Autophagy genes and ageing

被引:132
作者
Vellai, T. [1 ]
机构
[1] Eotvos Lorand Univ, Dept Genet, H-1117 Budapest, Hungary
关键词
autophagy; ageing; longevity pathways; cellular toxin; mitochondria; lysosomes; EXTENDS LIFE-SPAN; CAENORHABDITIS-ELEGANS; DIETARY RESTRICTION; C; ELEGANS; CELL-DEATH; PROTEIN-DEGRADATION; REGULATES AUTOPHAGY; MOLECULAR MACHINERY; FAMILY-MEMBER; LONGEVITY;
D O I
10.1038/cdd.2008.126
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ageing in divergent animal phyla is influenced by several evolutionarily conserved signalling pathways, mitochondrial activity and various environmental factors such as nutrient availability and temperature. Although ageing is a multifactorial process with many mechanisms contributing to the decline, the intracellular accumulation of damaged proteins and mitochondria is a feature common to all aged cells. Autophagy (cellular self-eating) -a lysosome-mediated catabolic process of eukaryotic cells to digest their own constituents -is a major route for the bulk degradation of aberrant cytosolic macromolecules and organelles. Indeed, genetic studies show that autophagy-related genes are required for lifespan extension in various long-lived mutant nematodes and promote survival in worms and flies exposed to prolonged starvation. These data implicate autophagy in ageing control. Furthermore, results in Drosophila demonstrate that promoting basal expression of the autophagy gene Atg8 in the nervous system extends lifespan by 50%, thereby providing evidence that the autophagy pathway regulates the rate at which the tissues age. In this review, the molecular mechanisms by which autophagy genes interact with longevity pathways in diverse organisms ranging from yeast to mammals are discussed.
引用
收藏
页码:94 / 102
页数:9
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