San Francisco, September 26 — Longevity science has moved a long way from speculation. Researchers have spent three decades identifying the biological mechanisms and lifestyle factors that influence how long humans live, and the field’s founding moment came in this city. In 1993, Cynthia Kenyon, a molecular biologist at the University of California, San Francisco, published findings in Nature showing that a single gene mutation in the roundworm Caenorhabditis elegans could double its lifespan.
The result demonstrated that aging is not immutable. It can be regulated by specific genes.
That discovery opened a line of inquiry that continues today. Subsequent research identified the insulin/IGF-1 signaling pathway as a conserved regulator of aging across species, from yeast to mammals.
From Worms to Monkeys to People
Chemical compounds followed. In 2003, scientists found that resveratrol, a compound in red wine, extended lifespan in yeast and later in mice. Human trials have yielded mixed results.
Caloric restriction has held up more consistently in animal models. A 2017 study in Nature Communications reported that rhesus monkeys on a 30% reduced-calorie diet lived significantly longer than controls.
In humans, the CALERIE trial, run between 2007 and 2012, showed that moderate caloric restriction improved metabolic markers but did not yet prove lifespan extension. Telomeres drew wide attention after Elizabeth Blackburn, Carol Greider and Jack Szostak won the 2009 Nobel Prize in Physiology or Medicine for discovering how chromosomes are protected by telomeres and the enzyme telomerase. Telomere shortening is associated with cellular aging, but its relationship to overall lifespan is complex.
In 2013, researchers at Harvard Medical School reported that NAD+ levels decline with age and that boosting them with a compound called NMN improved health in mice. Commercial interest in NAD+ supplements followed.
Human evidence remains preliminary.
What the Trials Are Testing
The TAME trial, Targeting Aging with Metformin, launched in 2015 to test whether metformin, a diabetes drug, can delay age-related diseases in humans. Results are pending. Genetic studies of centenarians have identified variants that correlate with exceptional longevity, including APOE2 and FOXO3.
The New England Centenarian Study, founded in 1995, is among the efforts behind that work. Lifestyle still carries substantial weight.
A 2018 study in Circulation found that five healthy habits — never smoking, maintaining a healthy body mass index, regular exercise, moderate alcohol intake and a healthy diet — could extend life expectancy by more than a decade. The World Health Organization projects global life expectancy at birth will reach 73.4 years by 2025, up from 72.6 years in 2019. The United Nations estimates that by 2050, one in six people will be over 65.
The encouraging part is that the research base is deepening. The caution is that no intervention has been proven to extend maximum human lifespan beyond the documented record of 122 years, set by Jeanne Calment, who died in 1997.
Researchers caution against anti-aging hype and emphasize that rigorous clinical trials are needed before any treatment can be recommended. The National Institute on Aging, part of the US National Institutes of Health, funds much of this work, with an annual budget of approximately US$3.9 billion in 2023. Watch for the TAME results and further human data on caloric restriction and NAD+ compounds.
Until then, patients should treat supplement marketing with skepticism and talk to their doctor before starting anything. Consult your doctor for medical advice.
