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Sensible Diet, Exercise and Weight Control Increases Longevity

by VR Sreeraman on Jul 20 2007 4:56 PM

A new research has shown just how a sensible diet, exercise and weight control helps people live a longer life.

A new research has shown just how a sensible diet, exercise and weight control helps people live a longer life.

Researchers from Howard Hughes Medical Institute have found that all these factors increase longevity by reducing signalling through a specific pathway in the brain.

This insulin-like pathway governs growth and metabolic processes in cells throughout the body. The pathway is activated when insulin and insulin-like growth factor-1 switch on proteins inside the cell called insulin receptor substrates (Irs).

Other researchers have already shown that reducing the activity of the pathway in roundworms and fruitflies extends lifespan.

Because reducing insulin-like signalling in the neurons of roundworms and fruitflies extends their lifespan, the researchers decided to examine what would happen when they knocked out one or both copies of the Irs2 gene only in the brains of mice.

Mice lacking one copy of the Irs2 gene in brain cells also showed an 18 percent longer lifespan, and the near complete deletion of brain Irs2 had a similar effect.

Lead author Morris F. White said that the finding had come as a bit of a shock for the researchers.

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“The idea that insulin reduces lifespan is difficult to reconcile with decades of clinical practice and scientific investigation to treat diabetes,” he said.

“In fact, based on our work on one of the insulin receptor substrates, Irs2, in liver and pancreatic beta cells, we thought more Irs2 would be good for you.

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“It reduces the amount of insulin needed in the body to control blood glucose, and it promotes growth, survival and insulin secretion from pancreatic beta cells,” he added.

In earlier work, the researchers had found that knocking out both copies of the Irs2 gene in mice reduces brain growth and produces diabetes due to pancreatic beta cell failure. However, in the new study, when the researchers knocked out only one copy of the gene, they found the mice lived 18 percent longer than normal mice.

“What’s more, the animals lived longer, even though they had characteristics that should shorten their lives—such as being overweight and having higher insulin levels in the blood,” said White.

However, both sets of Irs2 knockout mice exhibited other characteristics that marked them as healthier. They were more active as they aged, and their glucose metabolism resembled that of younger mice.

The researchers also found that after eating, their brains showed higher levels of superoxide dismutase, an antioxidant enzyme that protects cells from damage by highly reactive chemicals called free radicals.

“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,” said White.

“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.”

The study was co-authored by Akiko Taguchi and Lynn Wartschow in White’s laboratory in the Division of Endocrinology at Children’s Hospital Boston and Harvard Medical School.

White speculated that the insulin-like signaling pathway in the brain might promote age-related brain diseases.

“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 said.

“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,” he said.

Source-ANI
SRM/C


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