The biochemistry surrounding insulin and insulin signaling is very well studied in the context of aging. A number of ways to slow aging in laboratory species involve directly manipulating these signaling pathways. Calorie restriction, like a number of other methods of slowing aging, improves insulin sensitivity, and the consensus in the research community has been that some fraction of the benefits to health and longevity that result from a restricted calorie intake are derived from this change to insulin metabolism. Today's open access paper provides evidence to suggest, surprisingly, that this is not in fact the case. It is possible to block this part of the calorie restriction response, and the effect on health and longevity is much the same.

What, then, are the mechanisms by which calorie restriction produces extension of life span in short-lived species? The evidence to date points towards upregulation of autophagy. Autophagy is the name given to a collection of processes responsible for recycling damaged or unwanted cellular structures and protein machinery. Many methods of slowing aging in laboratory species prominently feature increased autophagy; in principle, cells that are better maintained will experience fewer issues and this results in better tissue function and a slower decline into age-related degeneration. Certainly, it is the case that when autophagy is disabled, then calorie restriction no longer acts to extend life.

Calorie-Restriction-Induced Insulin Sensitivity Is Mediated by Adipose mTORC2 and Not Required for Lifespan Extension