On the Horizon: A Medication to Slow Aging?

Steve Kritchevsky, PhD, has worked long enough to have seen the almost unimaginable become, if not reality, at least possibility.

“I’ve been doing research about aging since about 1995,” says Kritchevsky, professor of internal medicine and translational research in gerontology and geriatric medicine in the Wake Forest School of Medicine’s Department of Internal Medicine. “I’m an epidemiologist; I study people as whole populations, groups of people, in a systematic way.”

Kritchevsky also is co-director of the Sticht Center for Healthy Aging and Alzheimer’s Prevention. He serves as associate dean for research development and associate director and K12 program director of the Clinical and Translational Science Institute.

“My first big project was a large study on mobility disability, following initially well-functioning older adults for 20 years, and I remember asking: ‘Will there ever be a pill to slow aging? Not in my lifetime.’ Yet we are now involved in testing that kind of pill.”

Kritchevsky is leading a pilot study to look at cellular pathways affected by a drug called Metformin to see if those pathways are the same ones that are implicated in the process of aging.

“We have a proposal pending with the National Institute on Aging (NIA) to do a 3,000-person randomized clinical trial of Metformin to see if we can show that it slows the process of aging in older people who do not have diabetes.

“If we can slow the process of aging, we can delay the onset of a number of age-related diseases like cancer and dementia simultaneously. Metformin is a very safe, commonly used drug, and in a variety of animal models, the drug has been shown to extend lifespan and health span.”

“We’ve enrolled more older people at Wake Forest Baptist in trials to improve their health and function than any other single institution in the country and probably the world.”

Steve Kritchevsky, PhD

The proposal is called Targeting Aging with Metformin (TAME), and in addition to Kritchevsky, principal investigators include Wake Forest Baptist’s Mark A. Espeland, PhD, along with professors Nir Barzilai, MD, and Jill Crandall, MD, from the Albert Einstein College of Medicine in New York.

Funding for Innovative Ideas in Aging

“Private philanthropy can be a very significant for a new study such as this one, with a budget of some $10 million a year,” says Kritchevsky. “If we could co-fund it with private funding to make it $5 million, suddenly it becomes a bargain and changes the whole calculus.

“For example, private money could conceivably fund the first year. The current budget, as large as it is, funds only the core of the project. Private funds could also support important add-ons to extend our understanding of how the biology of aging affects health.”

The goal, he explains, is not to cure aging but to explore ways of slowing it.

“Everybody is going to age, but this proposal offers the prospect that we might be able to slow the rate of decline,” says Kritchevsky. “As one of my colleagues, Dr. Barzilai, likes to say, ‘We want everyone to die young at an old age.’

“Imagine if you could slow aging by 5 percent. That’s 5 percent less cancer, 5 percent less heart disease, 5 percent less Alzheimer’s, 5 percent less COPD (Chronic Obstructive Pulmonary Disease), 5 percent less kidney disease. So, the effect on any one disease would not be that impressive, but the effect upon all age-related disease would be an enormous benefit to a population.”

In Kritchevsky’s view, medical science needs to address the number one risk factor for heart disease, cancer, Alzheimer’s, lung disease, kidney disease and pneumonia: Age.

He points out that the nation is not making the type of investment in its health care system to accommodate the excess of diseases that will come with the aging of the population.

“We have to get clever and figure out ways to not have so many of these diseases happen, and that is, in a way, what the Sticht Center is about,” he says. “The nation needs us to figure out how to slow the occurrence of the diseases as well as find better treatments.”

Asked whether Wake Forest Baptist is on the forefront with the TAME study, Kritchevsky says there are researchers at other institutions doing animal studies and a few teams with small pilot studies involving 30 to 40 people each. “But our Metformin study will be a big one, 3,000 people.”

How the TAME Study Emerged as a Research Priority

In 2014, Kritchevsky and Jeff Williamson, MD, program director of the Sticht Center and professor of gerontology and geriatric medicine, participated in a Geroscience Network Grant, funded by the National Institutes of Health (NIH). Gerocience is the interdisciplinary field based on the concept that we can treat and prevent age-related disease by directly targeting the biology of aging.

The network has broad national scope, including the Mayo Clinic, Buck Institute for Research on Aging, Barshop Institute for Longevity and Aging Studies, Albert Einstein College of Medicine, Harvard, Johns Hopkins, Stanford and the universities of Arkansas, Michigan, Minnesota and Washington.

Kritchevsky says discussions with Espeland, Barzilai and Crandall at a geroscience meeting in Spain set the basis for writing a research plan, and that led to creating a team to develop the TAME study.

“Our ability to do human clinical trials focused on aging issues is one of the best in the world,” Kritchevsky says. “We’ve enrolled more older people at Wake Forest Baptist in trials to improve their health and function than any other single institution in the country and probably the world. We’ve enrolled between four or five thousand people in trials over the past 20 years.”

Collaborative Environment with Strong Support

“The reason we were invited into the NIH Geroscience Network is because we had a Claude Pepper Older Americans Independence Center,” says Kritchevsky. There are currently 15 of the these “centers of excellence” in the country funded by the NIH.

“Among Pepper Centers, Wake Forest Baptist is the one with the longest and deepest track record of trials,” Kritchevsky says. “And we are very fortunate to have a notably strong biostatistics group that is famous for its coordination of multicenter trials.”

The Pepper Center is a major research program of the Sticht Center on Healthy Aging and Alzheimer’s Prevention.

“Studying the biology of aging is clearly a profoundly team-based sport—no one brain has the capacity to master all the considerations required to move the field forward. This is the new world of science.

“The world has the tools now to put folks together in a much more distributed network that dims a little of the spotlight from the ‘individual hero’ kind of science.

“There is such a dynamic environment here with the Sticht Center teams. Our innovative collaborative approach within our institution and with others nationally and internationally will allow us to discover and translate findings from lab to treatment more quickly than is possible by individual laboratories or institutions.”