By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv

Anti-aging drugs: are they already here?

Are anti-aging drugs already on pharmacy shelves? The question resurfaced after an article in MIT Technology Review. According to the article, Novo Nordisk and Eli Lilly presented “aging clock” data from patients treated with GLP-1 drugs, medications that mimic a natural satiety hormone. On average, their biological age came out about two to three years younger than with placebo.

I have already reviewed the data itself in an earlier article on weight-loss drugs and biological age. This time I want to ask a different question. Is it too early to call them anti-aging drugs? And what does this mean for someone who is healthy and lean?

Anti-aging drugs: what is a geroprotector?

A geroprotector is a drug that slows the aging process itself, not just a single disease. Prof. Steve Horvath of the University of California, Los Angeles, is regarded as the inventor of aging clocks. In his view, a two-year difference is a strong effect. He also believes the data may indicate that GLP-1 drugs are geroprotectors.

The idea did not come out of nowhere. In earlier studies, these drugs protected the heart, improved kidney function and lowered blood pressure. They even reduced the overall risk of death. That is why many researchers are asking whether they act on a mechanism shared by many diseases, in other words on aging itself.

How is biological age measured?

Aging clocks are blood tests that estimate how old the body “really” is. The older epigenetic clocks look at chemical changes that build up on DNA over the years. The newer proteomic clocks, by contrast, measure levels of key proteins in the blood. Some focus on a single organ, such as the heart, kidney or brain. I have discussed this in more depth in my article on the biological clock and 51 longevity studies.

What did Novo Nordisk find with semaglutide?

Novo analyzed blood samples from 10,052 participants in five placebo-controlled trials. The researchers used proteomic clocks at the start of the trials and again later on. The results were released as a preprint, a paper posted online before peer review.

According to the preprint, semaglutide, the active ingredient in Ozempic and Wegovy, reduced biological heart age by about two to four years compared with placebo. The clocks for the kidney, brain, pancreas and lungs also showed reductions of one to four years. However, in a poster the company presented at the American Diabetes Association meeting, the overall whole-body clock did not change.

The heart clock: the most intriguing finding

To my mind, the key finding concerns the heart. In exploratory analyses, the change in biological heart age explained 34% to 49% of the drug’s effect on some of the clinical outcomes. In other words, the clock may reflect a genuine change in heart health, not just a number in a lab. This may be the best hint we have that these are true anti-aging drugs. The researchers themselves stress, however, that the analysis does not prove cause and effect.

What did Lilly find with tirzepatide?

Lilly examined tirzepatide, the active ingredient in Mounjaro and Zepbound, using epigenetic clocks. According to a CNN report, the study included 71 participants over age 50 who received tirzepatide in the SURMOUNT-5 trial. Over the course of the study, 1.38 calendar years passed. The biological clocks, however, advanced by only 0.7 to 1.1 years on average, depending on the type of clock.

To be precise: this study had no untreated control group, and follow-up was short. In addition, Kevin Duffin, Lilly’s vice president for aging research, said that most of the effect probably stems from the drop in blood sugar and weight.

What do the experts say?

Even the researchers involved are cautious. Prof. Vadim Gladyshev of Harvard helped Novo with the measurements. In his words, in an unhealthy population semaglutide behaves like an anti-aging drug. In a healthy population, by contrast, no one knows.

Dr. James Kirkland of Cedars-Sinai Medical Center warned against over-reading the data. He noted that the clocks are useful in studies of groups. In a single individual, however, the result can vary considerably from day to day.

Interestingly, the conference organizer, Alex Zhavoronkov, said he takes “microdoses” of both drugs, even though he is not overweight. That is a personal choice, not a medical recommendation. When he asked the Novo researcher whether a reasonable person should start taking semaglutide, the researcher replied that he is not a doctor and could not answer.

Do lean people need anti-aging drugs?

As of today, the answer is no. Nearly all study participants had overweight, obesity or diabetes. Prof. Horvath himself said he has not yet seen enough evidence of benefit in lean people. So he is not taking the drugs yet, although he has considered it.

What’s more, these drugs have side effects, including loss of muscle mass. In a lean person, and especially at an older age, losing muscle can undermine strength, balance and independence.

The trial that will test anti-aging drugs in healthy people

The first answers may arrive within a year or two. The US research agency ARPA-H (Advanced Research Projects Agency for Health) is providing up to $38 million for a national trial led by UT San Antonio. The trial will include 726 participants in their 60s, who will receive semaglutide, rapamycin, dapagliflozin or placebo.

Unlike the clocks, this trial will measure real-world function: thinking, mobility and the senses. The main measure is intrinsic capacity, a combined measure of physical and mental function. I have written about the evidence for rapamycin in my article on rapamycin and longevity.

Anti-aging drugs: what does this mean for you?

If you have obesity, diabetes or heart disease, the benefit of these drugs in those conditions is well established even without aging clocks. The new data adds another interesting layer. Treatment decisions are always made together with your doctor.

If you are lean and healthy, there is currently no evidence that justifies taking GLP-1 drugs to slow aging. In particular, avoid unapproved products sold online. In the meantime, the proven approaches remain physical activity, strength training, good sleep and a balanced diet.

The bottom line

GLP-1 drugs are currently the closest candidates for the title of anti-aging drugs. The Novo and Lilly clocks point consistently in the same direction, mainly in people with obesity and diabetes. Still, these are biomarkers, not proof of a longer life. Moreover, most of the data came from the companies themselves and has not yet been peer reviewed.

The information in this article is general and does not constitute personal medical advice. Before making any change to your treatment, consult your doctor.

References

Weight-loss drugs show signs of slowing biological aging, say drugmakers

Semaglutide reduces proteomic organ-specific biological age across randomized clinical trials

Semaglutide reduces multi-organ proteomic-based biological age across cohorts

Could GLP-1 drugs be anti-aging medications?

UT San Antonio to lead $38 million national trial testing drugs to extend healthspan

Disclosure: most of the authors of the Novo preprint are company employees and shareholders, and the Lilly data was presented by the company itself.