Mitochondria as sources and targets of damage in cellular aging

被引:54
作者
Carmen Gomez-Cabrera, Mari [1 ,2 ]
Sanchis-Gomar, Fabian [1 ,2 ]
Garcia-Valles, Rebeca [1 ,2 ]
Pareja-Galeano, Helios [1 ]
Gambini, Juan [1 ]
Borras, Consuelo [1 ]
Vina, Jose [1 ]
机构
[1] Univ Valencia, Dept Physiol, Fdn Invest Hosp Clin Univ INCLIVA, Valencia 46010, Spain
[2] Univ Valencia, Fac Med, Dept Physiol, Valencia 46010, Spain
关键词
antioxidants; DNA damage; longevity; oxidative stress; mitochondrial biogenesis; PGC-1; CALORIC RESTRICTION; OXIDATIVE DAMAGE; METABOLIC DISEASE; AGE; MUSCLE; DNA; CANCER; STRESS; TELOMERASE; EXERCISE;
D O I
10.1515/cclm-2011-0795
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
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 Miguel 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 mitochondria! 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-gamma (PPAR-gamma) coactivator 1 alpha (PGC-1 alpha) in old animals. PGC-1 alpha 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.
引用
收藏
页码:1287 / 1295
页数:9
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