Experts believe that, given the right circumstances, humans can live for an astonishing 115 years, according to….CONTINUE READING
But aging is the No. 1 risk factor for developing diseases and chronic conditions that shorten our lifespan.
Outside of committed lifestyle changes, like avoiding processed foods
and exercising regularly, there are no hacks or magic pills that have been proven to slow the aging process, at least not yet.
There are a few drugs, though, that hold promise for increasing healthy lifespan — including metformin
, a widely used drug that lowers blood sugar in people with type 2 diabetes by improving the body’s use of the hormone insulin.
Researchers around the world are exploring numerous ways to influence the biology of aging, says Jamie Justice, PhD
, researcher and assistant professor of gerontology and geriatric medicine
at Wake Forest School of Medicine in Winston Salem, North Carolina.
“Many different potential interventions have been used on animal models that may increase how long a person or organism lives, called lifespan, and how well they live within those years, called ‘healthspan,’” says Dr. Justice.
Metformin has some qualities that make it stand out among the many medications being investigated, she says.
“While some of these drugs haven’t been researched or used much, or have side effects that are potentially risky, metformin has been used extensively for decades and has a good safety profile. The most common side effects are GI issues such as nausea and diarrhea,” says Justice.
And while other drugs appear to target aging or disease via a single mechanism, metformin appears to positively impact many key pathways, says Justice. “Studies have already shown that metformin can delay aging and improve health in animals, and it may also influence fundamental aging factors that underlie multiple age-related conditions in humans,” she says.
“Metformin’s widespread effects on metabolic and cellular processes, coupled with its well-established safety profile and low cost, make it an ideal candidate drug to extend healthy lifespan in older adults,” says Justice.
Metformin isn’t the only drug with anti-aging promise: Another is rapamycin, a medication used to prevent transplant patients from rejecting donated organs. What sets metformin apart is the fact that it’s a widely available generic medication that is very safe, Justice says.
Right now, most of the evidence about metformin’s impact on longevity comes from research using mice and worms. But the results of these animal studies have been modest, and usually only significant when metformin is started at a young age.
“When researchers have looked at metformin use in mice, it hasn’t had profound effects on how long they live, but research does suggest that taking metformin can extend the healthspan of mice and other organisms,” says Justice. That may be relevant to the research on healthspan and lifespan in humans, she adds.
A meta-analysis published in October 2022 in Aging Cell
, Justice says, found that while metformin wasn’t significantly associated with prolonging lifespan for mice or worms, the mice did show improvements in insulin resistance
and lower levels of oxidative stress, which plays a key role in many chronic diseases. Lower levels of oxidative stress allow cells to repair any damage more effectively.
“Overall, the mice taking metformin seemed healthier. They moved around more and better, their fur looked a little better, and this has been replicated in a few studies,” Justice says.
Research in humans suggests that metformin can impact mortality. A meta-analysis published in 2017
that included 53 different studies concluded that metformin reduces all-cause mortality and diseases of aging, independent of its effect on diabetes.
The analysis found that the use of metformin lowers the risk of cancer, cardiovascular disease, stroke, and death, says Justice.
“The findings on mortality risk are remarkable. Persons with diabetes taking metformin have a lower risk of death than both those with diabetes who are not taking metformin or taking other drugs (like sulphonylureas or insulin) and those without diabetes,” she says.
Diabetes is thought to “accelerate” aging, meaning people with diabetes have a greater risk of getting another chronic disease and greater risk of mortality, says Justice. “That someone taking metformin with diabetes may have a lower risk of death than someone without diabetes is really promising for potential effects on human lifespan. But this needs to be tested definitively in a randomized clinical trial, not just epidemiology or medical records,” she says.
Researchers have known for some time that metformin does more than just help lower blood sugar, says Chris Triggle, PhD , a researcher and professor of pharmacology at Weill Cornell Medicine in Doha, Qatar. “The use of metformin has been shown to reduce the risk of and mortality associated with cardiovascular disease,” he says.
There’s also evidence that it could help with preventing age-related cognitive dysfunction, according to a study published in January 2021 in Aging Cell.
On average, most people lose about six pounds after being on metformin for a year, according to research
. This modest weight loss is “an obvious benefit for many people with type 2 diabetes,” Dr. Triggle says, which “thereby could enhance healthspan and lifespan.”
“But it’s important to note that metformin isn’t really a weight loss drug and most people don’t lose a significant amount of weight from taking it,” says Ashok Shetty, PhD
, a researcher, professor, and associate director at the Institute for Regenerative Medicine at Texas A&M Medicine in Bryan, Texas.
