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Title: Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice.
Authors: Mitchell SJ; Madrigal-Matute J; Scheibye-Knudsen M; Fang E; Aon M; Gonzalez-Reyes JA; Cortassa S; Kaushik S; Gonzalez-Freire M; Patel B; Wahl D; Ali A; Calvo-Rubio M; Buron MI; Guiterrez V; Ward TM; Palacios HH; Cai H; Frederick DW; Hine C; Broeskamp F; Habering L; Dawson J; Beasley TM; Wan J; Ikeno Y; Hubbard G; Becker KG; Zhang Y; Bohr VA; Longo DL; Navas P; Ferrucci L; Sinclair DA; Cohen P; Egan JM; Mitchell JR; Baur JA; Allison DB; Anson RM; Villalba JM; Madeo F; Cuervo AM; Pearson KJ; Ingram DK; Bernier M; de Cabo R
Journal: Cell Metab
Volume: 23
Issue: 6
Year: 2016
Pages: 1093-1112
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.
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J:256619  Mouse Genome Informatics
27304509  National Library of Medicine/PubMed