Dr. Nir Barzilai, the director of the Institute for Aging Research at the Albert Einstein College of Medicine and scientific director at The American Federation for Aging Research (AFAR), predicts it will take a few decades to see impactful gerotherapeutics—drugs that counter the aging process—for the average person. The key is discovering safe and effective drugs that target mechanisms, like inflammation and cellular damage, that lead to aging.
“The evidence that we’re looking for is from clinical trials, not if it cured an animal and not if people who took it told me that they’re doing better,” he told Fortune at the Longevity Investors Conference last month in Gstaad, Switzerland. He says people must be careful not to give into false, baseless promotions of efficacy. “Many people are making decisions based on hope rather than on promise. If you hear something really exciting say, ‘Okay, what’s the data? Did you do a clinical study?’”
A successful gerotherapy, Barzilai says, will do four things:
- Target the hallmarks of aging
- Extend health span by reducing the risk of disease at the end of life
- Be tested for safety and efficacy on hundreds, possibly thousands of people in clinical trials
- Influence all-cause mortality
Geroscience has a long way to go, but there are four FDA-approved drugs that have shown promise to “target the process of aging,” Barzilai says. While not approved as anti-aging treatments, these drugs score the high on his 12-point scale assessing their longevity potential.
“Some of those drugs have been decreasing hospitalization, death, and long COVID, making the point that although some of them are designed for diabetes, they affect immunity,” he said at a lecture at the Longevity Investors Conference. “They affect immunity, and, maybe, they affect the whole body’s ability to be resilient to a severe disease in the end.”
Here are the four:
GLP-1s
Barzilai and other experts have pointed to GLP-1s (Ozempic, Wegovy), the wildly popular class of drugs targeting diabetes and obesity, as potential longevity boosters.
“It was developed for diabetes, and it was shown to actually decrease obesity,” says Barzilai, who adds there is evidence of a reduced risk of heart disease, kidney disease, Parkinson’s, and Alzheimer’s. The drugs scored a 10 out of 12 on the gerotherapeutic scale. “It actually targets the mechanisms of aging.”
Dr. Douglas Vaughan, a professor of medicine at Northwestern University and director of the Potocsnak Longevity Institute, previously told Fortune that extensive research on animals has found calorie restriction as the most effective way to extend life.
GLP-1s suppress appetite and have been shown to improve blood sugar levels for those with type 2 diabetes. They may also play a larger role in chronic disease mitigation and reducing inflammation, although more long-term evidence is needed to also ensure that you can lose weight but not muscle weight.
SGLT2 inhibitors
SGLT2 inhibitors, blood sugar-lowering drugs, are the only drugs on the list scoring a perfect score on Barzilai’s scale. The inhibitors are typically prescribed for those with type 2 diabetes to remove sugar from the kidneys through urine, which lowers blood sugar levels.
The drugs, while used to treat diabetes, show promise in reducing the risk of age-related diseases and kidney disease, by reducing oxidative stress and inflammation, and improving heart health and even cognition. New research also suggests the inhibitors may reduce the risk of dementia in people with type 2 diabetes after longer-term use.
Bisphosphonates
Bisphosphonates, scoring 11 out of 12, treat osteoporosis, which affects 10 million Americans. They are prescribed to those with the condition to reduce the loss of bone density.
“Since their introduction to clinical practice, bisphosphonates have transformed the clinical care of an array of skeletal disorders,” reads one paper published in the Mayo Clinic Proceedings.
Observational studies also suggest the drugs reduce mortality. One analysis found people using bisphosphonates were 15% less likely to die than non-users after a 2.8 year follow up.
Metformin
Metformin, which has been around for 60 years, is the most prescribed type 2 diabetes drug. Studies also show that the drug, scoring an 11 out of 12 as a gerotherapeutic, targets hallmarks of aging like cellular senescence by protecting DNA, decreasing inflammation, and improving insulin sensitivity, according to a paper in the Aging and Disease journal.
However, researchers note that while metformin makes the list as a possible anti-aging drug, the results in non-diabetic patients are not as understood.
More broadly, while research suggests that any of these drugs may target mechanisms of aging, they are not approved for anti-aging alone and eligible candidates are those who typically present with one or more pre-existing conditions.
“Every drug has some contraindication or side effects,” Barzilai says. “You just have to know who’s the right patient.”
People should speak with a provider about their health status, drug interactions, and whether any of these are an appropriate remedy. And still, the main pillars of healthy aging are lifestyle changes, especially for healthy, young people, Barzilai says.
“Not every drug that’s good for old people is good for young people, but the things that are good for young and old are exercise, diet, sleep, and social connectivity,” Barzilai says. “You can always maximize that.”
Still, he says it won’t be lifestyle alone that will be able to dramatically extend human lifespan.
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