GLP-1 drugs for weight loss and diabetes appear to slow the body’s aging processes, a sign that these blockbuster drugs could ultimately help people live longer.
The idea that these drugs could extend lifespan is not really far-fetched; rather, it is an extension of what they have already done. Studies have shown that in addition to helping people lose fat and control their blood sugar, GLP-1 medications improve the health of many different parts of the body, such as reducing the risk of heart, kidney, and liver diseases, 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 may be able to treat all sorts of diseases associated with aging,” said Dr. Danica Chen, a professor at the University of California, Berkeley who studies calorie restriction and aging.
Today, scientists are turning to biological markers of aging to better understand exactly how GLP-1 drugs may affect the aging process.
The new research in mice and humans is early, and scientists say they don’t know whether the benefits apply only to people who are overweight or diabetic when they start taking the drugs, or whether they could also slow aging in normal-weight, healthy people.
For this reason, experts believe that it is too early for people to use this drug solely in the hope of living longer.
“There are people who are biohacking and taking these agents who are neither diabetic nor obese, and the question is what happens in young, lean people who are not diabetic, especially over the long term,” said Dr. James Kirkland, who directs the Center for Advanced Gerotherapeutics at Cedars-Sinai Medical Center in Los Angeles. “What worries me is that people might overinterpret some of this. »
Kirkland says that the measurements used in the new studies — which are based on measurements of epigenetics, how genes are turned on and off in the body, and measurements of the proteins our bodies produce over time — are still in development, and while they are useful for studies of larger groups of people, they are not very informative for individuals, although many companies have begun marketing these types of tests to curious consumers.
“They can vary wildly from day to day in a person,” Kirkland said.
However, these first discoveries arouse enthusiasm.
“We’re seeing a reduction in age,” between three and six years, said Dr. Kevin Duffin, vice president of aging research at Eli Lilly. Lilly makes tirzepatide, sold as Zepbound for weight loss and Mounjaro for diabetes management.
“It’s not a panacea. It’s not like we’re going to reduce the age by 30 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 overweight but non-diabetic adults to use tirzepatide or semaglutide for 72 weeks. The Aging Study looked at a group of 71 study participants who were taking tirzepatide and were over the age of 50.
By measuring how certain genes in their blood were turned on and off during the study, the researchers were able to observe changes in so-called epigenetic clocks, which reveal the biological age of their organs and tissues, as opposed to their calendar age.
During 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 used tirzepatide, body clocks moved more slowly. Across different types of epigenetic clocks, researchers found an average change in biological aging of between 1.1 years and 0.7 years. Some biological clocks actually went back, suggesting that some organs and tissues were acting younger than when the study began.
Duffin acknowledged that the study had limitations. There was no placebo group using any weight-loss medication to compare to those on tirzepatide, for example, and follow-up was relatively brief.
From what the researchers have seen, however, the anti-aging effects seem to increase over time, so they hope to follow people for longer in the next trial.
“It will be very interesting to see what happens four or five years after treatment with a GLP-1,” Duffin said.
It is also unclear whether the slowing of biological aging is due to weight loss or whether GLP-1 drugs might have an independent effect. For example, there is plenty of strong evidence that a low-calorie diet (reducing calories by about 25%) has anti-aging effects and extends the lifespan of many types of animals.
Studies have shown that bariatric surgery, which helps people lose significant amounts of weight, also slows biological aging. But it is very difficult to lose weight or reduce calories that much through willpower alone, making the role of medications and surgery essential.
In one of the first questions after his speech, an audience member asked Duffin if he had repeated the experiment on a person who was not overweight, to see if the effect was the result of weight loss or another effect of the drug.
“We get this question all the time,” Duffin said. “Ultimately, these drugs work by reducing (blood sugar) and losing weight, and the effects we see are primarily due to that.”
The drug semaglutide, sold under the names Wegovy and Ozempic, has many of the same anti-aging benefits, according to a new study from drugmaker Novo Nordisk.
By measuring changes in proteins in the body over time in people using semaglutide, the company’s scientists found that it reduced the biological age of the heart by two to four years compared to a placebo, and that it reduced the age of organs such as the lungs, kidneys, 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 entirely 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 drugs had so far been measured on a disease-by-disease basis – but what if the effects were larger than that?
“If we’re affecting so many diseases, are we also affecting something that is systemic in these diseases? Is it aging? Is it life expectancy?” he asked at the recent Aging Research and Drug Discovery meeting.
Recent research in mice has attempted to answer some of these questions more directly. Mice typically live about two years. It is therefore easier to follow them throughout their lives than to do the same for humans.
Scientists at the University of California, Berkeley took mice aged 20 months – roughly the equivalent of a human age of 60 – and gave them injections of semaglutide or a placebo for the rest of their lives.
They were about the same weight at the start of the study. But the mice given semaglutide ate less, lost weight and lived longer than mice given placebo injections. Mice treated with semaglutide had an average lifespan of 834 days, about the same as 80 human years, while mice injected with placebos lived a total of 742 days, or about 75 human years.
To test whether it was the weight loss or the drug specifically that was responsible for the benefit, the researchers then reduced the amount of calories given to another group of mice by 25%, roughly the same reduction seen in the mice taking semaglutide.
Like the GLP-1-treated mice, the low-calorie mice lived longer, but there were some differences between the two groups, said UC Berkeley’s Chen, who helped lead the research published in the journal Nature.
For many tissue functions the group examined, including those related to muscle function and mobility, semaglutide-treated mice and calorie-restricted mice performed about the same.
But mice on semaglutide showed some benefits. They worked better to think and finding their way out of a maze, and they were better able to manage their blood sugar than mice on calorie restriction alone.
“It just means it’s more than just calorie restriction and has additional benefits,” Chen said.
Gn Health
