How Do Supplements Support Longevity?

November 9, 2025

Welcome to Issue 156 of Science Says! Our weekly newsletter where you’ll learn the latest healthy aging and C15:0 research news that our team of doctors, scientists, and experts are most excited about—without having to go search for it.

Eric and Steph
Co-Founders, Doctors, Nerds

What Dr. Stephanie Venn-Watson, our co-founder and author of The Longevity Nutrient and over 80 peer-reviewed scientific publications, is reading.

Healthy Aging

Your Checklist for Geroprotectors

Longevity is a hot topic. Which is no surprise, since we all want to live as healthy as possible, as long as possible. As a result, more and more supplements are figuring out where they might fit in the longevity and healthy aging space. This week, to help build out your optimal healthy aging supplement regimen, we provide an easy-to-use checklist for ideal geroprotectors…and of course, how C15:0 stacks up.

Great! What is a geroprotector?

Good question. As described by Moskalev et al., a geroprotector is a molecule that can slow the rate at which we age to keep us as healthy as possible, for as long as possible. In the longevity science world, geroprotectors are considered the holy grail of healthy aging because they often provide meaningful health benefits that can be seen and felt within months. Which is good, because taking a supplement and simply waiting to see if one simply lives longer can be much less rewarding.

Your geroprotector (aka longevity) checklist.
First, it’s important to understand that no single supplement is going to take care of everything everyone needs to live a long and healthy life. We are wonderfully complex and special individuals who have different needs and different goals at different ages.

Additionally, we would be remiss to not cover the non-supplement must-haves for health and longevity:

A healthy diet, with the Mediterranean diet having the most robust long-term scientific support.
Healthy sleep, including not too little…and not too much. In general, around 7 to 8 hours seems to be the sweet spot.
Healthy activities that are both aerobic and resistance-based, ideally by finding activities that you enjoy (breakdancing, anyone?).
A healthy social life with family and friends, including the furry kind. Really. Friedmann et al. showed that, in a longitudinal study with people 50 years or older, those who had pets maintained better cognitive and physical function than those who did not have regular contact with pets.

With that, we can move onto supplements.

Your geroprotector (aka longevity) supplement checklist.

Here are six important criteria for ideal geroprotective supplements:

1.Targets the Human Longevity Regulating Pathway. This well-studied pathway (provided below) is based on the understanding of how caloric restriction extends longevity in multiple species. It includes the insulin/IGF-1 signaling (IIS), AMPK, mTOR, and/or sirtuin (SIRT1) pathways.

2. Reverses multiple hallmarks of aging. Hallmarks of aging are processes that define how we age at the cellular level. Molecules that can slow or reverse these processes can help slow or reverse aging-related breakdown. The 12 hallmarks of aging, as described by Lopez-Otin et al., are provided below.

3. Has evidence of slowing aging rates. If a molecule can effectively slow the rate at which we age, we can achieve a biological age that is younger than our chronological age. Two gold-standard measurements of aging rates and biological age are called AgeAccelPheno and AgeAccelGrim. AgeAccelPheno is based on nine blood biomarkers identified by Levine et al., of which higher red blood cell distribution width (RDW) is the strongest predictor of older biological age (aka, accelerated aging rates, see below). AgeAccelGrim, as described by Lu et al. includes 12 protein-based biomarkers of DNA methylation.

4. Directly supports biomarkers of healthy aging within months. Controlled intervention studies, including in vivo efficacy studies and clinical trials should support that the molecule has direct beneficial effects on biomarkers of long-term health within months, not decades.

5. Has evidence of supporting long-term health in human populations. In addition to all of the above, robust prospective cohort studies with large and diverse human populations should repeatedly provide evidence that a geroprotector protects biomarkers of long-term heart, cognitive, and metabolic health in diverse populations.

6. Is safe to take routinely for decades. Geroprotectors are likely needed throughout decades of our life, requiring a given geroprotector to be safe to take for long periods of time and at all ages.

How C15:0 stacks up on the geroprotector list.

C15:0, an odd-chain saturated fatty acid, is indeed emerging as a core geroprotector. Here’s how peer-reviewed studies are helping C15:0 make its way through the geroprotector checklist:

C15:0 targets the Human Longevity Regulating Pathway. By activating AMPK and inhibiting mTOR, multiple studies have shown that C15:0 targets the heart of the Human Longevity Pathway.
C15:0 reverses multiple hallmarks of aging. This includes improving mitochondrial function in both cell-based and whole-body systems, improving cellular signaling, and balancing aging-related immune responses in relevant models.
C15:0 has evidence of slowing aging rates. C15:0 has been shown to directly lower a key biomarker of biological aging (aka, RDW) in multiple models. Further, Liu et al. showed that people with higher C15 in complex lipids have a younger biological age than their chronological age using both AgeAccelPheno and AgeAccelGrim.
C15:0 directly supports biomarkers of healthy aging within months. C15:0 supplementation has been shown to support metabolic, red blood cell, cardiometabolic, gut, liver, and immune health in multiple animal models. Early signs of similar benefits are emerging from 12-week human clinical trials, including supported liver and red blood cell health.
C15:0 has evidence of supporting long-term health in large and robust human population studies. Meta-analyses of large prospective studies following tens of thousands of people over many years repeatedly show that people with higher C15:0 have better long-term health, especially cardiovascular and metabolic health.
C15:0 Is safe. As a beneficial fatty acid that humans get at birth from mom’s milk and throughout our lives in dairy products, C15:0 has been shown to be safe throughout all life stages.
As an extra-credit checkmark for C15:0, this nutrient also physically strengthens cell membranes against lipid peroxidation, tapping into the Cell Membrane Pacemaker Theory of Aging. This theory shows that stronger fatty acids in cell membranes (aka fewer double bonds) result in lower systemic lipid peroxidation and longer mammalian lifespan.

That’s 7 out of 6…not bad for this little but crucial nutrient. With 100+ peer-reviewed studies and an average of 1 new paper on C15:0’s health benefits being published per week, there’s still a lot more to come.