Everyone knows what aging looks like. Wrinkles, high blood pressure, hair loss — those unmistakable signs of deterioration that accumulate as the years pass us by. But a genetics researcher at Brigham and Women’s Hospital would like to take a step back: do we really know what aging is?
“It remains completely unanswered,” said Vadim Gladyshev, a professor of medicine at Brigham and Women’s Hospital. Despite a flood of antiaging research and advances in extending the life span of some laboratory animals, Gladyshev thinks that broader questions about aging remain unanswered. Researchers have delved deeply into specific and powerful cellular processes that appear to be involved in aging without fully understanding how or if they’re connected to the phenomenon of a young organism becoming an old one.
For example, accumulating damage in cells is commonly thought to result in aging, but Gladyshev doesn’t think even that assumption has been carefully tested. He pointed to the trash can in his fourth-floor office and noted that it could fill up with garbage, but that would not mean that his ability to do work would change.
So Gladyshev came up with a new way to probe aging. Instead of looking for clues by studying longer- and shorter-lived individuals of a particular species, why not look at the diversity of an entire class of organisms? Evolution, he notes, has been better at tweaking the life spans of organisms than any laboratory researchers have been: among mammals, there can be a gigantic variation in life span between different species. What, he wonders, are the genetic differences that mean an elephant can live for 70 years, a squirrel can reach its 20th birthday, but a shrew may expire after just one?
This fall, Gladyshev received a federal grant aimed at supporting high-reward, high-risk research that will extend the search for mechanisms of aging, by asking questions from an evolutionary perspective. Gladyshev will collect samples from 50 mammals whose natural lives vary, from the longest- to the shortest-lived.
It's research that takes Gladyshev into unusual partnerships for biomedical scientists, who are more likely to write e-mails to one another requesting cells than to call up wildlife biologists in other countries. Recently, for example, he enlisted a team of Russian scientists to gather samples from the Brandt’s bat, a 5-gram mammal that has been documented to live 41 years.
The sample collection mission involved a long drive into remote country through subzero temperatures, followed by a 10-mile cross-country ski trip to the cave where the bats live. Ropes were used to lower scientists into a dark, cold cave where they could collect the bats, identify them, and use liquid nitrogen to preserve the samples. In a paper published in the journal Nature Communications this summer, Gladyshev and the Russian researchers described the bat’s genome, and compared it with other mammals. They identified genetic alterations in genes that may be involved in life span, and Gladyshev hopes to examine those genes in greater detail to see whether they play a role in the tiny creature’s remarkable longevity.
By eventually comparing gene activity in many mammals, he hopes to identify genes and control mechanisms that might control aging — and provide potent targets for researchers hoping to develop therapies that could extend life or combat diseases of aging.
And he’s still looking for partners who could provide elephant and whale samples.