Mitochondrial biogenesis and healthy aging - PubMed (original) (raw)

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Mitochondrial biogenesis and healthy aging

Guillermo López-Lluch et al. Exp Gerontol. 2008 Sep.

Abstract

Aging is associated with an overall loss of function at the level of the whole organism that has origins in cellular deterioration. Most cellular components, including mitochondria, require continuous recycling and regeneration throughout the lifespan. Mitochondria are particularly susceptive to damage over time as they are the major bioenergetic machinery and source of oxidative stress in cells. Effective control of mitochondrial biogenesis and turnover, therefore, becomes critical for the maintenance of energy production, the prevention of endogenous oxidative stress and the promotion of healthy aging. Multiple endogenous and exogenous factors regulate mitochondrial biogenesis through the peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). Activators of PGC-1alpha include nitric oxide, CREB and AMPK. Calorie restriction (CR) and resveratrol, a proposed CR mimetic, also increase mitochondrial biogenesis through activation of PGC-1alpha. Moderate exercise also mimics CR by inducing mitochondrial biogenesis. Negative regulators of PGC-1alpha such as RIP140 and 160MBP suppress mitochondrial biogenesis. Another mechanism involved in mitochondrial maintenance is mitochondrial fission/fusion and this process also involves an increasing number of regulatory proteins. Dysfunction of either biogenesis or fission/fusion of mitochondria is associated with diseases of the neuromuscular system and aging, and a greater understanding of the regulation of these processes should help us to ultimately control the aging process.

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Figures

Figure 1

Figure 1. PGC-1α regulating network

PGC-1α is at the center of a complex network of signals affected by metabolic, nutritional and environmental factors that modulate (e.g. through transcriptional and post-translational modifications) PGC-1α activity and thereby mitochondrial biogenesis. To date, very few negative regulators of PGC-1α have been found. However, increasing interest in this protein suggests the present regulatory network will grow yet more complex in the future.

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