Living Longer: The Best Supplements for Increasing Longevity

Society has idolized the fountain of youth since the Greek historian Herodotus first wrote about it in the 5th century, and it has been endeared in plays, books, and movies ever since. Though the fountain of youth as first described may not be more than legend, recent research touts some promising longevity-promoting supplements you may not be familiar with.

What is aging?

Aging is a biological process that primarily occurs from the accumulation of cellular damage from free radicals, gene changes, improper cell cycles, mitochondrial dysfunction, and shortening of chromosome ends, called telomeres.

Helpful terms

• Anti-Aging. This marketing term describes the properties of an intervention, supplement, product, or food that significantly slows down the rate of, but does not stop, natural aging.
• Autophagy. This is a built-in mechanism that detoxes and eliminates damaged cellular material and debris from the body. Research has found that fasting, ketosis, and specific substances can promote autophagy.
• Centenarian. Individuals who live to at least 100 years old. As of 2021, there are over 500,000 centenarians worldwide, with the majority living in the USA, Japan, France, Spain, and Italy. Researchers anticipate the number of centenarians to increase as research and medical care continue improving. Healthspan: Refers to the quality of life through the aging process, often defined as how long an individual is healthy. This often means delayed or avoided chronic disease, symptoms, and disability.
• Lifespan. Refers to the lifetime or number of years an individual or organism lives. Life expectancy is slightly different, as it is the statistical measure of the average expected lifespan based on individual factors.
• Longevity. This is the most commonly used term by scientists that refers to both the quality (healthspan) and quantity of years (lifespan) of an individual’s life. Longevity science refers to the study of promoting a longer, healthier life.
• Sirtuins. A family of seven genes (SIRT1-SIRT7), which code proteins that regulate cellular aging, death, and response to stress.

The science

Some of the most well-known longevity researchers include Dr. Valter Longo, Dr. David Sinclair, Dr. Thomas Perls, Dr. Nir Barzilai, and Dr. Mark Mattson. All have studied the effects of fasting, specific supplemental and prescription substances, calorie restriction, and a combination of these in animals and humans on mitochondrial function and autophagy.

Popular longevity podcasts include those of Rhonda Patrick, Ph.D., and Dr. Peter Attia. Drs. Perls and Barzilai have researched the lives and communities of centenarians, such as in the New England Centenarian Study, to extrapolate helpful lifestyle practices and diets. Recently, Dr. David Sinclair released a podcast series where he discusses the most important longevity issues including longevity molecules and drugs, a specific anti-aging lifestyle, and the positive influence of saunas and ice baths.

The best longevity supplements

While supplements alone won't turn you into a centenarian, evolving research shows one or more of the supplements below may influence your lifespan, and help you age more gracefully.

Supplement quality is paramount. The highest quality supplement brands carry the GMP label – Good Manufacturing Practices - and are third-party tested by either Consumer Lab or NSF.

• Nicotinamide mononucleotide (NMN). According to research, NMN is the main supplement to slow down aging. The effect of NMN was shown in several animal-based studies, revealing that regular consumption of NMN slows down the deterioration of cells. In addition, research shows it offers cardio and neuroprotection. At a cellular level, NMN boosts NAD+ molecules, which play the main role in the cell cycle. Unfortunately, in humans, the concentration of NAD+ molecules is reduced with age. The NMN supplement can help control this biological mechanism and stabilize the NAD+ molecule.
• Metformin or berberine. Metformin is better known as an anti-diabetic drug that reduces glucose levels in the blood. Preclinical studies in animals have shown that metformin could be a significant anti-aging drug that may also extend lifespan. There are two large ongoing clinical trials (MILES and TAME) trying to prove the potential benefit of metformin as a longevity drug. However, there are several controversial opinions that metformin as an anti-diabetic drug should not be used for people who don’t have diabetes. Berberine is a herbal compound that could be used as an alternative to metformin. Several studies indicated that berberine could regulate glucose levels in the same way as metformin. In comparison with metformin, berberine has fewer side effects and is more tolerable.
• CD38 biological pathway inhibitor. There are three main supplements called CD38 inhibitors: quercetin, apigenin, and fisetin. They belong to the flavonoid group, which is found in plants. In the human body, the CD38 biological pathway blocks NAD+ and reduces its concentration. It is a natural process and with age, it becomes more intense. Longevity scientists suggest blocking the CD38 molecule using quercetin, apigenin, and fisetin. The result of using CD38 inhibitors is increasing NAD+ concentration despite aging.
• Reduced NMN, IRW, PNGL. These are new innovation supplements for longevity. Reduced NMN is a compound that could make NAD+ levels several times higher compared to simple NMN. Interestingly, reduced NMN could stabilize NAD+ levels for 24 hours. More clinical studies are needed for this supplement to become available on the market. IRW and PNGL are natural compounds found in eggs and a plant called notoginseng. These two are called new-era NAD+ boosters.
• Resveratrol. This polyphenic compound found in grapes and dark berries has been one of Dr. David Sinclair’s primary research areas. He has taken 1.0 grams of trans-resveratrol daily since 2004 mixed in a few spoonfuls of full-fat Greek yogurt. He explains it works by mimicking fasting in the body, and turning on autophagy activates a longevity sirtuin 1 gene, SIRT1. Interestingly, resveratrol works together with NMN. Resveratrol only has this biological role only when there are enough NAD+ molecules in the organism. So, NMN is needed to boost NAD+, opening the gates for resveratrol and its biological power.
• Sulforaphane. This compound is found in cruciferous vegetables, especially broccoli sprouts, and has shown significant health benefits such as improving inflammation, protecting cellular health, and modulating gene activity. Sulforaphane inhibits DAF- 2/insulin/IGF-1 signaling and activates DAF- 16/FOXO nuclear transcription pathways. The result is a prolonged lifespan with greater health. It is a highly unstable, rapidly degradable compound. For this reason, Dr. Rhonda Patrick recommends choosing a brand that contains glucoraphanin, the precursor to sulforaphane, as well as myrosinase, an enzyme that helps convert glucoraphanin to sulforaphane. The gold standard supplement containing stabilized sulforaphane is Prostaphane, a product only available in Europe. Dr. Ingrid Herr published the first research proving the effect of this longevity compound in 2021. Still, more results based on research using model organisms and human clinical trials are needed.

Common questions and concerns

1. Will a supplement work better than a food or lifestyle choice? A healthy lifestyle is always important for overall health, but longevity supplements can perform biological functions that cannot be replicated by healthy eating alone. In addition, some longevity supplements create reactions in the body that healthy foods are simply unable to recreate. An example is resveratrol mimicking fasting in the body, thus turning on autophagy and activating longevity genes.

2. Do I need a supplement if I eat and live healthily?
It depends. There may be gaps between your lifestyle and genetics that predispose you to certain outcomes. A supplement, or combination of supplements, may be able to improve these outcomes. In addition, to obtain the longevity benefits these substances impart, you must consume a much higher concentration than could often be obtained from the diet.

3. Are there other important supplements for my health?
Yes, this list does not encompass every possible beneficial supplement for you. Other supplement examples that may help you look and feel your best include Magnesium, Omega-3s, Vitamin D, biotics, digestive enzymes, and fiber.

Summary

While supplements exclusive to healthy lifestyle behaviors are no panacea, some substances can promote longevity and support healthy aging. It’s unlikely you need or should take every supplement listed here. Work with your doctor and dietitian to determine what supplement, if any, is right for you.