February 21, 2013

Drugs to slow aging are a matter of when, not if

UW Health Sciences & UW Medicine

A healthy woman, about to turn 94, enjoys a family album. UW researchers are working to reduce the effects of aging and diseases of old age.

Leila Gray

A healthy woman, about to turn 94, enjoys a family album. UW researchers are studying longevity factors to help more people lead long lives and delay diseases of aging.

Evidence is accumulating that not only is it possible to slow down aging, but that by doing so the onset and progression of multiple age-related diseases can be delayed, according to a review by University of Washington scientists in the journal Nature.

“Slowing aging should increase both lifespan and healthspan — the period of life spent in relatively good health, free from chronic disease or disability,” the authors write.

“A shared feature of most medically relevant diseases is that your risk of dying from them increases dramatically as you get older,” said Matt Kaeberlein, senior author of the paper. “Unlike traditional approaches, which tend to focus on a specific disease, targeting the aging process itself has a much greater potential to improve human health.”

UW scientists examine how the inhibition of the protein mTOR, which stands for “mechanistic target of rapamycin,” may modulate aging and age-related disease. The review was written by Simon Johnson, a graduate student in pathology; Peter Rabinovitch, professor of pathology; and Kaeberlein, associate professor of pathology.

Many experts in the biology of aging believe that pharmacological interventions to slow aging are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by mTOR, a protein that controls cell growth.

“Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow aging and reduce age-related pathologies in humans,” said the authors.

The authors compare the effects of mTOR inhibition to the positive effects in rodents of dietary restriction in extending the lifespan and delaying the incidence of age-related decline and disease, including cancer, cognitive decline and neurodegeneration.

“Emerging evidence suggests that, like dietary restriction, mTORC1 inhibition may have similar positive effects on multiple age-related pathologies in rodents and, in some cases, humans,” according to the scientists.

Learn about the work under way in the Kaeberlein lab.

The UW has National Institutes of Health-funded Centers of Excellence in the basic biology of aging (Nathan Shock Center), Alzheimer’s disease (Alzheimer’s Disease Research Center), and Parkinson’s Disease (Morris K. Udall Center), and is working with Kaeberlein to establish the UW Healthy Aging and Longevity (HALO) Research Institute.

“It may sound a bit like science fiction,” said Kaeberlein, “but there is growing confidence in the field that we really can develop drugs that slow human aging and extend the period of healthy life for most people. Imagine what you could do with an extra 10 or 20 years of youthfulness.”

Read more in Nature.