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Autophagy and aging: connecting nutritional‐regulated catabolism and cellular quality control
Author(s) -
Cuervo Ana Maria
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.425.3
Subject(s) - autophagy , microbiology and biotechnology , catabolism , cytosol , intracellular , homeostasis , oxidative stress , biology , protein turnover , chemistry , biochemistry , metabolism , enzyme , protein biosynthesis , apoptosis
Autophagy is a basic catabolic cellular process by which intracellular components are delivered to lysosomes for degradation. Activation of autophagy obeys to two different cellular needs, as an internal source of energy and as a mechanism for removal of damage or no longer functional structures. Malfunctioning of autophagy has been described with age. Our studies have focused primarily in one type of autophagy known as chaperone‐mediated autophagy (CMA), which mediates selective degradation of cytosolic proteins. Maximal activation of CMA is attained during prolonged nutritional stress, mild‐oxidative stress or toxin exposure. CMA activity declines with age due to a decrease in the levels of the lysosomal receptor that mediates substrate translocation. Interestingly, we have found that caloric restriction results in constitutive activation of this form of autophagy. As part of our ongoing studies, we have developed a transgenic mouse model in which we can preserve normal CMA activity until advanced ages in liver by correcting the age‐related defect in this pathway in this organ. Old mice with preserved CMA activity display improved cellular homeostasis, better resistance to stress and a general improvement in basic liver functions. We will use similar approaches to evaluate the importance of maintaining proper energetic balance and adequate protein removal until advanced ages in different organs.