Speculative Calorie Restriction Research in Nematodes

Calorie restriction extends life and slows progression of near all measurable aspects of aging in near all species tested to date. The underlying mechanisms are inherited from the deep evolutionary past and are therefore very similar even between yeast, nematode worms, mice, and humans. One of the most interesting things about the calorie restriction response is that researchers can study nematodes and then have a fair expectation that much of what is learned will have some relevance to human biochemistry.

There are of course limits to the degree to which one can take findings in lower animals and expect them to hold up in humans. Nematodes for example have a dauer stage in growth that they enter and exit based on environmental circumstances: it is a form of stasis in which they can survive for great lengths of time in comparison to their normal life span. Effects that involve the dauer stage are unlikely to be of any great relevance to higher species that do not have this capability, however. So I think it is very speculative that this research will have any great application to human metabolism, for all that it is well crafted:

Organisms in the wild often face long periods in which food is scarce. This may occur due to seasonal effects, loss of territory, or changes in predator-to-prey ratio. During periods of scarcity, organisms undergo adaptations to conserve resources and prolong survival. When nutrient deprivation occurs during development, physical growth and maturation to adulthood is delayed. These effects are also observed in malnourished individuals, who are smaller and reach puberty at later ages.

Developmental arrest in response to nutrient scarcity requires a means of sensing changing nutrient conditions and coordinating an organism-wide response. How this occurs is not well understood. We assessed the developmental response to nutrient withdrawal in the nematode worm Caenorhabditis elegans. By removing food in the late larval stages, a period of extensive tissue formation, we have uncovered previously unknown checkpoints that occur at precise times in development. Development progresses from one checkpoint to the next. At each checkpoint, nutritional conditions determine whether animals remain arrested or continue development to the next checkpoint.

Diverse tissues and cellular processes arrest at the checkpoints. Insulin-like signaling and steroid hormone signaling regulate tissue arrest following nutrient withdrawal. These pathways are conserved in mammals and are linked to growth processes and diseases. Given that the pathways that respond to nutrition are conserved in animals, it is possible that similar checkpoints may also be important in human development.

Link: http://dx.doi.org/10.1371/journal.pgen.1004426


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