| Literature DB >> 27304509 |
Sarah J Mitchell1, Julio Madrigal-Matute2, Morten Scheibye-Knudsen3, Evandro Fang4, Miguel Aon5, José A González-Reyes6, Sonia Cortassa5, Susmita Kaushik2, Marta Gonzalez-Freire1, Bindi Patel2, Devin Wahl1, Ahmed Ali1, Miguel Calvo-Rubio6, María I Burón6, Vincent Guiterrez1, Theresa M Ward1, Hector H Palacios1, Huan Cai7, David W Frederick8, Christopher Hine9, Filomena Broeskamp10, Lukas Habering10, John Dawson11, T Mark Beasley11, Junxiang Wan12, Yuji Ikeno13, Gene Hubbard13, Kevin G Becker14, Yongqing Zhang14, Vilhelm A Bohr4, Dan L Longo14, Placido Navas15, Luigi Ferrucci1, David A Sinclair16, Pinchas Cohen12, Josephine M Egan7, James R Mitchell9, Joseph A Baur8, David B Allison11, R Michael Anson1, José M Villalba6, Frank Madeo10, Ana Maria Cuervo2, Kevin J Pearson17, Donald K Ingram18, Michel Bernier1, Rafael de Cabo19.
Abstract
Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions. Published by Elsevier Inc.Entities:
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Year: 2016 PMID： 27304509 PMCID： PMC4911707 DOI： 10.1016/j.cmet.2016.05.027
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287