Article

Autophagy and aging: keeping that old broom working. Trends Genet

Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center and Institute for Aging Studies, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Ullmann B. 611, Bronx, NY 10461, USA.
Trends in Genetics (Impact Factor: 9.92). 01/2009; 24(12):604-12. DOI: 10.1016/j.tig.2008.10.002
Source: PubMed

ABSTRACT

Autophagy, a highly conserved mechanism of quality control inside cells, is essential for the maintenance of cellular homeostasis and for the orchestration of an efficient cellular response to stress. The decrease in autophagic activity observed in almost all cells and tissues as organisms age was proposed to contribute to different aspects of the aging phenotype and to the aggravation of detrimental age-related diseases. The recent advances in our understanding of the molecular mechanisms underlying autophagy and the identification of the subset of genes involved in this process has enabled the use of genetic manipulations to start testing this hypothesis. Here, I review the recent genetic evidence in support of tight connections between autophagy, health span and aging.

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    • "UPS is the major mechanism for protein quality control through selective degradation of damaged/unfolded proteins [5]. Autophagy also degrades cytosolic materials from proteins to organelles, especially insoluble protein aggregates [6]. Accordingly , altered UPS function and autophagy degradation are frequently found in chronic neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS) [7] [8]. "
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    • "Accordingly, we report here that the alteration in APP binding to SorLA (and likely to other adaptors) leads to APP accumulation in LEs and lysosomes and to autophagic defects, which are considered a major risk factor for AD and dementia during aging (Cuervo, 2008; Salminen and Kaarniranta, 2009). "
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