TitleChronic caloric restriction preserves mitochondrial function in senescence without increasing mitochondrial biogenesis.
Publication TypeJournal Article
Year of Publication2012
AuthorsLanza, IR, Zabielski, P, Klaus, KA, Morse, DM, Heppelmann, CJ, H Bergen, R, Dasari, S, Walrand, S, Short, KR, Johnson, ML, Robinson, MM, Schimke, JM, Jakaitis, DR, Asmann, YW, Sun, Z, K Nair, S
JournalCell Metab
Date Published2012 Dec 05
KeywordsAging, Animals, Caloric Restriction, DNA, Mitochondrial, Down-Regulation, Electron Transport Complex I, Electron Transport Complex II, Gene Expression Profiling, Mice, Mitochondria, Mitochondrial Proteins, Mitochondrial Turnover, Muscle Proteins, Muscle, Skeletal, Oxidative Stress, Proteomics, Transcriptome

Caloric restriction (CR) mitigates many detrimental effects of aging and prolongs life span. CR has been suggested to increase mitochondrial biogenesis, thereby attenuating age-related declines in mitochondrial function, a concept that is challenged by recent studies. Here we show that lifelong CR in mice prevents age-related loss of mitochondrial oxidative capacity and efficiency, measured in isolated mitochondria and permeabilized muscle fibers. We find that these beneficial effects of CR occur without increasing mitochondrial abundance. Whole-genome expression profiling and large-scale proteomic surveys revealed expression patterns inconsistent with increased mitochondrial biogenesis, which is further supported by lower mitochondrial protein synthesis with CR. We find that CR decreases oxidant emission, increases antioxidant scavenging, and minimizes oxidative damage to DNA and protein. These results demonstrate that CR preserves mitochondrial function by protecting the integrity and function of existing cellular components rather than by increasing mitochondrial biogenesis.

Alternate JournalCell Metab.
PubMed ID23217257
PubMed Central IDPMC3544078
Grant ListKL2TR000136-07 / TR / NCATS NIH HHS / United States
T32 DK007198 / DK / NIDDK NIH HHS / United States
KL2 TR000136 / TR / NCATS NIH HHS / United States
R01-AG09531 / AG / NIA NIH HHS / United States
R01 AG009531 / AG / NIA NIH HHS / United States