Calorie restriction lengthens lifespan, in part, due to mitochondrial metabolism reorganization through [sirtuin 1-regulated] mitochondrial biogenesis. This reduces radical oxygen species levels that cause macromolecule damage, a major contributor to aging.
Little is known about these processes in stem cells, whose longevity is implicated in human aging. Recent work indicates that sirtuin 1 influences growth-factor responses and maintenance of stem cells. Sirtuin 1 is required for calorie restriction-induced lifespan extension in mice, and calorie restriction upregulates sirtuin 1 in humans. Sirtuin 1 also appears to influence lineage/cell-fate decisions of stem cells via redox status.
I notice that sirtuins are also theorized to link processes important to cancer suppression and processes important to insulin metabolism (one of the important metabolic determinants of life span), which is why rate of aging and cancer risk seem balanced against one another in most organisms:
Recent evidence suggests that the sirtuin family of proteins act as central mediators of this molecular crosstalk. The coordination of DNA repair with overall energy balance may be essential for reducing the risk of developing cancer as well as for determining the rate at which we age.
On the way past Ouroboros, I notice that Chris Patil has posted on sirtuins as well. So sirtuins it is today:
As theories reach maturity (and middle age), they are naturally subject to challenge, and the sirtuin story is no exception. The role of sirtuins in [calorie restriction] has been challenged, sometimes by the very founders of the field. The mechanism(s) of action of resveratrol are also under close scrutiny. Even some of the most famous studies of sirtuins - specifically, regarding effects on median lifespan and exercise tolerance - used animals eating such horrifyingly fatty diets or ingesting such gigantic doses of resveratrol that their relevance to humans must be questioned.
It’s therefore high time that we turned a skeptical eye to the sirtuin story.
It's all a good illustration that researchers still have a way to go to untangle the workings of calorie restriction - you'll find gaps and contradictions when you look closely at the brace of theories, experiments and knowledge produced to date. I'm still betting on four to five years for a solid picture of this biochemistry of enhanced health and longevity, based on the current rate of progress.