The traditional prescriptions for a healthy life Sensible diet, exercise and control, extend life by reducing signaling through a specific pathway in the brain, according to Howard Hughes Medical Institute researchers who discovered the connection while studying long-lived mice.
They said their findings underscore the importance of maintaining a healthy lifestyle and may also offer promising research directions for understanding and treating diabetes and Alzheimer’s disease.
Howard Hughes Medical Institute investigator Morris F. White and his colleagues published their findings in the July 20, 2007, issue of the journal Science. Akiko Taguchi and Lynn Wartschow in White’s laboratory in the Division of Endocrinology at Childrens Hospital Boston and Harvard Medical School were co-authors of the research article.
The Role of Insulin Signaling
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).
Other researchers had shown that reducing the activity of the pathway in roundworms and fruitflies extends lifespan. Despite those tantalizing clues, White said, The idea that insulin reduces lifespan is difficult to reconcile with decades of clinical practice and scientific investigation to treat diabetes.
In fact, based on our work on one of the insulin receptor substrates, Irs2, in liver and pancreatic beta cells, we thought more Irs2 would be good for you, said White. It reduces the amount of insulin needed in the body to control blood glucose, and it promotes growth, survival and insulin secretion from pancreatic beta cells.
In earlier work, the researchers had found that knocking out both copies of the Irs2 gene 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.