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Reducing insulin signaling in brain helps prolong lifespan (2) |
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11:14, July 22, 2007 |
"To our surprise, all of the engineered mice lived longer," says Akiko Taguchi, PhD, first author of the study. Even more surprising, the mice lacking Irs2 only in the brain lived almost half a year longer than the normal mice -- an 18 percent increase in lifespan -- despite being overweight and having higher blood insulin levels, changes that usually reduce lifespan.
These long-lived mice were more active in old age, retained youthful metabolic cycles (burning sugar by day and fat by night) and retained protective levels of anti-oxidant enzymes such as superoxide dismutase, which protect against oxidative stress, or " biological rusting," in the brain and body.
The mice with normal brain Irs2 levels aged less gracefully -- they lost the metabolic rhythms of youth, became more sedentary, and had reduced anti-oxidant enzymes after meals, leaving them vulnerable to cellular damage. Such damage correlates with a host of age-related diseases such as atherosclerosis, Alzheimer''s disease and cancer, notes White.
White believes the study findings suggest a new approach to preventing diseases that shorten lifespan. "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," he says, "regardless of how much insulin there is in the rest of the body."
Drugs that regulate Irs2 signaling in the brain (but not elsewhere in the body) are one possible preventive strategy, but no such drug has yet been found. Targeted drugs will be important because Irs2 is needed in other tissues, particularly the pancreatic beta cells that produce insulin.
"The easiest way to keep insulin levels low in the brain is old-fashioned diet and exercise," says White.
Eating smaller meals keeps insulin low in the bloodstream, ensuring that less reaches the brain. The new drugs designed to fight insulin resistance and type 2 diabetes might have a similar effect, according to the study published in the July issue of Science.
"This study provides a new explanation of why it''s good to exercise and not eat too much," says White. "It has less to do with how we look, and more to do with a healthy brain, especially in old age."
Source: Xinhua
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