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Best Anti-Aging and Longevity Supplements

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Enhance your vitality and well-being with the top scientifically-backed dietary supplements for slowing down the aging process and promoting longevity.

What Contributes to Longevity?

The biggest factors that contribute to longevity are diet, lifestyle, genetic, social, and environmental factors.1

Obesity, poor blood sugar control, smoking, and alcohol abuse contribute greatly to earlier death. In many cases, these factors are the underlying contributors to the two major causes of death, namely heart disease and cancer.

What Causes Aging?

There are many theories on what causes aging, however, there are essentially two types. 

Programmed Theory vs. Damage Theory

Programmed theories believe there is some sort of a genetic clock ticking away which determines when old age sets in, while damage theories believe aging is a result of cumulative damage to cells and genetic materials. Human aging is likely the result of both a genetic clock and cellular damage.

One of the most popular program theories of aging is the telomere shortening theory. Telomeres are the end-cap segments of DNA (our genetic material). Each time a cell replicates, a small piece of DNA is taken off the telomere and gets shorter. The shorter the telomere gets, the more it affects gene expression. The result of the change in gene expression is susceptibility to cellular aging.

The most popular damage theory is the free radical theory of aging. This theory contends that damage caused by free radicals contributes to aging and age-associated disease. Free radicals are highly reactive molecules that can bind to and destroy cellular compounds. Free radicals may be derived from our environment (sunlight, X-rays, radiation, chemicals), ingested foods or drinks, or produced within our bodies during chemical reactions. Antioxidants are compounds that block free radicals or oxidative damage.

Glycosylation Theory

Another theory to highlight is the glycosylation theory. This theory involves blood sugar molecules attaching to cellular proteins, leading to protein dysfunction. Excessive glycosylation forms advanced glycation end-products (AGEs), causing enzyme inactivation, damage to proteins, weakened immune function, and increased autoimmune disease risk. AGEs, like free radicals, are linked to chronic illnesses. High-sugar diets and diabetes promote glycosylation, contributing to telomere shortening.

One popular measure of blood sugar control and the degree of glycosylation in the body is the blood measurement of A1C, which measures the percentage of glycosylated hemoglobin in red blood cells. If you have poor blood sugar control or an elevated A1C, the most important way to fight aging and promote longevity is to follow diet and supplementation strategies to improve blood sugar control. The plant compound berberine has shown considerable benefits in supporting blood sugar control in human double-blind, clinical trials and may be an important anti-aging and longevity supplement for those dealing with excessive glycosylation.2,3 

What Speeds Up Aging?

Accelerated aging is characterized by several factors including chronic, low-grade, inflammation, reduced mitochondrial function, excessive glycosylation, and other signs of cellular damage. All of these factors are interrelated. 

Typically, as people age there is an increase in inflammation and a decline in mitochondrial numbers and function. This combination results in the accumulation of cellular debris. With sufficient energy, cells can clear this cellular waste through autophagy. But with decreased mitochondrial function and energy production the cellular debris is not cleared through autophagy and as a result, is another big trigger of chronic inflammation.

Is Memory Loss  Inevitable With Aging?

Absolutely not. Since the brain is the most metabolically active tissue in the body, the effects of aging can hit it hard. But steps can be taken to not only stop memory loss and mental decline but also to reverse it to a degree. Young or old, our nutritional status plays a vital role in determining how well our brain functions. It is also important to point out that there is a very strong link between cardiovascular health and brain health. Not surprisingly, many of the same dietary, lifestyle, and supplement strategies to support heart health have the additional benefit (either directly or indirectly) in supporting brain health.

Top Anti-Aging And Longevity Supplements

My general recommendation as far as supplements go is to make sure that your nutritional foundation is strong. In addition to a health-promoting diet, I believe the following key supplements are important as foundational approaches to anti-aging and longevity:

