A recent review of two decades of research from the National Institute on Aging (NIA) highlighted 13 anti-aging medications that show promise in preclinical studies for significantly extending lifespan. More than that, they seem to improve the quality of those extra years.
There’s one problem, though. They don’t work for everyone, according to James Nelson, PhD.
“The vast majority of the drugs only work in males,” Nelson said. “There are only three that work in females, and of those three, two of them don't work as well in females.”
Nelson is a professor in the Department of Cellular and Integrative Physiology and the Barshop Institute at The University of Texas Health Science Center at San Antonio, and Barshop is one of three sites in the United States that investigates potential anti-aging interventions for the NIA’s Interventions Testing Program (ITP).
“With all the success of the Interventions Testing Program, we've got one big problem,” Nelson explained. “That is to make these drugs equally effective in females as in males.”
There was one standout intervention in the ITP comprehensive review, on which a recent graduate from Nelson's lab, Nisi Jiang, was the first author. It’s a drug called rapamycin. “It has the biggest impact on longevity in both males and females,” Nelson said. "Rapamycin works probably better in females than in males."
Rapamycin was first discovered in the 1960s, and research has found that it can extend the lifespan of animal models by up to 28%. That’s true even when delivered later in the animal’s life, “Which is the way we'd like it to work, right? We don't want to have to take these drugs throughout our lives to live longer,” Nelson pointed out.
But why does it work as well or better in women than in men? “I don't think I have a really good answer,” Nelson said. He does have a theory, however.
“(Rapamycin) tends to increase insulin resistance a little bit. Insulin resistance is the hallmark of type 2 diabetes. Males are generally a little bit more sensitive to this condition, and it may not be increasing their life span as much, because the drug may be adding to the insulin resistance,” Nelson said, stressing that this was speculation.
It’s no surprise that ITP has uncovered so many anti-aging interventions that work for men, but when used by women, they do nothing or even cause harm, Nelson said. He asked, “Are we surprised that that deleterious side effects incidence is higher in females for most drugs than in males, given the fact that they weren't even studied initially?”
The National Institutes of Health began requiring that National Institutes of Health medical studies include both men and women about 15 years ago, Nelson said, and that’s when he began focusing on sex differences in how medications work. This might also further researchers’ understanding of the biology of aging, more broadly.
“Alzheimer's is not aging. Aging is the biggest risk factor for dementia, but not everybody gets it. Not everybody gets cancer, either. Aging is much more than the increased incidence of dementia, cardiovascular disease, and kidney failure,” Nelson said. Understanding the biological mechanisms that drive aging in both men and women could lead to interventions that not only add years to lives, but also add quality to those years.
“Nobody wants to live longer in a frail state,” Nelson said. “They want to have as much quality of life in their older years as they can get.”
When Nelson considers everything that researchers have learned about aging in the 50 years that he’s been studying it, he doesn’t think it will take 50 more years to answer these questions.
“Back in the day, most biologists said, ‘What are you doing this for? Aging is inevitable, it's too complicated to study,’” Nelson mused, “And here we are, 50 years later, with drugs that show promise for ameliorating age-related dysfunction, frailty, all of the bad things that go with aging. And we're on the cusp of some real progress.”
Science & Medicine is a collaboration between TPR and The University of Texas Health Science Center at San Antonio, about how scientific discovery in San Antonio advances the way medicine is practiced everywhere.
