Molecular mechanisms underlying genotype‐dependent responses to dietary restriction

Aging Cell

Jennifer Schleit⁴  Simon C. Johnson⁴  Christopher F. Bennett⁴  Marissa Simko⁴  Natalie Trongtham⁴  Anthony Castanza⁴  Edward J. Hsieh³  Richard M. Moller⁴  Brian M. Wasko⁴  Joe R. Delaney⁴  George L. Sutphin⁴  Daniel Carr⁴  Christopher J. Murakami⁴  Autumn Tocchi⁴  Bo Xian¹  Weiyang Chen¹  Tao Yu¹  Sarani Goswami⁴  Sean Higgins⁴  Mollie Holmberg⁴  Ki-Soo Jeong⁴  Jin R. Kim⁴  Shannon Klum⁴  Eric Liao⁴  Michael S. Lin⁴  Winston Lo⁴  Hillary Miller⁴  Brady Olsen⁴  Zhao J. Peng⁴  Tom Pollard⁴  Prarthana Pradeep⁴  Dillon Pruett⁴  Dilreet Rai⁴  Vanessa Ros⁴  Minnie Singh⁴  Benjamin L. Spector⁴  Helen Vander Wende⁴  Elroy H. An⁴  Marissa Fletcher⁴  Monika Jelic⁴  Peter S. Rabinovitch⁴  Michael J. MacCoss³  Jing-Dong J. Han¹  Brian K. Kennedy² 

[1] CAS Key Laboratory for Computational Biology, CAS-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China;Buck Institute for Age Research, Novato, CA, USA;Department of Genome Sciences, University of Washington, Seattle, WA, USA;Department of Pathology, University of Washington, Seattle, WA, USA

关键词: aging;    replicative lifespan;    longevity;    yeast;    dietary restriction;    mitochondria;    mitochondrial unfolded protein response;   

DOI  :  10.1111/acel.12130

来源: Wiley

【 摘 要 】

Summary

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 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 Caenorhabditis elegans. These observations define conserved molecular processes that underlie genotype-dependent effects of DR that may be important modulators of DR in higher organisms.

【 授权许可】

Unknown   
© 2013 the Anatomical Society and John Wiley & Sons Ltd