Clues to Why Exercise Helps You Live a Longer, Healthier Life

Researchers at the Howard Hughes Medical Institute have uncovered clues to suggest why living a healthier lifestyle will help you live longer. The answer, they say, is less insulin in the brain.

In their experiments, the researchers sought to understand the role of the insulin-like signaling pathway in extending lifespan. This 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).

In earlier work, the researchers had found that knocking out both copies of one of the Irs genes, Irs2, 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.

Because reducing insulin-like signaling 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. “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 Morris F. White, an investigator for HHMI.

However, both sets of Irs2 knockout mice exhibited other characteristics that marked them as healthier, said White. 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.

White and his colleagues are planning their next studies to better understand how healthy aging and lifespan are coordinated by Irs2 signaling pathways in the body and the brain. White speculated that the insulin-like signaling pathway in the brain might promote age-related brain diseases.

Personally, I'll be most interested in seeing how this work meshes with the work being done on Sirtuin. Calorie Restriction methods have not been shown to be effective in humans yet, but there's no reason to think that they won't be. The research on brain insulin, on the other hand, is something that will have to be watched fairly closely. While mice may make an interesting model for early-stage testing, their brains are not that similar to ours and any type of alteration being done on the brain could have effects that would not be obvious in a mouse model.