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

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.

SUBMITTER: Lanza IR

PROVIDER: S-EPMC3544078 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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

Lanza Ian R IR Zabielski Piotrek P Klaus Katherine A KA Morse Dawn M DM Heppelmann Carrie J CJ Bergen H Robert HR Dasari Surendra S Walrand Stephane S Short Kevin R KR Johnson Matthew L ML Robinson Matthew M MM Schimke Jill M JM Jakaitis Daniel R DR Asmann Yan W YW Sun Zhifu Z Nair K Sreekumaran KS

Cell metabolism 20121201 6

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 occu ...[more]

PMID: 23217257

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Project description:UnlabelledThere is a debate over the independent effects of aerobic fitness and body fatness on mortality and disease risks.PurposeTo determine whether a 25% energy deficit that produces equal change in body fatness leads to greater cardiometabolic benefits when aerobic exercise is included.MethodsThirty-six overweight participants (16 males/20 females) (39 +/- 1 yr; 82 +/- 2 kg; body mass index = 27.8 +/- 0.3 kg x m2, mean +/- SEM) were randomized to one of three groups (n = 12 for each) for a 6-month intervention: control (CO, weight-maintenance diet), caloric restriction (CR, 25% reduction in energy intake), or caloric restriction plus aerobic exercise (CR + EX, 12.5% reduction in energy intake plus 12.5% increase in exercise energy expenditure). Food was provided during weeks 1-12 and 22-24. Changes in fat mass, visceral fat, VO2peak (graded treadmill test), muscular strength (isokinetic knee extension/flexion), blood lipids, blood pressure, and insulin sensitivity/secretion were compared.ResultsAs expected, VO2peak was significantly improved after 6 months of intervention in CR + EX only (22 +/- 5% vs 7 +/- 5% in CR and -5 +/- 3% in CO), whereas isokinetic muscular strength did not change. There was no difference in the losses of weight, fat mass, or visceral fat and changes in systolic blood pressure (BP) between the intervention groups. However, only CR + EX had a significant decrease in diastolic BP (-5 +/- 3% vs -2 +/- 2% in CR and -1 +/- 2% in CO), in low-density lipoprotein (LDL) cholesterol (-13 +/- 4% vs -6 +/- 3% in CR and 2 +/- 4% in CO), and a significant increase in insulin sensitivity (66 +/- 22% vs 40 +/- 20% in CR and 1 +/- 11% in CO).ConclusionsDespite similar effect on fat losses, combining CR with exercise increased aerobic fitness in parallel with improved insulin sensitivity, LDL cholesterol, and diastolic BP. The results lend support for inclusion of an exercise component in weight loss programs to improve metabolic fitness.

Dataset Information

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

Publications

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

Similar Datasets

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