Diet and exercise work (here's how)

The July 20, 2007 issue of Science published the results of research conducted at Children’s Hospital in Boston which provides one explanation for the benefits of improved eating habits and exercise on life span.

Working with mice, Akiko Tachi, PhD, Lynn Wartschow, and Morris White of Harvard demonstrate that reducing insulin receptor substrate-2 (Irs-2) signaling increases life span as well as brain levels of superoxide dismutase, a protective antioxidant enzyme.

Acting on the basis of previous research in roundworms and fruit files which found an increase in life span associated with a reduction in insulin signaling, the trio engineered mice to reduce the amount of Irs-2, a protein that carries the insulin signal inside the cell, by half. Because reducing insulin signaling can cause diabetes, the researchers tested their hypothesis that reducing insulin signaling just in the brain, but not the rest of the body, would result in an increase in life span.

They engineered two groups of animals to experience a reduction in Irs-2 in their brains alone, while one group of animals was engineered to have lower Irs-2 in all cells, and another group served as controls.

“To our surprise, all of the engineered mice lived longer,” Dr Taguchi remarked. Despite being overweight and having higher insulin levels, animals with diminished brain insulin signaling experienced an 18 percent increase in lifespan compared to the normal controls. The mice were also more active and retained greater levels of superoxide dismutase in old age.

“The idea that insulin reduces lifespan is difficult to reconcile with decades of clinical practice and scientific investigation to treat diabetes,” Dr White noted. “The engineered mice live longer because the diseases that kill them – cancer, cardiovascular disease and others – are being postponed by reducing insulin-like signaling in the brain regardless of how much insulin there is in the rest of the body. The easiest way to keep insulin levels low in the brain is old-fashioned diet and exercise.”

“Our findings put a mechanism behind what your mother told when you were growing up—eat a good diet and exercise, and it will keep you healthy,” White observed. “Diet, exercise and lower weight keep your peripheral tissues sensitive to insulin. That reduces the amount and duration of insulin secretion needed to keep your glucose under control when you eat. Therefore, the brain is exposed to less insulin. Since insulin turns on Irs2 in the brain, that means lower Irs2 activity, which we’ve linked to longer lifespan in the mouse.”

“We are beginning to appreciate that obesity, insulin resistance, and high blood insulin levels are connected to Alzheimer’s disease, Huntington’s disease, and dementias in general,” he added. “It might be that, in people who are genetically predisposed to these diseases, too much insulin overactivates Irs2 in the brain and accelerates disease progression. Thus, insulin resistance and higher insulin levels might be the environmental influences that promote these diseases.”