Chronic caloric restriction preserves mitochondrial function in senescence without increasing mitochondrial biogenesis

Ian R Lanza, Piotrek Zabielski, Katherine A. Klaus, Dawn M. Morse, Carrie J. Heppelmann, Harold Robert (Bob) III Bergen, Surendra Dasari, Stephane Walrand, Kevin R. Short, Matthew L. Johnson, Matthew M. Robinson, Jill M. Schimke, Daniel R. Jakaitis, Yan Asmann, Zhifu D Sun, K Sreekumaran Nair

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)777-788
Number of pages12
JournalCell Metabolism
Volume16
Issue number6
DOIs
StatePublished - Dec 5 2012

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Caloric Restriction
Organelle Biogenesis
Muscle Mitochondrion
Mitochondrial Proteins
Oxidants
Proteomics
DNA Damage
Antioxidants
Genome

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Chronic caloric restriction preserves mitochondrial function in senescence without increasing mitochondrial biogenesis. / Lanza, Ian R; Zabielski, Piotrek; Klaus, Katherine A.; Morse, Dawn M.; Heppelmann, Carrie J.; Bergen, Harold Robert (Bob) III; Dasari, Surendra; Walrand, Stephane; Short, Kevin R.; Johnson, Matthew L.; Robinson, Matthew M.; Schimke, Jill M.; Jakaitis, Daniel R.; Asmann, Yan; Sun, Zhifu D; Nair, K Sreekumaran.

In: Cell Metabolism, Vol. 16, No. 6, 05.12.2012, p. 777-788.

Research output: Contribution to journalArticle

Lanza, IR, Zabielski, P, Klaus, KA, Morse, DM, Heppelmann, CJ, Bergen, HRBIII, Dasari, S, Walrand, S, Short, KR, Johnson, ML, Robinson, MM, Schimke, JM, Jakaitis, DR, Asmann, Y, Sun, ZD & Nair, KS 2012, 'Chronic caloric restriction preserves mitochondrial function in senescence without increasing mitochondrial biogenesis', Cell Metabolism, vol. 16, no. 6, pp. 777-788. https://doi.org/10.1016/j.cmet.2012.11.003
Lanza, Ian R ; Zabielski, Piotrek ; Klaus, Katherine A. ; Morse, Dawn M. ; Heppelmann, Carrie J. ; Bergen, Harold Robert (Bob) III ; Dasari, Surendra ; Walrand, Stephane ; Short, Kevin R. ; Johnson, Matthew L. ; Robinson, Matthew M. ; Schimke, Jill M. ; Jakaitis, Daniel R. ; Asmann, Yan ; Sun, Zhifu D ; Nair, K Sreekumaran. / Chronic caloric restriction preserves mitochondrial function in senescence without increasing mitochondrial biogenesis. In: Cell Metabolism. 2012 ; Vol. 16, No. 6. pp. 777-788.
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