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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: 11.6). 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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    Biochemical and Biophysical Research Communications 04/2015; 462(2). DOI:10.1016/j.bbrc.2015.04.084 · 2.28 Impact Factor
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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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    • "How do the IIS and mTOR pathway contribute to the aging phenotype? A continuous stimulation of the IIS and mTOR pathways leads to a higher risk of aging-related diseases and reduced lifespan via reduced autophagy (less clearance of protein aggregates and cellular organelles), increased protein agglomeration and proteotoxicity (mTOR activation leads to increased protein production and reduced protein clearance), inflammation, reduced expression of antioxidant proteins, mitochondrial dysfunction, and other mechanisms (Kenyon, 2010; Fontana et al., 2010; Johnson et al., 2013; Cuervo, 2008). These mechanisms increase the risk of insulin resistance (Shah et al., 2004), atherosclerosis (Martinet et al., 2014), cardiomyopathy (Willis & Patterson, 2013), neurodegenerative diseases (O'Neill et al., 2012, 2013), cancer (Martini et al., 2014), osteoporosis (Glantschnig et al., 2003) and other aging-related diseases and symptoms. "
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