Researchers discover "fountain-of-youth" gene
curious phenomenon that severe dietary restruction can extend the
lifespan of some organisms. The protein is thought to control
whether a mammal stores fat or sheds it, writes Wai Lang
Chu.
The discovery of such a prominent molecular target paves the way for the development of a drug therapy that could determine how much fat the body stores. It not only gives hope to overweight or obese individuals but could also help age-related diseases such as cancer, diabetes and heart disease.
The study, published in the 2 June online issue of Nature, detailed results describing how the Sirt1 mammalian gene promoted fat mobilisation in mice.
The study's authors discovered that fat is released or metabolised by the body rather than stored when the Sirt1 protein senses short-term famine and turns off the receptors that normally keep fat stored in fat cells. Thus fat cells shed their fat.
"If we could make a drug that would bind to Sirt1 and fool the body into thinking that it needed to release that fat, then maybe people could get the benefits of calorie restriction without the side effects," said Leonard Guarente, professor of biology at the Massachusetts Institute of Technology (MIT)in the US.
"For the first time, this study gives us a glimpse of how calorie restriction works at the molecular level. And it will ultimately lead to health benefits in people."
A mammal generally burns the protein and carbohydrates in its food immediately; it stores fat in special cells called white adipose tissue (WAT). When it reduces its caloric intake, the WAT stops storing fat and begins releasing it for metabolism.
The study found that the Sirt1 protein activates a critical component of calorie restriction in mammals; that is, fat mobilisation in white adipocytes. Upon food withdrawal, the Sirt1 protein binds to and represses the genes that are controlled by PPAR-gamma, a lipid regulator, preventing fat from being stored in the body.
"The ability of fat cells to sense famine [or short-term hunger] and release the fat is regulated by this gene."
"We like to think this applies to people as well as mice, but we don't know for sure. If we could make this happen in people, it wouldn't just make them live longer; it might also help prevent diseases of ageing, like cancer, diabetes and heart disease."
Because WAT also makes hormones, especially leptin which controls satiety the scientists have speculated that by putting hormones into the bloodstream, fat cells also tell the body how fast to age.
"Conversely, fewer fat cells tell the body that it's time to hunker down for survival. This means that evolutionarily speaking, fat plays a very important role," Guarente said.
The discovery of this mechanism could provide welcome relief for constant dieters as even the prospect of extending life expectancy is not enough for people to permanently restrict their favourite foods.
Guarente commented: "It's easy to put rodents on a spartan diet. With people it's not so easy, they don't want to diet. It would be like eating every other day and it would create a very lean, cold, unhappy person with no sex drive."
Guarente added that the next step in the process was to determine if an increase in Sirt1 in the body led to a higher rate of metabolism. The intention was to see if this led to an increase in the breakdown of fat and subsequently fat storage.
