作者
Sarah J Mitchell, Julio Madrigal-Matute, Morten Scheibye-Knudsen, Evandro Fang, Miguel Aon, José A González-Reyes, Sonia Cortassa, Susmita Kaushik, Marta Gonzalez-Freire, Bindi Patel, Devin Wahl, Ahmed Ali, Miguel Calvo-Rubio, María I Burón, Vincent Guiterrez, Theresa M Ward, Hector H Palacios, Huan Cai, David W Frederick, Christopher Hine, Filomena Broeskamp, Lukas Habering, John Dawson, T Mark Beasley, Junxiang Wan, Yuji Ikeno, Gene Hubbard, Kevin G Becker, Yongqing Zhang, Vilhelm A Bohr, Dan L Longo, Placido Navas, Luigi Ferrucci, David A Sinclair, Pinchas Cohen, Josephine M Egan, James R Mitchell, Joseph A Baur, David B Allison, R Michael Anson, José M Villalba, Frank Madeo, Ana Maria Cuervo, Kevin J Pearson, Donald K Ingram, Michel Bernier, Rafael De Cabo
发表日期
2016/6/14
期刊
Cell metabolism
卷号
23
期号
6
页码范围
1093-1112
出版商
Cell Press
简介
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 …
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SJ Mitchell, J Madrigal-Matute, M Scheibye-Knudsen… - Cell metabolism, 2016