  1. Multivitamin: A high-potency multiple vitamin and mineral formula to provide a nutritional “insurance policy” that all essential micronutrients are provided in sufficient amounts. 
  2. Vitamin D: Extra vitamin D3 because deficiency is very common (at least 50% of the general population). Higher vitamin D3 levels are associated with a 5-year difference in telomere length.6 What this means is that a 70-year-old woman with higher vitamin D3 levels would have a biological age of 65 years. Take a daily dosage of 2,000 to 5,000 IU of D3.
  3. Omega-3: A pharmaceutical-grade, high-quality fish oil supplement sufficient to provide a combined total of 1,000 to 2,000 mg of EPA+DHA daily. 
  4. Turmeric: A plant-based antioxidant. For anti-aging and longevity benefits, consider taking curcumin, the active compound found in turmeric (Curcuma longa). Curcumin exerts a multitude of effects that fight aging and promote longevity, but it is its profound effects on inflammation that make it so important. These beneficial effects have been observed in clinical studies showing certain curcumin preparations (most notably Theracurmin®, Meriva®, and C3 Complex®) to produce positive effects in protecting against brain aging, promoting joint health, and improving metabolism.7 

To build upon this foundation, I would recommend focusing on supplements that work to support glutathione, enhance mitochondrial function, exert a positive effect on autophagy, and reduce silent inflammation.

What Supplements Support Glutathione?

One of the most important compounds that every cell in your body produces is glutathione. The cells use this valuable compound to protect themselves from damage as well as aid in detoxifying harmful compounds. 

Glutathione is a small protein molecule composed of the amino acids glutamate, cysteine, and glycine. Over 100 years of research, more than 100,000 scientific papers have established maintaining cellular glutathione levels as one of the most important keys in maintaining proper cellular function, immune health, and slowing the aging process.8 

The most popular supplemental approaches to boost glutathione levels are taking either glutathione (GSH) or N-acetylcysteine (NAC).8,9 The typical dosage for oral supplementation of reduced GSH is 250 to 1,000 mg daily. For NAC the dosage is generally 500 to 1,000 mg daily. 

Another anti-aging molecule that behaves in similar ways to glutathione is ergothioneine (ERGO), a unique naturally occurring amino acid found in all foods but by far the richest dietary source is mushrooms. ERGO exerts several biological actions that protect and enhance cellular function including acting as an antioxidant, inflammation regulator, and detoxification aid. There is emerging evidence that diets rich in ERGO exert these protective effects and promote longevity. For these reasons, ERGO has been referred to as the “longevity vitamin.”10,11

Evidence shows that ERGO may protect against oxidative damage, inflammation, and decreased mitochondrial function linked to cognitive decline in the elderly.12,13 ERGO levels were significantly lower in frail elderly subjects compared to non-frail elderly subjects.14 And another study showed that higher ERGO levels were associated with the preservation of gait (manner of walking).15 Disturbance in gait is a common sign of aging.

ERGO has been shown to decrease oxidative stress in virtually every tissue and cell type studied. This represents a systemic anti-aging effect.12  

Since mushrooms are by far the primary dietary source, if a person is not regularly eating mushrooms, they are likely deficient in ERGO and can benefit from taking an ERGO supplement.

What Supplements Enhance Mitochondrial Function?

Mitochondria are the energy-producing compartments in our cells. Decreased mitochondrial function is a big factor in aging, decreased cognitive function, and poor memory. Enhancing mitochondrial function requires four primary considerations:

  • Providing all essential nutrients 
  • Utilizing mitochondrial enhancers
  • Improving insulin sensitivity and blood sugar control
  • Enhancing detoxification processes
  • Reducing exposure to damaging factors (e.g., toxins)

In regard to utilizing mitochondrial enhancers, a good place to start is the combination of coenzyme Q10 (CoQ10) and pyrroloquinoline quinone (PQQ). This combination produces better results compared with taking them separately. CoQ10 is very well known, but PQQ is just beginning to get popular. PQQ is a powerful antioxidant that specifically protects against mitochondrial damage as well as exerts other important actions critical to mitochondrial function. It also promotes the spontaneous generation of new mitochondria within aging cells, a process known as mitochondrial biogenesis.11,16-18 

How Can Autophagy Be Enhanced?

