Study finds insulin inhibits master gene regulator that increases lifespan

Washington, Mar 21 : Joslin Diabetes Center researchers have identified a previously unknown effect of insulin that has a major role to play in aging and longevity.

The study, led by Dr. T. Keith Blackwell, an Associate Professor of Pathology at Harvard Medical School and faculty member at the Harvard Stem Cell Institute, has cited that insulin inhibits a master gene regulator protein known as SKN-1, and that increased SKN-1 activity increases lifespan.

This finding may further provide a mechanism for gene manipulations that could help people live longer and healthier lives.

SKN-1 controls the Phase 2 detoxification pathway, which is a network of genes protecting cells and tissue against oxidative stress, damage caused by elevated levels of free radicals (byproducts of metabolism), and various environmental toxins.

The researchers displayed the new finding 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. 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," said Blackwell.

He also said that the aim is to refine SKN-1 activity, which may lead to increased resistance to chronic diseases and influence longevity. The study holds credibility as it is concerned with diabetes and various problems linked with the disease, particularly vascular and renal complications.

However, he said that the recent finding may be most important for what it teaches about aging in general.

"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. The implications go far beyond diabetes," said Blackwell.

Since long, insulin is known to inhibit a gene regulator protein called FOXO, which is vital to 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 signalling heightened activity of a FOXO protein known as DAF-16, leading to greater stress resistance and longer life.

However, according to the new study, SKN-1 is placed alongside FOXO as a second master gene regulator that is inhibited by insulin signalling and tells about insulin and its effects on gene pathways, stress resistance and aging. Also, the study says that insulin's effect on SKN-1 occurs independently of its effect on DAF-16.

"You can manipulate the expression of SKN-1 and the worms live longer," said Blackwell.

Though the experiments will have to be repeated in mammals, where insulin and insulin-like growth factor-1 have a complex array of effects in different tissues. But, according to Blackwell, other findings in the C. elegans model are generally applicable to mice and humans.

The study is published in the latest issue of Cell.

ANI