ruminococcus and Enterobacterium. 12  is microbial trend correlates with an increase in both infectious and non-infectious disease, frailty, and in ammatory conditions.

Numerous studies suggest that increasing omega-3 (DHA and EPA) intake, either through diet or supplementation, can ameliorate age-related gut dysbiosis. 13-15 In fact,  sh oil supplementation has been shown to increase the abundance of Clostridiaceae, Akkermansiaceae, and Bi dobacterium, while reducing the abundance of pathogenic gut microbes. 15 Furthermore, it appears that such interventions increase shortchain fatty acid (SCFA) production and decrease systemic in ammation associated with metabolic endotoxemia. 15

Short-chain fatty acids are crucial metabolites generated by the gut microbiome for strengthening immunity and combating in ammation. Yet, production of these bene cial molecules is sharply reduced in advanced age. Consequently,

lower levels of intestinal SCFA in elderly adults is associated with aging-related maladies such as constipation, appetite disturbances, frailty, weight loss, cognitive decline, high blood pressure, vitamin D de ciency, diabetes, arthritis, sarcopenia, and more. 16 Boosting SCFA levels in the gut o ers a signi cant contribution towards graceful aging. However, this isn’t the only omega-3-related mechanism tied to longevity. It appears that marine-based fatty acids are directly related to telomere length.

TELOMERES AND OMEGA - 3 FATTY ACIDS

Telomeres are structures at the end of each strand of DNA that protect chromosomes. With each cellular replication cycle, telomeres shorten, triggering senescence (aging) and apoptosis (cell death), which may be enhanced by stress and in ammation. 17 As telomeres shorten, physical signs of aging appear and the risk of age-related diseases, such as cancer, Parkinson’s disease, osteoporosis, osteoarthritis, and coronary artery disease, increases.  e rate of shortening is a ected by genetics, diet, environment, in ammation, and lifestyle. Telomere length is thus a fundamental indicator of biological age, which means that reducing telomere shortening is central to human longevity research.

A prospective cohort study of 608 patients with coronary artery disease investigated serum omega-3 fatty acid levels in relation to telomere length. 18 Fasting blood samples were taken from volunteers at a baseline examination and in a 5-year follow up visit. Average telomere length was measured from the DNA from blood samples. Results indicated that higher baseline omega-3 blood levels were associated with an increase in telomere length, regardless of other lifestyle factors. In fact, for each standard deviation increase in baseline omega-3 levels, there was a 32% decrease in telomere shortening. 18

Similarly, in a double-blind, randomized trial, researchers assessed changes in telomere length in relation to omega-3 supplementation. 19  is 4-month study involved 106 healthy, overweight individuals who were randomly divided into three groups.  e high dose group (2.5 g/ day omega-3), low dose group (1.25 g/day omega-3) and a placebo group, who received corn oil supplements. At the end of the study the low dose group showed an increase in telomere length of 21 base pairs (bps), while the high dose group showed a 51 bps increase.  e control group experienced a 43 bps decrease in telomere length. While these di erences were not considered signi cant, researchers came to a fascinating conclusion. Omega-3 supplementation changed fatty acid ratios, speci cally the omega-6:omega-3 ratios in the serum. For every unit decrease in n-6:n-3 PUFA ratio, there was a 20 bps increase in telomere length (p = 0.02), indicating that metabolism and intestinal absorption may a ect how well these fats become incorporated into body tissues. 19  is research, along with others, point to an important connection between in ammation, oxidative stress, and immune cell aging.

OMEGA - 3’S ENHANCE LONGEVITY AND PROMOTE GRACEFUL AGING: BIOCHEMICAL MECHANISMS

In vivo and animal models help to elucidate the speci c mechanisms by which omega-3 fatty acids a ect telomere length. Researchers discovered that marine-based fatty acids a ect aging due to their e ect on the redox-telomereantioncogene axis. 20 In a recent study, published in the journal Oncotarget, D-galactose was administered to mice in order to produce advanced glycation end-products (AGEs) in vivo.  is protocol is favored among researchers because it mimics the aging process and represents a well-known free radical theory of aging. Mice were then divided into groups to receive either  sh oil, polyunsaturated fats, or corn oil. Blood samples were taken to assess the e ects of various dietary fats on telomere length, telomerase activity, superoxidase activity, cerebral monoamine oxidase, redox activity, and activation of the antioncogene, a gene which suppresses tumor growth.

Similar to the concept of “in ammaging”, the free radical theory implies that organisms age due to oxidation of tissue and accumulation of free radicals.  is is accompanied by the loss of telomere length and the increase in physical signs of aging. 20 Free radicals, such as superoxide, also impair the activity of telomerase, the enzyme involved in telomere lengthening. Superoxidase activity is typically diminished in people of advanced age and the resulting surge in free radicals damages telomeres, causing senescence and cellular aging. Results from this study indicate that  sh oil supplementation

improves redox state, increases hepatic and cardiac superoxide dismutase (SOD) activity, reduces cerebral monoamine oxidase activity, and leads to increased length of telomeres as compared to the corn oil group. Furthermore, DHA signi cantly improved activation of testicular antioncogene, which suggests that it can protect against testicular cancer. Fish oil may therefore improve longevity and reduce the risk of age-related cognitive decline and disease through these biochemical mechanisms.