Autophagy is the cellular cleansing process to dispose of cellular garbage, debris, microorganisms, and unwanted compounds. Enhanced autophagy has been found in exceptionally healthy centenarian humans and appears to be a key target for living a healthier, longer life.19 

To enhance autophagy it is important to reduce the formation of excessive cellular garbage, reduce inflammation, and support mitochondrial function.5 Here are some of the key general measures to support these goals:

  • Exercise, body movement, and diaphragmatic breathing are the key factors that keep autophagy functioning properly in clearing cellular debris and fighting aging. 
  • Eating a health-promoting diet rich in colorful fruit and vegetables, as well as nuts and seeds, and adequate in protein.
  • Avoiding sugar and over-consumption of carbohydrates and calories.
  • Intermittent fasting – one popular method is a daily 16-hour fast with an 8-hour eating window.
  • Regularly consume superfoods like spirulina and other super greens, raw cacao, berries, green tea (particularly matcha), etc.
  • Spice it up! In addition to taking curcumin as a supplement, use other spices and herbs liberally in the diet to take advantage of all of their benefits in fighting inflammation and protecting mitochondria.

Several dietary supplements mentioned above enhance autophagy including curcumin, vitamin D3, fish oils, NAC, ERGO, and CoQ10. Other dietary supplements that promote autophagy include resveratrol and spermidine.20-22 

Resveratrol is a polyphenol compound found in low dosages in grapes (only in skin), red wine, peanuts, and blueberries. Most resveratrol supplements use Japanese knotweed (Polygonum cuspidatum) as the source. Resveratrol enhances autophagy and lowers markers of brain inflammation associated with aging and poor mental function in older adults. As a result, resveratrol improved mood, mental cognition, and scores on measures of activities of daily living in older adults. In other words, it helped them act and feel younger. Improved autophagy is likely one of the key reasons.23-25

Spermidine is a dietary amino acid made in the human body. As its name suggests, spermidine is very important to sperm function, but it also plays a big role in cells throughout the body and as an anti-aging compound. Spermidine fights the aging process by enhancing autophagy as well as the function of mitochondria. Spermidine supplementation has been shown to extend lifespan in aging models and in mice. In humans, maintaining higher spermidine levels through the lifespan appears to contribute to living longer and promotes improved cognitive function.26-28 

Conclusion

One of the remarkable effects of a comprehensive anti-aging and longevity strategy is the power of synergy. The synergistic effects of a multitude of different lifestyle and dietary strategies to slow down the aging process and promote longevity cannot be underestimated. 

Some recent scientific investigations have focused on older adults referred to as "Super Agers" who are aging gracefully with greater mental and physical functioning compared to the norm. They are experiencing “graceful healthy aging and extended longevity.” And that is perhaps the most desired goal for everyone as they move forward later in life. That may be best achieved by adopting a healthy diet and lifestyle along with the use of anti-aging and longevity-promoting dietary supplements. 

Key anti-aging strategies with dietary supplements involve addressing factors like telomere shortening, free radical damage, glycosylation, and mitochondrial function to slow aging and promote longevity.

Maintaining muscle mass is also a major goal in any anti-aging plan. By the time most people reach the age of 80 their muscle mass is a little more than half of what it was in their twenties. The degree of the loss of muscle mass is associated with a significantly shorter life expectancy, decreased vitality, poor balance, slower gait speed, more falls, and increased fractures. Exercise, particularly strength training, is important, along with nutritional strategies such as protein powder supplements and creatine.4,5 

References:

