Caloric Restriction And Aging

Underground Fat Loss Manual

Best Weight Loss Programs That Work

Get Instant Access

Caloric restriction (30-40% reduction in total caloric intake without malnutrition) has been recognized for over 60 years (33) as a means to extend the life span in many species, including rodents and probably primates. Similar to the dauer pathway in C. elegans, caloric restriction increases stress resistance and postpones reproduction. Certain mutations in C. elegans affect the ability to eat ("eat" mutants) and the rate of living, including feeding ("clk" mutants). Genetic epistasis experiments indicate that mutations in eat and clk affect the same pathway (reviewed in Ref. 34). In contrast, the daf pathway is independent, because daf-2 clk-1 double mutants live longer than either single mutant. Which of these mutants most closely resembles caloric restriction (CR) is not clear. The mechanism of CR has not been elucidated, but one hypothesis is that is that it slows the production of toxic ROS, and thus decreases the accumulation of oxidative damage. Interestingly, some important connections have been recently described among diet, clk-1 mutants, and daf mutants. Coenzyme Q is an essential cofactor that acts as a carrier of electrons and protons across the inner mitochondrial membrane, maintaining the proton gradient driving ATP synthesis. Larsen and Clarke (35) have shown that withdrawl of coenzyme Q from the diet extends the life span of wild-type or daf or clk-1 mutant C. elegans.

CR also draws a connection between reproduction and aging. In the absence of reproduction, suppressed either by adverse environmental conditions, or by ablation of germ cells in C. elegans or Drosophila, the life span in prolonged. This occurs presumably in an attempt to delay reproduction until a more favorable time in order to ensure the survival of the species. Thus, we begin to see stretching the life span as another potential mechanism of evolution, and successful aging as possibly subject to evolutionary pressure rather than being beyond its effects. It is obvious from an examination of the remarkable ranges of the life span among related species, that given certain appropriate ecological niches, species can indeed evolve new life history strategies, including decreases in rates of aging and substantial enhancements of longevities. Field studies of sibling species have provided strong support for this statement (36). The genomic remodeling that accompanies such enhanced life spans can be presumed to include various "longevity assurance genes" (37). These observations do not obviate significant roles for evolutionary theories of aging that are concerned with different classes of gene action, such as Medawar's suggestion of the accumulation of constitutional mutations that escape the force of natural selection (or the concept of antagonistic pleiotrophy) (38) in which certain alleles are beneficial early in life, prior to reproduction, at the expense of deleterious effects of these same alleles late in life. A mix of these and other classes of gene action (39) will evolve to optimize reproductive fitness in given ecological niches. Given high environmental hazard functions, species will evolve with comparatively short life spans and many offspring (fish, mice). Low hazard environments will favor the emergence of species with comparatively long life spans and few offspring (elephants, humans). The existence of a latent mechanism for increasing the life span may be more prominent in short-lived species. Hypothetically, some of these mechanisms may already have been constitutively activated or maximally exploited during evolution from a short-lived ancestor to their present day long-lived descendents.

Was this article helpful?

0 0
Weight Loss New Years Resolution Success

Weight Loss New Years Resolution Success

Sure you haven’t tried this program before but you no doubt aren’t a stranger to the dieting merry go-round that has been plaguing your life up to this point.

Get My Free Ebook

Post a comment