Rapamycin, Autophagy, and Longevity

An exercise in joining the dots here: TOR, or target of rapamycin, is known to be important in calorie restriction in species ranging from yeast to mammals. We also know that autophagy, the process by which cells recycle damaged components and break down unwanted molecules, appears to be required to gain the benefits of calorie restriction. This paper links autophagy, life span, and rapamycin in yeast, closing the circle: "Rapamycin is an antibiotic that stimulates autophagy in a wide variety of eukaryotes, including the budding yeast Saccharomyces cerevisiae. Low concentrations of rapamycin extend yeast chronological life span (CLS). We have recently shown that autophagy is required for chronological longevity in yeast, which is attributable in part to a role for autophagy in amino acid homeostasis. We report herein that low concentrations of rapamycin stimulate macroautophagy during chronological aging and extend CLS." Many lines of evidence point towards autophagy as an important determinant of longevity. I suspect this is because more autophagy means fewer damaged mitochondria, but that thesis is as yet unsupported by a good weight of evidence.

Link: http://www.ncbi.nlm.nih.gov/pubmed/19458476

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