Insulin Research May Lead to Longer, Healthier Life

Insulin can affect aging and lifespan, a previously unknown outcome which could provide a means of gene manipulation capable of lengthening lives and making people healthier.

In a recent paper, researchers from the Joslin Diabetes Center note that Insulin inhibits a master gene regulator protein called SKN-1, whose activity increases lifespan. SKN-1 also controls what is called the Phase 2 detoxification pathway, a network of genes that defends cells and tissue against oxidative stress—damage caused by elevated levels of free radicals (byproducts of metabolism)—and various environmental toxins. This new research result was validated in experiments on the digestive system of C.elegans, a microscopic worm often used as a model organism.

"We’ve found something new that insulin does and it has to be considered when we think about how insulin is affecting our cells and bodies," said Dr. T. Keith Blackwell, senior investigator at Joslin and author of the paper. "This has implications for basic biology since under some circumstances insulin may reduce defense against the damaging effects of oxidative stress more than we realize."

Enhancing the activity of SKN-1 may lead to increased resistance to chronic diseases and influence longevity, said Dr. Keith, and the work could be important as it relates to diabetes and the many problems associated with the disease, particularly vascular and renal complications.

"The major implication is that we have found something new that affects lifespan and aging, and an important new effect that insulin and/or a related hormone called insulin-like growth factor-1 may have in some tissues," said Blackwell. "The implications go far beyond diabetes."

A gene regulator protein called FOXO is important in diabetes metabolism, tumor suppression and stem cell maintenance, a fact known since the 1990’s. FOXO controls a number of genes involved in stress resistance, and studies in C.elegans demonstrated that diminished insulin signaling increased activity of a FOXO protein called DAF-16, leading to greater stress resistance and longer life.

The Joselin research adds to knowledge about insulin and its effects on gene pathways, while putting SKN-1 next to FOXO as a second master gene regulator that is inhibited by insulin signaling. According to the paper, insulin’s effect on SKN-1 occurs independently of its effect on DAF-16.

The paper was published in the March 21, 2008 issue of Cell.

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