Cutting back on calories and dropping a few pounds would help most of us feel better. But researchers have known for nearly century that drastic caloric restriction can actually delay the aging process and lead to a longer, stronger old age. While the effect of dietary restriction has been studied and confirmed in species ranging from the simple c. elegans roundworm to much more complex animal models, the precise molecular mechanisms that govern it have largely eluded identification.
Now, a scientist at the MDI Biological Laboratory in Bar Harbor has identified an important genetic response that underlies the process. The discovery, published recently in the peer-reviewed journal Aging Cell, raises the possibility of developing therapeutic drugs that stave off aging and prolong the “health span” in humans — without the unpleasant and potentially risky constraints of severe dietary restriction.
“Someday, it could be the norm for 40- or 50-year-olds to start on a course of therapeutics that would increase their health span,” said Aric Rogers, Ph.D., who has been investigating the mechanisms of aging at MDIBL for about four years.
“The goal is not to live super-long,” he said, because few people would want to prolong a life of illness and frailty. Instead, Rogers is excited by the possibility that our natural lifespans could be spent in robust good health, with only a short period of failing energy at the end.
Rogers said in a recent interview that early studies, undertaken decades ago, severely restricted the caloric intake of laboratory rats and mice while providing adequate amounts of vitamins, minerals and other micronutrients. Those animals “grew more slowly but lived 30 to 50 percent longer,” Rogers said. But lacking a sophisticated understanding of biological structures and mechanisms, there was no framework to understand how dietary restriction might affect humans, he said.
Since then, advances in genetics and molecular science have determined that dietary restriction inhibits the production of specific cellular proteins and increases the production of others. Still, no one has pinpointed specifically how or why.
But Rogers’ lab has taken a big step forward. His recent study identified one mechanism that underlies the phenomenon in the lowly c. elegans roundworm, which shares more than 50 percent of the human genome.
A severe lack of of caloric energy activates a specific “survival gene” that restricts proteins associated with growth and reproduction and ramps up production of proteins associated with cell balance, maintenance and health, he said.
This means that cells are quicker to destroy damaged, misshapen or toxic proteins, such as those associated with Parkinson’s disease, Alzheimer’s disease and other age-related conditions. Knowing that, this increased efficiency also could be triggered by a targeted therapeutic drug that would “gently kick our survival and maintenance genes into action,” Rogers said.
Rogers and other researchers continue to study the effects of dietary restriction and how to stimulate the protective response, but not everyone is waiting to find out the results.
“A lot of people are not waiting for a drug to be developed or for the final scientific word,” Rogers said. Armed with the existing knowledge, he said many people are already experimenting with cutting back their dietary intake. Some eat only every other day or fast one day per week or on weekends. Some consciously reduce their dietary proteins. Individual steps like this may or may not increase the efficiency of cellular maintenance and delay the effects of aging, Rogers said, but people must pay careful attention to maintaining recommended levels of essential nutrients to avoid becoming ill or malnourished.
In the meanwhile, he said, scientists already are studying existing drugs to see if they can be used to activate the mechanism that occurs, naturally, in response to a more stringent diet than most of us are willing to undertake.