Molecular mechanisms underlying genotype‐dependent responses to dietary restriction. Issue 6 (11th August 2013)

• Record Type: Journal Article
• Authors: Schleit, Jennifer; Johnson, Simon C.; Bennett, Christopher F.; Simko, Marissa; Trongtham, Natalie; Castanza, Anthony; Hsieh, Edward J.; Moller, Richard M.; Wasko, Brian M.; Delaney, Joe R.; Sutphin, George L.; Carr, Daniel; Murakami, Christopher J.; Tocchi, Autumn; Xian, Bo; Chen, Weiyang; Yu, Tao; Goswami, Sarani; Higgins, Sean; Holmberg, Mollie; Jeong, Ki‐Soo; Kim, Jin R.; Klum, Shannon; Liao, Eric; Lin, Michael S.; Lo, Winston; Miller, Hillary; Olsen, Brady; Peng, Zhao J.; Pollard, Tom; Pradeep, Prarthana; Pruett, Dillon; Rai, Dilreet; Ros, Vanessa; Singh, Minnie; Spector, Benjamin L.; Wende, Helen Vander; An, Elroy H.; Fletcher, Marissa; Jelic, Monika; Rabinovitch, Peter S.; MacCoss, Michael J.; Han, Jing‐Dong J.; Kennedy, Brian K.; Kaeberlein, Matt;
• Is Part Of: Aging cell. Volume 12:Issue 6(2013:Dec.)
• Page Start: 1050
• Page End: 1061
• Publication Date: 2013-08-11
• Subjects: Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.12130
• Languages: English
• ISSNs: 1474-9718

Abstract

<abstract abstract-type="main" id="acel12130-abs-0001"> <title>Summary</title> <p>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 <italic>Saccharomyces cerevisiae</italic>. Resulting changes in mean lifespan ranged from a reduction of 79% to an increase of 103%. Vacuolar pH 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 (mtUPR), which has not previously been described in yeast. Mitochondrial proteotoxic stress in prohibitin mutants was suppressed by DR via reduced cytoplasmic mRNA translation. A similar relationship between prohibitins, the mtUPR, and longevity was also observed in <italic>Caenorhabditis elegans</italic>. These observations define conserved molecular processes that underlie genotype‐dependent effects of DR that may be important modulators of DR in higher organisms.</p> </abstract>