Subtleties of Calorie Restriction and Evolution
My attention was drawn today to a recent open access paper that theorizes on how evolution came to produce the calorie restriction response. Given that calorie restriction notably improves health and longevity, why isn't this beneficial metabolic state switched on all the time?
Stresses like dietary restriction or various toxins increase lifespan in taxa as diverse as yeast, Caenorhabditis elegans, Drosophila and rats, by triggering physiological responses that also tend to delay reproduction. Food odors can reverse the effects of dietary restriction, showing that key mechanisms respond to information, not just resources. Such environmental cues can predict population trends, not just individual prospects for survival and reproduction. When population size is increasing, each offspring produced earlier makes a larger proportional contribution to the gene pool, but the reverse is true when population size is declining....
We conclude that the beneficial effects of stress on longevity (hormesis) in diverse taxa are a side-effect of delaying reproduction in response to environmental cues that population size is likely to decrease. The reversal by food odors of the effects of dietary restriction can be explained as a response to information that population size is less likely to decrease, reducing the chance that delaying reproduction will increase fitness.
The bulk of the paper consists of the mathematical model used to argue this point: evolutionary changes that allow animals to delay reproduction at opportune times will be more successful, as will any adaptation that makes metabolism more likely to identify when those opportune times occur. This seems like a solid theory, given the evidence to hand. Population size and its relationship to the availability of food are very fundamental properties, in play for even the earliest and most primitive species, and similar for many diverse species. Thus we should expect to see what we do see in nature: that the calorie restriction response is a very old aspect of animal metabolism, present in almost all species tested, and governed by very similar genetic mechanisms in species ranging from flies to humans.
In the years ahead, researchers will work out how to permanently and safely turn on the calorie restriction response in humans. This seems like a fairly safe prediction absent a specific timeline, given that the research community for this field is well established and companies continue to raise venture funding to develop methods of metabolic manipulation. They will most likely improve on the natural version to some degree once it is fully understood. The flow of newly discovered longevity mutations in lesser species strongly suggests that all species are far from optimized for longevity, and we should expect to find longevity mutations in humans as well.
That said, a likely 20 year timeline to produce tools that do no more than slow aging will be a grand disappointment for those in middle age today. A 2030 in which we cannot repair aging and reverse its effects to any significant degree would be a death sentence - and a well deserved one, given that we had two decades in which to develop more effective medical technologies than metabolic manipulations to mimic the effects of a natural process.
Ratcliff, W., Hawthorne, P., Travisano, M., & Denison, R. (2009). When Stress Predicts a Shrinking Gene Pool, Trading Early Reproduction for Longevity Can Increase Fitness, Even with Lower Fecundity PLoS ONE, 4 (6) DOI: 10.1371/journal.pone.0006055
Thanks for this well-written summary of our work. If our hypothesis is right, we might want to turn on the calorie restriction or hormesis responses for most of our lives, but maybe not while a couple is trying to have a baby. We don't necessarily expect these responses to shut down reproduction altogether, though, just set insulin etc. at levels that favor longevity but may not be optimal for reproduction.