CONCLUSION

 e connection between diet and longevity has long been recognized. Scientists have observed that seafood intake is correlated with a long, happy life, yet only in recent years has this been validated with experimental studies. 21 Cold water  sh are a rich source of bioavailable omega-3 fatty acids, such as EPA, DHA, and DPA. As these molecules are absorbed into the body and incorporated into blood cells and tissues, they begin to elicit a powerful, preventative impact on aging and age-related diseases. Similarly, supplementation with omega3’s and SPMs that are extracted and puri ed from marine sources can provide signi cant health bene ts by improving the quality of life in older adults and boosting longevity. In conclusion, the consumption of wild-caught, cold water  sh and the supplementation of high quality  sh oil from reputable sources can go a long way toward improving health outcomes and human longevity.

REFERENCES

Scaioli E, et al. The Imbalance between n-6/n-3 Polyunsaturated Fatty Acids and Inflammatory Bowel Disease: A Comprehensive Review and Future Therapeutic Perspectives. Int J Mol Sci. 2017;18(12):2619. Lawrenson JG, et al. Omega 3 fatty acids for preventing or slowing the progression of age-related macular degeneration. Cochrane Database of Systematic Reviews. 2012. Table 3. Food sources of linoleic acid (PFA 18:2), listed in descending order by percentages of their contribution to intake, based on data from the National Health and Nutrition Examination Survey 2005-2006. Food sources of linoleic acid (PFA 18:2), listed in descending order by percentages of their contribution to intake, based on data from the National Health and Nutrition Examination Survey 2005-2006. https:// epi.grants.cancer.gov/diet/foodsources/fatty_acids/table3.html. Accessed February 6, 2020. Office of Dietary Supplements - Omega-3 Fatty Acids. NIH Office of Dietary Supplements. https://ods.od.nih.gov/factsheets/ Omega3FattyAcids-HealthProfessional/. Accessed February 6, 2020. Lai H. Serial circulating omega 3 polyunsaturated fatty acids and healthy ageing among older adults in the Cardiovascular Health Study: prospective cohort study. Bmj. 2018;363:k4067. Franceschi C, Campisi J. Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2014;69(Suppl 1). doi:10.1093/gerona/glu057. Doyle, R., et al. Pro-resolving lipid mediators: Agents of antiageing? Seminars in Immunology. 2018; 40: 36-48. doi:10.1016/j. smim.2018.09.002 Rizzo AM, Corsetto PA, Montorfano G, et al. Comparison between the AA/EPA ratio in depressed and non depressed elderly females: omega-3 fatty acid supplementation correlates with improved symptoms but does not change immunological parameters. Nutr J. 2012;11:82. Published 2012 Oct 10. Serikawa, et al. The ratio of eicosapentaenoic acid to arachidonic acid is a critical risk factor for acute coronary syndrome in middle-aged older patients as well as younger adult patients. 2014; 63(1): 35-40. 10.

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Sulforofan Extra

Mitochondrial Rescue Ph: (561) 767-0721 www.mitochondrialrescue.com

This product is plant-based supplement that contains glucoraphanin from the broccoli seed extract. In nature, when broccoli seed/sprout cells break open(when damaged or eaten) glucoraphanin is released and mixes with a naturally occurring companion enzyme(myrosinase). When these two compounds meet, they form a new substance called sulforaphane. Most of the other broccoli supplements available in the market only contain glucoraphanin and rely on the ability of the gut flora to convert to sulforaphane. Our unique supplement includes the enzyme myrosinase in the capsule, so the conversion to sulforaphane is much more efficient, rapidly absorbed, transported systemically to the blood, metabolized, conjugated and excreted in the urine. Sulforaphane activates the body’s natural detoxification and antioxidant enzymes and protects the cells from free radical damage for days after being consumed. It is packed into gastrointestinal resistant capsules, with slow release, allowing content release in the upper intestine. Dosing: 1 capsule per day (200mg). 60 capsules per package

Turiva

Ortho Molecular Products Ph: (800) 332-2351 www.orthomolecularproducts.com

Turiva is a powerful turmeric supplement that contains an exclusive blend of bioactive phytonutrients that make up the Complete Turmeric Matrix for increased clinical efficacy. The Complete Turmeric Matrix is unique to Ortho Molecular Products and delivers the full-spectrum immune health benefits of the whole turmeric root. The formula contains standardized amounts of curcumin, turmerin protein and turmeric essential oils, and helps maintain normal inflammatory balance, supports a healthy microbiome and balances immune function.

