Research on aging: the 'wild west of science'

High-profile papers by Marc Tatar and John Sedivy on the biology of aging help raise awareness of Brown's excellence in the field.

by Wendy Y. Lawton

Despite light-speed advances in science, basic questions remain about aging. Why do we slow down, sicken and die? What roles do diet, stress and genes play in the picture? And which parts of our bodies, from organ systems to mere molecules, control how long we live?

These questions have sparked an explosion in aging research, arguably the hottest topic in biology today. The Holy Grail: how to keep single cells and entire organisms - humans included - healthier, longer.

Evidence of the boom is everywhere.

Research funding for the Biology of Aging Program at the National Institutes of Health has jumped from $54 million to $141 million in the last decade. During that same period, NIH grant requests to study the genetic and molecular basis of longevity rose from 19 to 70. Meanwhile, papers on the topic increasingly run in top-shelf, mainstream journals such as Science and Nature. The biology of aging has even spawned a new journal, Aging Cell, as well as its own Web sites.

The University of Michigan, the University of Washington and the University of Texas have powerhouse programs in the field, according to Huber Warner, associate director for the Biology of Aging Program at the National Institute on Aging.

But Brown University, Warner said, sits squarely on the map.

"Brown is small but excellent in this area," Warner said. "It can't compete in terms of lab size or funding, but the quality of research is high. You've got a couple of nationally-known, highly-regarded scientists there.

These scientists are Marc Tatar and John Sedivy. Both professors - Sedivy in medical science, Tatar in ecology and evolutionary biology - have published high-profile papers in the past five weeks.

Sedivy's work, appearing in the May 21 issue of Molecular Cell, showed that at least two molecular mechanisms trigger senescence, a cellular process associated with aging and a key to understanding cancer and age-related illnesses. The findings will be of interest to scientists developing new-generation drugs that target cancer on the molecular level.

Tatar's research ran in the June 3 issue of Nature. Tatar and his team found that the life expectancy of fruit flies increases an average of 50 percent when signals within cells of fat tissue are blocked or altered. Results of the study suggest that reduced levels of insulin in one tissue regulates insulin throughout the body to slow aging - a finding that brings science one step closer to cracking the longevity code.

Although their research focus is different - Sedivy studies single cell division and death; Tatar investigates how hormones affect whole organism aging - the pair frequently cross paths. For four years, they taught genetics together. And for seven, they've helped organize an annual Brown academic conference on the biology of aging.

Both men were attracted to the field for one reason: Aging poses essential, enthralling questions. Sedivy is fascinated by the notion of a biological clock and how to manipulate it. Tatar simply wants to know why humans age.

"Age is a loss of function," Tatar explained. "It's a degenerative process. But we don't know the mechanisms that lead to degeneration."

Despite so many unanswered questions, scientists have staked out some solid ground, according to George Martin, scientific director for the American Federation for Aging Research.

As organisms age, metabolic machinery slows, cognitive function declines, and motor control and balance suffer, Martin said. Research has also shown that aging affects all systems, from the central nervous system to the reproductive system. "Things all start going downhill together," he said. "In mice, it happens in five or six months. In humans, typically, in the fourth decade."

Recently, scientists discovered that slowing insulin-like signaling in worms, flies and mice enhances longevity - the first evidence of an aging mechanism shared by different species.

Several factors gave rise to this knowledge boom. Technology - particularly tools that identify and alter individual genes - has been key.

"Aging research is still the wild west of science," Tatar said. "It's only been in the last 12 to 15 years has it become possible to study it at a molecular level. It's as if we're standing at this sea and we finally have a boat to explore it on. If we can make it float, really make this stuff work, I'll live for a long time myself."