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Antioxid Redox Signal. 2013 Jul 20;19(3):310-20. doi: 10.1089/ars.2012.4866. Epub 2012 Oct 15.

Mitochondrial metabolic reprogramming induced by calorie restriction.

Author information

1
Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.

Abstract

SIGNIFICANCE:

Calorie restriction (CR) is a known intervention that delays most aging processes. Most of the beneficial effects of CR are mediated by improved maintenance of mitochondrial performance in aged individuals. The control of mitochondrial biogenesis, apoptosis, and protein turnover is required for healthy aging. CR is able to induce molecular mechanisms that preserve oxidative capacity and decrease oxidative damage.

RECENT ADVANCES AND CRITICAL ISSUES:

Published data indicate that peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is activated in old animals under CR conditions compared to ad libitum counterparts, enhancing mitochondrial biogenesis. Molecular regulation of PGC-1α has recently attracted significant research interest. We discuss the master regulators of energy metabolism such as AMP-activated protein kinase and sirtuin 1 among others that have been demonstrated to activate mitochondrial biogenesis through increased PGC-1α activity at transcriptional and post-translational levels. Additionally, we describe the latest findings that explain how CR promotes mitochondrial efficiency and decreases mitochondrial-derived oxidative damage.

FUTURE DIRECTIONS:

Understanding the beneficial mitochondrial changes conferred by CR will aid design of therapies for age-related diseases and help slow the aging process. Given the difficulty for humans to adhere to CR, we also explore new molecules that have been proposed during the last years to mimic the CR phenotype and their potential as future therapeutics.

PMID:
22901095
PMCID:
PMC3691909
DOI:
10.1089/ars.2012.4866
[Indexed for MEDLINE]
Free PMC Article

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