GLP-1 medications for weight loss and diabetes appear to slow the body’s aging processes, a sign that the blockbuster drugs could ultimately help people live longer. The idea that these medications may extend lifespan isn’t exactly far-fetched; it’s more of an extension of what they’ve already been shown to do. Studies have found that along with helping people shed fat and control blood sugar, GLP-1 drugs improve the health of many different parts of the body, lowering the risk of heart, kidney and liver disease, for example, and reducing sleep apnea and inflammation, which contribute to loss of health and function as people age. “Aging is the biggest risk factor for many diseases, and if we can target aging itself, we might be able to treat all kinds of diseases that are associated with aging,” said Dr. Danica Chen, a professor at the University of California at Berkeley who studies calorie restriction and aging. Now, scientists have turned their attention to biological markers of aging to better understand exactly how GLP-1 drugs may affect the aging process. The new research conducted in mice and people is early, and scientists say they don’t know whether the benefits apply only to people who are overweight or have diabetes when they start taking them medications, or if they could also slow aging in people who are normal weight and otherwise healthy. For that reason, experts say it’s too early for people to use this medication solely in the hopes of living longer. “There are people who are biohacking and taking these agents who are not either diabetic or obese, and the question there is what happens in lean younger non-diabetic individuals, especially over the long term,” said Dr. James Kirkland, who directs the Center for Advanced Gerotherapeutics at Cedars-Sinai Medical Center in Los Angeles. “My concern is that people could overread some of this stuff.” Kirkland says the metrics used in the new studies – which are based on measurements of epigenetics, the way genes are turned on and off in the body and the measures of proteins our bodies make over time — are still in development, and although they’re useful for studies in larger groups of people, they’re not very informative for individuals, though many companies have begun marketing these types of tests to curious consumers. “They can vary tremendously from day to day within a person,” Kirkland said. Measuring biological clocks Still, these early findings are generating excitement. “We’re seeing a reduction in age,” somewhere around three to six years, said Dr. Kevin Duffin, vice president of aging research at Eli Lilly. Lilly makes tirzepatide, which is sold as Zepbound for weight loss and Mounjaro for diabetes management. “It’s not the panacea. It’s not like we’re going to reduce age by 30 years or something, but it’s a significant reduction,” Duffin told a packed audience at the recent Aging Research and Drug Discovery conference in Boston. Duffin presented new data from Lilly’s Surmount V clinical trial, which randomly assigned more than 700 adults who were overweight but did not have diabetes to use either tirzepatide or semaglutide for 72 weeks. The aging study looked at a group of 71 participants from the study who were on tirzepatide and over the age of 50. By measuring how certain genes in their blood were turned off and on during the course of the study, the researchers were able to look at changes to so-called epigenetic clocks, which reveal the biological age of their organs and tissues, as opposed to their calendar age. Over the course of the study, Duffin explained, they would have expected a person to age 1.38 years in chronological time. But in the small group of study participants who were using tirzepatide, biological clocks advanced more slowly. Across different types of epigenetic clocks, the researchers saw an average change of between 1.1 years and 0.7 years in biological aging. Some biological clocks actually went backward, suggesting that some organs and tissues were acting younger than when people started the study. Duffin acknowledged that the study has limitations. There was no placebo group who were not using any weight loss meds to compare against the people on tirzepatide, for example, and the follow-up was relatively brief. From what the researchers could see, the anti-aging effects seemed to get stronger over time, however, so they hope to follow people for longer in the next trial. “Be very interesting to see what happens at four or five years after treatment with a GLP-1,” Duffin said. It’s also not yet clear whether the slowing of the biological aging is due to weight loss or if there could be some effect of the GLP-1 drugs independently. There’s a lot of good evidence, for example, that eating a calorie-restricted diet — cutting calories by about 25 per cent — has anti-aging effects and extends the lifespan of many types of animals. Studies have shown that weight loss surgery, which helps people drop significant amounts of weight, slows biological aging, too. But it’s very hard to achieve weight loss or cut calories that much through willpower alone, making the role of medications and surgery critical. In one of the first questions after his talk, an audience member asked Duffin whether he had repeated the experiment in someone who was not overweight, to see if the effect was a result of weight loss or something else the drug was doing. “We get this question all the time,” Duffin said. “The bottom line is, these drugs work through [blood sugar] reduction and through weight loss, and the effects we’re seeing are mostly due to that.” Benefits beyond weight loss The drug semaglutide, which is sold as Wegovy and Ozempic, shows many of the same anti-aging benefits, according to new research from drugmaker Novo Nordisk. By measuring changes to proteins in the body over time in people using semaglutide, the company’s scientists found that it reduced the heart’s biological age by two to four years compared with a placebo, and it reduced the age of organs such as the lung, kidney, brain and pancreas by one to four years. The study was published as a preprint, ahead of peer review. The researchers said the effects were not completely explained by weight loss, blood sugar control or inflammation. Study author Dr. Alejandro Aguayo-Orozco, senior global director of cardiometabolic research and development at Novo Nordisk, said the benefits of GLP-1 medications had thus far been measured one disease at a time – but what if the effects were bigger than that? “If we’re touching so many diseases, are we actually also touching something that is systemic across these diseases? Is it aging? Is it health span?” he asked at the recent Aging Research and Drug Discovery meeting. Recent research in mice tried to answer some of these questions more directly. Mice typically live about two years, so it’s easier to follow them throughout their lifespan than it is to do the same for humans. Scientists at the University of California at Berkeley took 20-month-old mice – roughly the age equivalent of 60-year-old humans – and gave them injections of semaglutide or a placebo for the rest of their lives. They were roughly the same body weight at the start of the study. But the mice on semaglutide ate less and lost weight, and they lived longer than the mice that got placebo injections. The semaglutide-treated mice had an average lifespan of 834 days, about the same as 80 human years, while the mice injected with placebos lived 742 total days, or roughly 75 human years. To test whether it was the weight loss or the drug specifically that was responsible for the benefit, researchers next reduced the amount of calories fed to another group of mice by 25 per cent — about the same amount of reduction seen in mice on semaglutide. Like the GLP-1-treated mice, the calorie-restricted mice lived longer, but there were some differences between the two groups, said Chen at UC Berkeley, who helped lead the research, which was published in the journal Nature. For many tissue functions the group looked at, especially related to muscle function and mobility, the semaglutide-treated mice and calorie-restricted mice performed about the same. But mice on semaglutide showed some advantages. They functioned better at thinking and at finding their way out of a maze, and they were better able to manage their blood sugar than mice on calorie restriction alone. “So that just means that it’s more than just a calorie restriction and has additional benefits,” Chen said. By Brenda Goodman, CNN
