One of the more interesting frontiers in research aimed at slowing aging is the search for methods that complement calorie restriction rather simply recapturing a part of its benefits to health and longevity. To date, there have not been much in the way of results on this count, but I think that this will change: the number of ways to extend life in laboratory animals is expanding rapidly, as is the pool of funding for the field.
You might recall last year's research demonstrating rapamycin to extend life in mice, and to a great enough degree to be a contender for the Mprize for longevity science.
Compared with the non-drug-taking group, the lifespans of the mice given rapamycin increased by up to 14%, even though they were middle-aged when treatment began. Their life expectancy at 20 months shot up by 28% for the males and 38% for the females.
On this topic, my attention was caught today by research into rapamycin-related biochemistry in flies:
The target of rapamycin (TOR) pathway is a major nutrient-sensing pathway that, when genetically downregulated, increases life span in evolutionarily diverse organisms including mammals. The central component of this pathway, TOR kinase, is the target of the inhibitory drug rapamycin, a highly specific and well-described drug approved for human use. We show here that feeding rapamycin to adult Drosophila produces the life span extension seen in some TOR mutants. Increase in life span by rapamycin was associated with increased resistance to both starvation and paraquat. Analysis of the underlying mechanisms revealed that rapamycin increased longevity specifically through the TORC1 branch of the TOR pathway, through alterations to both autophagy and translation.
Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms.
That last part is the interesting point, for me at least. Based on the behavior of rapamycin and calorie restriction tested separately in flies and mice, it would be consistent for rapamycin to further extend the life span of calorie restricted mice - and hence other mammals too. Which in turn means, as the authors point out above, that there exist other accessible mechanisms of metabolic determination of longevity that are not triggered by calorie restriction.
If forced to guess - which, frankly is a fool's game in anything to do with biology - I'd say that these additional mechanisms are involved in genetic translation rather than autophagy. We already know that autophagy and calorie restriction are strongly linked; there is a plausible argument that calorie restriction exerts its effects largely through increased autophagy and the consequences thereof.
Autophagy is, broadly speaking, the process by which your cells recycle damaged components. ... more autophagy appears to be a good thing. You don't want damaged organelles running wild in your cells; one only has to look at the mitochondrial free radical theory of aging to see where that can lead - a trick of biochemistry prevents mitochondria from being recycled, and ever more damaged cells spew toxins into your body, causing the degenerations of aging that follow.
Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, & Partridge L (2010). Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell metabolism, 11 (1), 35-46 PMID: 20074526