Though losing even a small amount of weight could help improve or even prevent some chronic diseases, researchers are able to use statistical procedures to “tease out” the effects of weight loss, says Justice. “Even after weight is controlled for, research shows that there are still [health] benefits and improvements to taking metformin,” she says.
In the Diabetes Prevention Program study
, participants without diabetes were prescribed exercise, metformin, or placebo to delay diabetes. At the end of the study, metformin appeared to reduce the incidence of diabetes by 30 percent.
“Because of that, metformin is allowed for people who have pre-clinical diabetes,” said Nir Barzilai, MD
, director of the Institute for Aging Research at Albert Einstein College of Medicine in the Bronx, New York, in an interview in Lifespan.io, an organization dedicated to raising funds to research aging and age-related diseases.
Many people who don’t have diabetes still get metformin, Dr. Barzilai pointed out. The problem is the lack of research to back it up. “There are fewer studies about people who are totally normal — lean and healthy,” he said.
Research
has attributed the beneficial effects of metformin to its activation of the enzyme AMPK (AMP-activated protein kinase), which plays many important roles in the regulation of cell metabolism, says Triggle.
AMPK has been referred to as the “fuel gauge of the cell” because research
shows it regulates energy balance and other drivers of aging and lifespan, including metabolism, resistance to stress, cell survival and growth, and autophagy, which is the body’s process of reusing old and damaged cell parts.
In addition to metformin, calorie restriction has been shown to activate AMPK, which has also been associated with enhancing lifespan in numerous experimental studies, says Triggle.
Based on the data that is currently available, it’s very difficult to separate the beneficial effects of metformin in reducing type 2 diabetes from all the other health benefits, including anti-aging, says Triggle.
Triggle was the lead author of a paper published in August 2022 in the journal Metabolism
that synthesized all the existing data on metformin. His team concluded that “the evidence that metformin increases lifespan remains controversial,” and that more data from “appropriately designed clinical trials are required.”
Fundraising for the Targeting Aging with Metformin (TAME) trial
is currently underway. The study aims to find out whether those taking metformin will experience delayed development or progression of age-related chronic diseases such as heart disease, cancer, and dementia. The six-year trial plans to include over 3,000 participants between the ages of 65 and 79 years old.
Researchers are working to develop biomarkers that can quantify the aging process, to show whether metformin is working or not. Without validated biomarkers, it could take decades to run a randomized trial to prove whether a drug safely extended life.
Investigators hope that the people taking metformin will experience a delay in major age-related events and associated beneficial changes in biomarkers of aging.
Because metformin is so inexpensive — just a penny a pill, according to Justice — there isn’t much interest or incentive for drug companies to fund the trial, says Justice, who serves as a member of the trial committee for TAME. It’s also been difficult because the research is “outside the box,” in that it isn’t looking at one specific disease but rather the biological aging process.
Even though metformin’s status as an ultra-cheap generic has made trial fundraising difficult, it could be very beneficial later if the drug is found to have positive effects, says Justice.
“We don’t want to come out with a drug to increase lifespan and healthspan that very few people can afford to take and would widen disparities,” she says. If found to be effective, the low cost and availability of metformin means it could have a population-wide effect, adds Justice.
Is it okay to take metformin to try to live longer even if you don’t have diabetes? That depends on who you talk to, though experts agree that before taking metformin (or any prescription drug, for that matter), you should talk with your doctor.
Unless you are participating in a clinical study, it would not be advisable to use metformin except to treat type 2 diabetes or polycystic ovary syndrome
(PCOS), says Triggle, despite metformin being a generally well-tolerated and safe drug.
“For instance, metformin is not used in patients with severely reduced renal function. It is always appropriate to seek and obtain advice from a health provider before taking any medication,” he says.
Besides, metformin is not an over-the-counter dietary supplement: You need a prescription from a doctor, says Dr. Shetty. “You should only take this under a doctor’s supervision. Lower doses of metformin are quite safe,” he says, although in rare cases, higher doses can contribute to a condition called lactic acidosis. “That’s when lactic acid builds up in the bloodstream, which is a medical emergency and can even be fatal,” he says.
Because metformin’s proposed benefits come from reducing oxidative stress and inflammation, it may not have much benefit for younger people, says Shetty. “Typically, the benefits would be better for middle-aged and older individuals,” he says.
“There are risks that come with taking any drug, and that includes metformin,” says Justice.
Although there are cases of doctors prescribing it off-label, right now most doctors are waiting for more proof — such as the kind TAME could provide — before recommending this to patients, she says….CONTINUE READING