  1. Islam MA, Sehar U, Sultana OF, Mukherjee U, Brownell M, Kshirsagar S, Reddy PH. SuperAgers and centenarians, dynamics of healthy ageing with cognitive resilience. Mech Ageing Dev. 2024 Jun;219:111936.
  2. Guo J, Chen H, Zhang X, et al. The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Oxid Med Cell Longev. 2021 Dec 15;2021:2074610. 
  3. Panigrahi A, Mohanty S. Efficacy and safety of HIMABERB® Berberine on glycemic control in patients with prediabetes: double-blind, placebo-controlled, and randomized pilot trial. BMC Endocr Disord. 2023 Sep 7;23(1):190. 
  4. Strasser B, Volaklis K, Fuchs D, Burtscher M. Role of Dietary Protein and Muscular Fitness on Longevity and Aging. Aging Dis. 2018 Feb 1;9(1):119-132. 
  5. He W, Connolly ED, Cross HR, Wu G. Dietary protein and amino acid intakes for mitigating sarcopenia in humans. Crit Rev Food Sci Nutr. 2024 May 27:1-24.
  6. Richards JB, Valdes AM, Gardner JP, et al. Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. Am J Clin Nutr 2007;86(5):1420-5.
  7. Izadi M, Sadri N, Abdi A, Zadeh MMR, Jalaei D, Ghazimoradi MM, Shouri S, Tahmasebi S. Longevity and anti-aging effects of curcumin supplementation. Geroscience. 2024 Jun;46(3):2933-2950. 
  8. Lapenna D. Glutathione and glutathione-dependent enzymes: From biochemistry to gerontology and successful aging. Ageing Res Rev. 2023 Dec;92:102066. 
  9. Raghu G, Berk M, Campochiaro PA, Jaeschke H, Marenzi G, Richeldi L, Wen FQ, Nicoletti F, Calverley PMA. The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress. Curr Neuropharmacol. 2021;19(8):1202-1224. 
  10. Beelman RB, Kalaras MD, Phillips AT, Richie JP Jr. Is ergothioneine a 'longevity vitamin' limited in the American diet? J Nutr Sci. 2020 Nov 11;9:e52.
  11. Ames BN. Prolonging healthy aging: Longevity vitamins and proteins. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):10836-10844.
  12. Cheah IK, Halliwell B. Ergothioneine, recent developments. Redox Biol. 2021 Jun;42:101868.
  13. Kondoh H, Teruya T, Kameda M, Yanagida M. Decline of ergothioneine in frailty and cognition impairment. FEBS Lett. 2022 May;596(10):1270-1278. 
  14. Kameda M, Teruya T, Yanagida M, Kondoh H. Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility. Proc Natl Acad Sci U S A. 2020 Apr 28;117(17):9483-9489.
  15. Nierenberg JL, He J, Li C, Gu X, Shi M, Razavi AC, Mi X, Li S, Bazzano LA, Anderson AH, He H, Chen W, Guralnik JM, Kinchen JM, Kelly TN. Serum metabolites associate with physical performance among middle-aged adults: Evidence from the Bogalusa Heart Study. Aging (Albany NY). 2020 Jun 1;12(12):11914-11941. 
  16. Jonscher KR, Chowanadisai W, Rucker RB. Pyrroloquinoline-Quinone Is More Than an Antioxidant: A Vitamin-like Accessory Factor Important in Health and Disease Prevention. Biomolecules. 2021 Sep 30;11(10):1441. 
  17. Nakano M, Ubukata K, Yamamoto T, Yamaguchi H. Effect of pyrroloquino- line quinone (PQQ) on mental status of middle-aged and elderly persons. FOOD Style. 2009;21:13(7):50-3.
  18. Harris CB1, Chowanadisai W, Mishchuk DO, et al. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. 2013 Dec;24(12):2076-84.
  19. Kitada M, Koya D. Autophagy in metabolic disease and ageing. Nat Rev Endocrinol. 2021;17(11):647-661.
  20. Pavlova JA, Guseva EA, Dontsova OA, Sergiev PV. Natural Activators of Autophagy. Biochemistry (Mosc). 2024 Jan;89(1):1-26.  
  21. McCarty MF. Nutraceutical and Dietary Strategies for Up-Regulating Macroautophagy. Int J Mol Sci. 2022;23(4):2054.
  22. Brimson JM, Prasanth MI, Malar DS, et al. Plant Polyphenols for Aging Health: Implication from Their Autophagy Modulating Properties in Age-Associated Diseases. Pharmaceuticals (Basel). 2021;14(10):982. 
  23. Truong VL, Jun M, Jeong WS. Role of resveratrol in regulation of cellular defense systems against oxidative stress. Biofactors. 2018 Jan;44(1):36-49.
  24. Koushki M, Dashatan NA, Meshkani R. Effect of Resveratrol Supplementation on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Clin Ther. 2018 Jul;40(7):1180-1192.e5.
  25. Marx W, Kelly JT, Marshall S, et al. Effect of resveratrol supplementation on cognitive performance and mood in adults: a systematic literature review and meta-analysis of randomized controlled trials. Nutr Rev. 2018 Jun 1;76(6):432-443. 
  26. Madeo F, Bauer MA, Carmona-Gutierrez D, Kroemer G. Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans? Autophagy. 2019;15(1):165-168. 
  27. Kiechl S, Pechlaner R, Willeit P, et al. Higher spermidine intake is linked to lower mortality: a prospective population-based study. Am J Clin Nutr. 2018;108(2):371-380.
  28. Schroeder S, Hofer SJ, Zimmermann A, et al. Dietary spermidine improves cognitive function. Cell Rep. 2021;35(2):108985.

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