Mitochondrial energy metabolism and ageing.
Ageing can be defined as "a progressive, generalized impairment of function, resulting in an increased vulnerability to environmental challenge and a growing risk of disease and death". Ageing is likely a multifactorial process caused by accumulated damage to a variety of cellular components. During the last 20 years, gerontological studies have revealed different molecular pathways involved in the ageing process and pointed out mitochondria as one of the key regulators of longevity. Increasing age in mammals correlates with increased levels of mitochondrial DNA (mtDNA) mutations and a deteriorating respiratory chain function. Experimental evidence in the mouse has linked increased levels of somatic mtDNA mutations to a variety of ageing phenotypes, such as osteoporosis, hair loss, graying of the hair, weight reduction and decreased fertility. A mosaic respiratory chain deficiency in a subset of cells in various tissues, such as heart, skeletal muscle, colonic crypts and neurons, is typically found in aged humans. It has been known for a long time that respiratory chain-deficient cells are more prone to undergo apoptosis and an increased cell loss is therefore likely of importance in the age-associated mitochondrial dysfunction. In this review, we would like to point out the link between the mitochondrial energy balance and ageing, as well as a possible connection between the mitochondrial metabolism and molecular pathways important for the lifespan extension.
Bratic
Ivana
I
Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, D-50674 Cologne, Germany.
Trifunovic
Aleksandra
A
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D031204:Caloric Restriction; D019069:Cell Respiration; D004579:Electron Transport; D004734:Energy Metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D010085:Oxidative Phosphorylation; D015398:Signal Transduction
D007328:Insulin; D000255:Adenosine Triphosphate