How are scientists measuring and supporting longevity?

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According to the U.S. Census Bureau, Americans are living longer than ever. In fact, between 1960 and 2015, life expectancy increased by almost 10 years. Americans could gain roughly six years more, with lifespans expected to reach 85.5 years on average by 2060. As a result, says InsideTracker (Cambridge, MA) cofounder and chief scientific officer Gil Blander, the definition of aging has shifted dramatically as people focus on enjoying an active lifestyle and good health well into their golden years. “The conversation is changing from ‘lifespan’ to ‘healthspan,’” he says. “We are asking how we can feel as vital and good throughout our extended lives, and how best to optimize our health for as long as possible.”

The challenge is determining exactly how to measure healthy or unhealthy aging. “Longevity brands must demonstrate, in human trials, that they can slow, stop, or reverse biologic aging, as measured by a clinically relevant, scientifically accepted aging biomarker,” says Tom Weldon, founder and CEO at Ponce de Leon Health (Fernandina Beach, FL). “No one can afford to run a randomized, placebo-controlled, double-blind human study and wait until all subjects have expired. It is simply not practical, so using scientifically accepted, validated biomarkers is the only realistic endpoint for longevity human trials.”

Here are some tests—and ingredients—on the radar for today’s longevity specialists and suppliers.

Trending Tests and Biomarkers

Blood testing: Tried and true, as well as affordable and widely accessible, blood tests for kidney, liver, and immune function still provide great insight into the aging process. Life Extension (Fort Lauderdale, FL) Director of Education Michael A. Smith recommends that blood sugar markers like fasting glucose, fasting insulin, and hemoglobin A1C should always be included as well, since glycation (when glucose binds to the body’s proteins) accelerates whole-body aging. If cardiovascular and inflammation are of top concern, apolipoprotein B, LDL, C-reactive protein, and homocysteine should be assessed. “Additional biomarkers to consider are markers for endocrine health, including thyroid, growth hormones, and steroid hormones,” Smith adds.

Stool testing: Thanks to rising interest in the microbiome, stool analysis is becoming a valuable tool for brands and consumers seeking to connect the dots between gut bacteria and overall health. “Studies show very different changes in bacteria phyla populations with aging,” Smith explains. “As an example, the decline of Bifidobacteria with age may contribute to aging-associated disease.”¹

Metabolic indicators: Since metabolic syndrome is a prominent indicator of aging, Blander says that testing for ingredients’ impact on blood pressure, blood sugar, excess body fat around the waist, and high cholesterol levels is one way to measure impact on aging.

DNA and mitochondrial testing: DNA methylation (DNAm) testing measures how capable the body is at turning on genes that lead to good health and turning off genes that lead to poor health. Ponce de Leon Health recently utilized this method in a new study on Rejuvant, a patent-pending, timed-release CaAKG (calcium alpha-ketoglutarate) supplement plus vitamin A for men and vitamin D for women, which showed that subjects taking the ingredient for an average of seven months exhibited an average decrease in biological age by eight years.²

Another way this method is being used is to determine impacts on muscle health. Young adults tend to have mitochondria in their muscles that are highly ordered in their distribution; however, as we get older, that natural order starts to break down, explains Chris Hopkins, chief scientific officer of Nutra Biosystems, a division of InVivo Biosystems (Eugene, OR). “Autophagy and mitophagy deficiencies creep in over the years, and that nice mitochondrial pattern of our youth becomes more chaotic as they cause your mitochondria to become unhealthy: bloated with enlarged blobs of ineffectively recycled buildup, and starting to exhibit reduced oxidative function and ATP production,” he adds. Researchers are beginning to look at a compound’s ability to boost the retention of the striated distribution pattern of youthful muscle in order to stall sarcopenia and allow healthy muscle strength to continue.

Because these changes in gene expression can be expensive to track in humans, customers of InVivo Biosystems are attracted to its preclinical platform, where they can screen formulations for optimal effect in alternative modeling systems (specifically, C. elegans, zebrafish, and differentiated stem cell tissue).

Trending Ingredients

Enzymes: Those that promote healthy aging seem to be AMPK and sirtuins, says Smith. “These are not the familiar digestive enzymes found in the GI tract; instead, these are enzymes found inside of our cells that regulate aging,” he says^3,4, and are found in herbs like Gynostemma pentaphyllum and hesperidin, the polyphenol concentrated in orange peels. The goal, then, is to ramp up AMPK and sirtuin activity to promote more youthful cellular function.

Resveratrol: Resveratrol is a known blood glucose regulator, but new research shows it can also activate sirtuins.

Turmeric/curcumin: “Turmeric/curcumin supplements can reduce inflammatory cytokines, oxidative stress, and hsCRP, all factors that, when high, are correlated with aging,” explains Blander. “In addition, curcumin’s polyphenolic properties reduce inflammation levels, measured by the biomarker hsCRP, associated with age-related conditions such as metabolic syndrome and diabetes.”

Pro-autophagy ingredients: Autophagy is the process by which cells clear out damaged proteins and other waste, and this process is linked to a healthy lifespan.⁵ According to Smith, two ingredients that promote autophagy are piperlongumine, a compound isolated from the long pepper plant, and luteolin, a flavonoid found in parsley.

Antioxidants: From fisetin (a flavonoid found in fruits and vegetables) to vitamin D, antioxidants are still trending when it comes to longevity.

References

1. Hopkins MJ et al. “Age and disease and related changes in intestinal bacteria populations assessed by cell culture, 16S rRNA abundance, and community cellular fatty acid profiles.” Gut, vol. 48, no. 2 (February 2001): 198-205
2. Demidenko O et al. “Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test.” Aging, vol. 13, no. 22 (November 30, 2021): 24485-24499
3. Burkewitz K et al. “AMPK at the nexus of energetics and aging.” Cell Metabolism, vol. 20, no. 1 (July 1, 2014): 10-25
4. Greiss S et al. “Sirtuin/Sir2 phylogeny, evolutionary considerations and structural conservation.” Molecules and Cells, vol. 28, no. 5 (November 30, 2009): 407-415
5. Hansen M et al. “Autophagy as a promoter of longevity: Insights from model organisms.” Nature Reviews: Molecular Cell Biology, vol. 19, no. 9 (September 2018): 579-593