Journal of Clinical & Experimental Pathology · 2012 · 129 citations · 132 references
Life SciencesCell BiologyMolecular BiologyAgingAutophagyMolecular Cell BiologyAutophagy In DiseaseAutophagy In Stress ResponsesAutophagy ModulationAutophagy RegulationCellular AgingLysosomal DysfunctionAutophagic ClearanceAutophagosome Cargo DegradationAutophagy ImpairmentAutophagy In Metabolic HomeostasisAutophagy PathwayAutophagy Under StressSingle-gene MutationsYeast Autophagy
Autophagy is a cytoplasmic catabolic process that protects the cell against stressful conditions. Damaged cellular components are funneled by autophagy into the lysosomes, where they are degraded and can be re-used as alternative building blocks for protein synthesis and cellular repair. In contrast, aging is the gradual failure over time of cellular repair mechanisms that leads to the accumulation of molecular and cellular damage and loss of function. The cell's capacity for autophagic degradation also declines with age, and this in itself may contribute to the aging process. Studies in model organisms ranging from yeast to mice have shown that single-gene mutations can extend lifespan in an evolutionarily conserved fashion, and provide evidence that the aging process can be modulated. Interestingly, autophagy is induced in a seemingly beneficial manner by many of the same perturbations that extend lifespan, including mutations in key signaling pathways such as the insulin/IGF-1 and TOR pathways. Here, we review recent progress, primarily derived from genetic studies with model organisms, in understanding the role of autophagy in aging and age-related diseases.
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