title: Mitochondria as sources and targets of damage in cellular aging.
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.
authors.affiliation: Department of Physiology, University of Valencia, Fundacion Investigacion Hospital Clinico Universitario/INCLIVA, Valencia, Spain. carmen.gomez@uv.es
authors.forename: Mari Carmen
authors.initials: MC
authors.lastname: Gomez-Cabrera
authors.forename: Fabian
authors.initials: F
authors.lastname: Sanchis-Gomar
authors.forename: Rebeca
authors.initials: R
authors.lastname: Garcia-Valles
authors.forename: Helios
authors.initials: H
authors.lastname: Pareja-Galeano
authors.forename: Juan
authors.initials: J
authors.lastname: Gambini
authors.forename: Consuelo
authors.initials: C
authors.lastname: Borras
authors.forename: Jose
authors.initials: J
authors.lastname: Viña
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology*; D004249:DNA Damage / Q000235:genetics; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D000975:Antioxidants; D005609:Free Radicals