Dozens of therapies targeting the biology of aging are approaching clinical trials in humans, but reliable ways to quickly determine whether they actually slow aging processes have been lacking.
Researchers at Yale School of Medicine have proposed a systematic approach: they tested more than one hundred epigenetic biomarkers based on DNA methylation in fifty-one studies of interventions in humans.
The list included caloric restriction, intermittent fasting, exercise, Mediterranean and plant-based diets, metformin, semaglutide, rapamycin, anti-TNF therapies, bariatric surgery, smoking cessation, and other approaches.
The scientists did not ask whether a specific intervention slows aging, but rather looked for which biomarkers consistently capture biological changes after a wide variety of exposures.
It turned out that many aging clocks predict future risks well, but only a small fraction of them respond noticeably to interventions.
Markers measuring the pace of aging or predicting mortality proved to be the most sensitive—they were the ones that most often changed after interventions.
The results were compiled into an open platform called TranslAGE and an interactive website TranslAGE.io, where any researcher can compare the response of more than one hundred biomarkers across more than fifty studies.
Lead author Raghav Sehgal noted that the field has accumulated many biomarkers and even more candidate therapies, but until now there has been no rigorous basis for selecting those suitable as trial endpoints.
Senior author Albert Higgins-Chen added that choosing the right biomarker is no less important than choosing the intervention itself, and the new map will help avoid unnecessary tests and false conclusions.
The work is published in Nature Medicine and relies on data collected in part with support from the U.S. National Institute on Aging.
Imagine a laboratory where dozens of different clocks sit on a shelf: some show the exact time but do not notice when you move the hands, others react to the slightest change but confuse minutes and hours.
The new map helps to understand which of these 'clocks' actually register a shift after an intervention, and which remain indifferent.
This does not promise an immediate breakthrough in extending life, but rather creates a tool without which large-scale geroscience trials risk remaining fragmented and difficult to compare.
Ultimately, the field gains the ability to more quickly weed out ineffective approaches and focus on those that truly change the biology of aging.
