In:
Aging Cell, Wiley, Vol. 12, No. 6 ( 2013-12), p. 1050-1061
Abstract:
Dietary restriction ( DR ) increases lifespan and attenuates age‐related phenotypes in many organisms; however, the effect of DR on longevity of individuals in genetically heterogeneous populations is not well characterized. Here, we describe a large‐scale effort to define molecular mechanisms that underlie genotype‐specific responses to DR . The effect of DR on lifespan was determined for 166 single gene deletion strains in Saccharomyces cerevisiae . Resulting changes in mean lifespan ranged from a reduction of 79% to an increase of 103%. Vacuolar p H homeostasis, superoxide dismutase activity, and mitochondrial proteostasis were found to be strong determinants of the response to DR . Proteomic analysis of cells deficient in prohibitins revealed induction of a mitochondrial unfolded protein response (mt UPR ), which has not previously been described in yeast. Mitochondrial proteotoxic stress in prohibitin mutants was suppressed by DR via reduced cytoplasmic m RNA translation. A similar relationship between prohibitins, the mt UPR , and longevity was also observed in C aenorhabditis elegans . These observations define conserved molecular processes that underlie genotype‐dependent effects of DR that may be important modulators of DR in higher organisms.
Type of Medium:
Online Resource
ISSN:
1474-9718
,
1474-9726
DOI:
10.1111/acel.2013.12.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2099130-7
SSG:
12
Permalink