Discusses how calorie and protein restriction might promote longevity by promoting autophagy.
Famine and Longevity
In the 1930s it was observed that feeding laboratory rats a severely reduced calorie diet otherwise sufficient in other nutrients resulted in life spans of up to twice as long as otherwise expected 10. Similar results have since been produced in a range of other animals from yeast and fruit flies to primates and, to some degree, with just reduced protein11. Though the phenomenon has not yet been demonstrated in humans (they are such difficult lab animals!), many people have independently adopted the practice of calorie restriction in some form as part of research efforts or from their own faith in the subject.
Practitioners of calorie restricted (CR) diets experience improved cholesterol, glucose, and blood pressure profiles and that alone should extend average life-span especially since desirable weight loss usually results. The goal of many in the movement is, however, to extend maximum life-span.
Why should CR extend maximum life-span? Is it simply that metabolism and thus time itself is slowed down? That seems unlikely for a warm-blooded organism whose temperature holds to 98.6°F regardless of diet.
It seems more likely to me that CR promotes autophagy. By living at the edge of starvation, the insulin-signaled autophagy response is likely triggered every time a meal is delayed.
One form of CR involves eating only on alternate days (ADCR). All the benefits of ‘chronic’ CR are also seen with this approach. It has also shown benefit in animal models of HD12, PD13,AD14, diabetes15, cancer16, and asthma17. I will discuss it in more detail in the next chapters.
ADCR seems even more likely than chronic CR to promote autophagy as the trigger is pulled on a regular basis. It is puzzling though why a single day would produce any affect on available calories since the liver maintains a readily-available store of about 500g of glycogen, a starch, representing a reserve of 2000 calories, enough for a whole day. It seems more likely that it is the lack of amino acids from protein that is inducing the autophagy by a pathway independent of the insulin signaling pathway.
Autophagy has been directly implicated in CR at least in roundworms18. Autophagy can be microscopically observed in the living worm when calories are restricted or when induced by a drug. Either CR or the autophagy-inducing drug (rapamycin) extends life span but the two together are not additive. This strongly implies that the life-span extending benefit of CR in worms is from autophagy promotion alone.
A study in fruit flies19has shown that an alternate day protein no-protein diet extends the lifespan as much as a ADCR diet. This and the worm study together (along with many other studies) strongly imply to me that protein restriction promotes autophagy.
This then is the progression for the scientific rationale for the protein cycling diet:
Therefore, if Socrates is a man, protein cycling extends life.