Insulin Plays Another Role

Insulin inhibits a gene regulator protein known as FOXO, important in diabetes metabolism, tumor suppression and stem cell maintenance. Studies are now showing reduced insulin leads to greater stress resistance and longer life.

Researchers at the Joslin Diabetes Center have conducted studies that prove insulin plays a role in aging - a finding that could provide a mechanism for gene manipulations and ultimately lead to longer lifespans.

The paper, published in the March 21 issue of Cell, reported that insulin inhibits a master gene regulator protein known as SKN-1, and that increased SKN-1 activity increases lifespan. SKN-1 controls the Phase 2 detoxification pathway, a network of genes that defends cells and tissues against oxidative stress - damage caused by elevated levels of free radicals (byproducts of metabolism) - and various environmental toxins.

"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."

What does this mean for the human body's immune system? SKN-1 may lead to increased resistance to chronic diseases and influence longevity, Blackwell says. The work could be important as it relates to diabetes and vascular and renal complications. But, today's finding may be most important for what it teaches about aging in general, Blackwell says.

"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," he says. "The implications go far beyond diabetes."

It has been known since the 1990s that insulin inhibits a gene regulator protein known as FOXO, important in diabetes metabolism, tumor suppression and stem cell maintenance. FOXO controls a number of genes, including many involved in stress resistance. Studies in C. elegans showed that reduced insulin signaling boosted activity of a FOXO protein known as DAF-16, leading to greater stress resistance and longer life.

SKN-1 is inhibited by insulin signaling and adds to the body of knowledge about insulin and its effects on gene pathways, stress resistance and aging. According to the article, insulin's effect on SKN-1 occurs independently of its effect on DAF-16.

The experiments will have to be repeated in mammals, where insulin has a different effect on tissues. But, according to Blackwell, other findings in the C. elegans model have generally turned out to be applicable to mice and humans.

More information about insulin injection at the Joslin Diabetes Center can be found here.