Why We May Soon Add ‘Antiaging’ to GLP-1s’ Growing Benefits

Longevity researcher Coleen Murphy, PhD, remembers all the handwringing among her colleagues over muscle loss when GLP-1s were first making waves. Now, that caution has flipped to fervor, as researchers push to study GLP-1s’ impact on aging through an unprecedented approach: testing the drugs in “healthy” people.Coleen Murphy, PhD“At first there were people in the longevity field who said [GLP-1s] are not very important for aging and longevity,” Murphy said. “But then clinical trial after clinical trial was showing that the people who have been put on GLP-1s are doing better in ways that no one was anticipating.” It has “really thrown the field,” she said, because the research isn’t officially about aging.No large pharmaceutical companies have expressed interest in testing GLP-1s in healthy people, but trials are emerging through private startups and academic groups.The latest one — from Vero Bioscience in partnership with the concierge clinic Atria Health and Research Institute— is recruiting 50- to 75-year-olds with “stable medical status,” according to the listing on clinicaltrials.gov. Participants in the treatment arm will take tirzepatide for 6 months, capped at 10 mg per week, and the primary outcome is brain age as measured by the proteomic aging tool developed by Vero Bioscience co-founder Tony Wyss-Coray, PhD, professor of neurology and neurological sciences at Stanford Medicine in Stanford, California. The estimated trial enrollment, including the control group, is 22 people.Tony Wyss-Coray, PhDA larger study launching later this year in Switzerland — the PROMOTE trial — will include 180 people aged 50-70 years who are “generally healthy” but have at least two risk factors: borderline hypertension, overweight or increased waist circumference, prediabetes, an unfavorable lipid profile, or low-grade inflammation. The double-blind, placebo-controlled trial will track people’s progress for a year using brain scans, inflammatory markers, four DNA methylation clocks, and Vero Bioscience’s proteomic technology. The specific drug hasn’t been selected yet.“Our hypothesis is that GLP-1 receptor activation may influence interconnected metabolic, inflammatory, and vascular pathways relevant to brain aging,” said Heike Bischoff-Ferrari, MD, MPH, DrPH, one of the trial’s researchers and director of the Swiss Campus for Healthy Longevity at the University of Basel in Basel, Switzerland. “However, ‘generally healthy’ does not mean ‘without risk.’ Our goal is to generate rigorous evidence about whether this intervention changes brain-aging measures and whether those changes have functional relevance.”Defining the EndpointWith the development in recent years of aging clocks, the field has wrestled with what to do with them and how to define its endpoint: Is longevity about preventing disease or prolonging function? The question is important, especially for healthy people.Jamie Justice, PhDIn community focus groups conducted by Wake Forest University researchers, participants revealed they wouldn’t take a daily pill that prevented disease — even if the pill was free, according to Jamie Justice, PhD, executive director of the XPRIZE Healthspan competition and an adjunct assistant professor of gerontology and geriatric medicine at Wake Forest University School of Medicine in Winston-Salem, North Carolina.“But when you turned it around and asked, ‘What if you could see a benefit from taking this?’ participants responded very differently,” Justice said. They talked about maintaining cognitive function, staying active with their families, playing with grandkids, and being able to independently go to the grocery store.For Wyss-Coray, the point is not to seek a fountain of youth but rather to slow aging in specific organs — or to return those organs to a more age-appropriate physiologic state. “You have your Mazda — a regular car — and you fix it, then it works again like that Mazda, but it doesn’t start working like a Ferrari,” Wyss-Coray said.Under his hypothesis, people whose organs are shown to be of normal “healthy” age wouldn’t see benefits from taking a GLP-1. But the drugs may benefit those who appear healthy on an annual exam but have an organ — perhaps the heart or a lung — that’s quietly aging faster than it should. He hopes to examine which proteins drive aging in individual organs and to use those findings to develop a drug intervention. Maybe that intervention is a GLP-1.Wyss-Coray reported being a scientific officer and co-founder of Teal Omics and Vero Bioscience, which are both working to commercialize aspects of his research. Murphy is co-founder of VerElle Health, a reproductive aging and diagnostics women’s health company. The other sources in this article did not provide any relevant financial disclosures.