DUTCHtest Cycle Mapping Plus

Precision Analytical Inc. Ph: (503) 687-2050 www.dutchtest.com

Cycle Mapping Plus is the newest panel from DUTCH, combining DUTCH’s Cycle Mapping and DUTCH Plus panels to provide a full assessment of a woman’s cycle and answer important questions for patients with monthlong symptoms, infertility, and PCOS. This test is a comprehensive assessment, mapping the progesterone and estrogen pattern throughout the menstrual cycle as well providing an assessment of sex hormone metabolites, cortisol metabolites, organic acids, melatonin (6-OHMS), and 8-OHdG. Cycle Mapping Plus also adds the Cortisol Awakening Response (CAR) to bring another important piece of the HPA-axis into focus.

Potassium Idodide

Protocol For Life Balance Ph: (877) 776-8610 www.protocolforlife.com

Protocol For Life Balance ® is introducing non-GMO Potassium Iodide, a clean form of iodine for your patients in need of thyroid cleansing.* With 23 mg iodine and 7 mg potassium per tablet, this highly bioavailable Potassium Iodide can displace thyroid-bound iodine, thus allowing for the rapid renal elimination of undesirable forms of iodine and bromide stored in the body.* It’s ideally used for a short period of time.

NAD+ Gold™

Quicksilver Scientific Ph: (303) 531-0861 www.quicksilverscientific.com

NAD+ Gold™ is a next-generation age management elixir containing liposomal nicotinamide mononucleotide (NMN) and trimethylglycine (TMG). NMN is a stable precursor to NAD+, the body’s premier cellular energy and anti-aging molecule, which is further supported by the methyl donor TMG for balanced activity. Liposomal delivery significantly improves upon cellular delivery of NMN as it mimics the body’s own transport system, offering the most effective and fast-acting formulation of this molecule available.

TA-65 Rx | 250 Unit Tablets

T.A. Sciences Ph: (212) 588-8805 www.tasciences.com

T.A. Sciences introduces a new size to their TA-65 Nutritional Supplement Pro-Series collection. TA-65 is now available in a 250 Unit Tablet. The Pro Series is available exclusively to physicians.

Ultra Pure® Fish Oil 1000

Vital Nutrients Ph: (888) 328-9992 www.vitalnutrients.net

Our new Ultra Pure® Fish Oil 1000, Triglyceride is pharmaceutical-grade and produced from sustainably caught anchovies, sardines and mackerel. These softgel capsules have a natural lemon flavor and help maintain general health, provide inflammatory balance and joint and cartilage support.*

Inception MD Profactor Revitalizing Serum

Vitelle Labs Ph: (877) 902-2332 Toll Free www.vitellelab.com

Experience the outstanding rejuvenating properties of Hyaluronic Acid and Growth Factors in one versatile serum. Profactor Rejuvenating Serum contains BIO-Placenta, a combination of five synthesized growth factors (EGF, IGF-1, Acidic FGF, Basic FGF, VEGF), Vitamin B9, and Acetylated Glutamine. This advanced formula supports healthy aging by fortifying and promoting resilience within the cellular matrix. Passionfruit and Lemon Fruit Acids encourage exfoliation, gently improving overall radiance, texture and appearance.

Broad Spectrum CBNplus - Orange 1000mg

Your CBD Store Ph: (727) 235-0720 www.sunflora.org

SunMed™ CBNplus is a CBD nighttime tincture formulated with an extract that is rich in minor cannabinoid Cannabinol (CBN). This tincture contains just as much CBN as our Neuro does with CBG, making up about 5% of its profile. However, unlike our water solubles, its oil base allows for the delivery of this brilliant blend of extracts and essential oils in a sustained manner—guiding you into a soothing, deep sleep that will leave you refreshed and rejuvenated as you rise and prepare for the new day. *This product is not intended to cure or treat insomnia.

Memory and Methylation Profile

ZRT Laboratory Ph: (866) 600-1636 www.zrtlab.com

Methylation & Memory – Basic Profile | Tests included: Estradiol, Progesterone, Testosterone, TSH, Folate, Vitamin B12, Homocysteine, Brain-derived Neurotrophic Factor (BDNF) | The Methylation and Memory Basic Profile gives an overview of the hormones and nutrients that, if deficient, can accelerate cardiovascular disease as well as memory loss, increasing risk for senile dementia and Alzheimer’s disease. This profile also includes BDNF, which is important for health of the central and peripheral nervous systems, and low levels are associated with higher risk for Alzheimer’s disease. | Methylation & Memory – Advanced Profile | Tests included: Estradiol, Progesterone | The Methylation and Memory Advanced profile consists of the same analytes as the Basic Profile but additionally gives a broader overview of the adrenal and thyroid hormones and nutrients that, if deficient (e.g., DHEA-S, fT3, fT4, FER) or excessive (C, SHBG, TPOab), can accelerate cardiovascular disease and memory loss, increasing risk for cardiovascular events as well as senile dementia and Alzheimer’s disease.