Linking Aging, Telomere Length, and Calorie Restriction

Researchers establish a link between calorie restriction, aging, and telomere length in yeast, but one which poses more questions than it answers: "Dietary restriction promotes longevity in many species, ranging from yeast to primates, and delays aging-related pathologies including cancer in rodent models. There is considerable interest in understanding how nutrient limitation mediates these beneficial effects. Much of what we have learned about the genetics of aging comes from studying isogenic model organisms, where the effects of single gene changes can be examined independently of other genetic alterations. In order to explore a broader spectrum of genetic variation and to gain insight into aging-related phenotypes as polygenic traits, we analyzed the chronological lifespan of 122 S. cerevisiae strains derived from a cross between laboratory and vineyard yeast strains. The major genetic locus controlling chronological lifespan was found to be identical to a previously mapped locus that controls telomere length. Identification of the responsible polymorphism in BUL2, a gene involved in controlling amino acid permeases, allowed us to establish a previously unrecognized link among cellular amino acid intake, chronological aging, and telomere maintenance. While human epidemiological studies have linked shortened telomeres with increased mortality, it is unclear how these processes are connected. Our results suggest that, in yeast, reduced amino acid uptake and consequent reduced nutrient signaling extend chronological lifespan but reduce telomere length."

Link: http://dx.doi.org/10.1371/journal.pgen.1002250

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