Portal de Periódicos da CAPES

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

2016; Cell Press; Volume: 23; Issue: 6 Linguagem: Inglês

10.1016/j.cmet.2016.05.027

1932-7420

Sarah J. Mitchell, Julio Madrigal‐Matute, Morten Scheibye‐Knudsen, Evandro Fei Fang, Miguel A. Aon, José A. González‐Reyes, Sonia Cortassa, Susmita Kaushik, Marta González‐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 B. Hubbard, Kevin G. Becker, Yongqing Zhang, Vilhelm A. Bohr, Dan L. Longo, Plácido Navas, Luigi Ferrucci, David Sinclair, Pinchas Cohen, Josephine M. Egan, James R. Mitchell, Joseph A. Baur, David B. Allison, R. Michael Anson, José M. Villalba, Frank Madeo, Ana María Cuervo, Kevin J. Pearson, Donald K. Ingram, Michel Bernier, Rafael de Cabo,

Genetics, Aging, and Longevity in Model Organisms

Summary 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.