Accessible Requires Authentication Published by De Gruyter February 1, 2012

Mitochondria as sources and targets of damage in cellular aging

Mari Carmen Gomez-Cabrera, Fabian Sanchis-Gomar, Rebeca Garcia-Valles, Helios Pareja-Galeano, Juan Gambini, Consuelo Borras and Jose Viña

Abstract

Mitochondria are considered as the most important cellular sources and targets of free radicals. They are also a source of signalling molecules that regulate cell cycle, proliferation, and apoptosis. Denham Harman postulated the free radical theory of aging in 1956. Previously Rebecca Gershman showed that radiation toxicity could be attributed to free radical damage. Subsequently, Jaime Miquel formulated the mitochondrial free radical theory of aging. We have shown that mitochondrial size, membrane potential, inner membrane mass and peroxide production is altered inside cells in old animals. These result in an increase in the oxidative damage to mitochondrial DNA with aging that can be prevented by antioxidant supplementation. Aging is also associated with a lower renewal of mitochondria. This is mainly due to the lack of reactivity of proliferator-activated receptor-γ (PPAR-γ) coactivator 1α (PGC-1α) in old animals. PGC-1α acts as a master regulator of energy metabolism and mitochondrial biogenesis and recent evidence shows that it interacts with p53 and telomerase. The promotion of mitochondriogenesis is critical to prevent aging. In skeletal muscle it has relevance to prevent sarcopenia and frailty.


Corresponding author: Mari Carmen Gomez-Cabrera, PhD, Department of Physiology, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez, 15 46010 Valencia, SpainPhone: +(34) 96 386 46 50, Fax: +(34) 96 386 46 42

Received: 2011-10-30
Accepted: 2011-12-25
Published Online: 2012-02-01
Published in Print: 2012-08-01

©2012 by Walter de Gruyter Berlin Boston