BWH Clinical & Research News

Gladyshev’s Quest to Understand Aging

Vadim Gladyshev

Vadim Gladyshev, PhD, a principal investigator in the Division of Genetics at BWH, cites his high school chemistry teacher as one of his inspirations for studying science. He recalls the days after class when the chemistry club would meet to perform experiments, solve problems and read scientific magazines. These experiences made his decision to become a scientist a simple one.

Although Gladyshev went on to study chemistry at Moscow State University in Russia, his interests grew more diverse over the course of his career, branching into biochemistry, biology and genomics. After graduating with a degree in biochemistry, Gladyshev worked at the National Institutes of Health for five years before earning a faculty position at the University of Nebraska in Lincoln, where he developed a research program in selenium and redox biology. After working in Nebraska for 11 years, Gladyshev wanted to work in a new and collaborative environment, so in 2009 he moved his lab to BWH.

Now his attention is directed at one subject in particular: aging.

Gladyshev’s lab investigates the molecular basis for natural changes in longevity and the biological mechanisms involved in aging. “Ultimately, we would like to find treatments or some other approaches which would help extend life span and diminish the consequences of age-related diseases,” said Gladyshev. “Yes, we already live long—the human life span is actually exceptionally long for our body size, but there is no reason why we cannot live even longer.”

While the mechanisms of aging and the process of life span control may seem to be highly related topics, Gladyshev maintains that they are different areas of study. To explain the difference, he uses the analogy of a river flowing from a mountain to the ocean, where a lifespan would be equivalent to the time it takes for the water to flow from the source to the beach. According to Gladyshev, we can change the route of the river to make the journey longer, just like we can work to extend the lifespan of humans. However, we cannot change the fact that the river flows, just like we cannot change the fact that the aging process occurs.

Gladyshev is particularly interested in developing treatments to prolong life span. To do this, his research team uses multiple approaches. One methodology involves studying the genes of animals that have evolved drastically different life spans, such as the Brandt’s bat and naked mole rat. The Brandt’s bat is a species commonly found in Europe and Asia, and while it is one of the smallest mammals, it often lives for more than 40 years. The naked mole rat is a burrowing animal commonly found in East Africa, normally characterized by its small eyes, short legs, hairless body and large front teeth. This animal can live up to 31 years, ten times longer than the typical life span of a mouse of the same size. “It’s not like evolution wanted the naked mole rat to live longer, but in that particular environmental niche, the organism happened to live longer,” said Gladyshev. “Its life span is defined by its genome, and we are trying to uncover what those changes in the naked mole rat genome may be.”

In addition to the evolutionary study of long-lived animals, Gladyshev’s lab applies “-omics” approaches across large groups of mammals as well as across different cell types, comparing cells like neurons that are fully differentiated and can live for a hundred years, to monocytes in the blood that typically only live for a few days. These analyses identify genes and pathways that are associated with changes in life span. Gladyshev and his lab then seek pharmacological and genetic treatments that can induce these genes and pathways, thereby extending life span. They also analyze treatments that are already known to induce longevity. By looking at common and distinct features in these treatments, Gladyshev is hoping to understand the different ways the aging process can be delayed.

While the aging process in humans cannot be stopped, Gladyshev and his team are working to manipulate it with the hope of also delaying, all at once, the incidence of age-related diseases like cancer, heart disease, diabetes and Alzheimer’s disease. According to the American Cancer Society, 86 percent of all cancers are diagnosed in people 50 years of age or older, and research from the National Institutes of Health indicates that risks for developing heart disease follow a similar pattern. According to the National Institute on Aging, the prevalence of Alzheimer’s disease doubles nearly every five years in adults 65 or older. “Aging is the main risk factor for these diseases, making it a prime target for biomedical research, and it is also an incredibly interesting and challenging question from a scientist’s perspective,” Gladyshev said.

Although Gladyshev’s goal is to better understand the aging process and ultimately extend the human life span, he maintains that the most rewarding aspect of his work is the feeling of discovery and involvement in the scientific process. As a scientist, Gladyshev says he is mainly driven by curiosity and a desire to answer big questions about interesting topics, like aging.

“I think I’m in the best profession because we do what we really like,” Gladyshev said. “It’s both a profession and a hobby, and fortunately there are yet many interesting questions to answer.”