Selective autophagy in the maintenance of cellular homeostasis in aging organisms

被引:92
作者
Hubbard, Vanessa M. [3 ]
Valdor, Rut [3 ]
Macian, Fernando [2 ,3 ]
Cuervo, Ana Maria [1 ,2 ]
机构
[1] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA
[2] Albert Einstein Coll Med, Inst Aging Res, Bronx, NY 10461 USA
[3] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA
关键词
Aging; Chaperones; Health-span; Longevity; Lysosomes; Neurodegeneration; Proteotoxicity; CHAPERONE-MEDIATED AUTOPHAGY; AGE-RELATED DECLINE; LIFE-SPAN EXTENSION; RAT-LIVER; ALPHA-SYNUCLEIN; PEPTIDE SEQUENCES; LYSOSOMAL DEGRADATION; ENDOPLASMIC-RETICULUM; PROTEIN-DEGRADATION; CYTOSOLIC PROTEINS;
D O I
10.1007/s10522-011-9331-x
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
030301 [社会学]; 100201 [内科学];
摘要
Altered cellular homeostasis, accumulation of damaged non-functional organelles and presence of protein inclusions are characteristics shared by almost all types of differentiated cells in aged organisms. Cells rely on quality control mechanisms to prevent the occurrence of these events and the subsequent cellular compromise associated with them. What goes wrong in aging cells? Growing evidence supports gradual malfunctioning with age of the cellular quality control systems. In this review, we focus on autophagy, a catabolic process that contributes to the maintenance of cellular homeostasis through the degradation of unwanted and damaged components in lysosomes. We describe recent advances on the molecular characterization of this process, its different variants and the multiplicity of functions attributed to them. Autophagic dysfunction has been identified in severe human disorders, many of which worsen with age. We comment on the contribution of an adequate autophagic function to longevity, and the negative impact on health-span of the age-dependent decline in autophagic function.
引用
收藏
页码:21 / 35
页数:15
相关论文
共 139 条
[1]
Agarraberes FA, 2001, J CELL SCI, V114, P2491
[2]
An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation [J].
Agarraberes, FA ;
Terlecky, SR ;
Dice, JF .
JOURNAL OF CELL BIOLOGY, 1997, 137 (04) :825-834
[3]
Oxidative stress, apoptosis, and proteolysis in skeletal muscle repair after unloading [J].
Andrianjafiniony, Tina ;
Dupre-Aucouturier, Sylvie ;
Letexier, Dominique ;
Couchoux, Harold ;
Desplanches, Dominique .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2010, 299 (02) :C307-C315
[4]
ANIENTO F, 1993, J BIOL CHEM, V268, P10463
[5]
Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum [J].
Axe, Elizabeth L. ;
Walker, Simon A. ;
Manifava, Maria ;
Chandra, Priya ;
Roderick, H. Llewelyn ;
Habermann, Anja ;
Griffiths, Gareth ;
Ktistakis, Nicholas T. .
JOURNAL OF CELL BIOLOGY, 2008, 182 (04) :685-701
[6]
The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane [J].
Bandyopadhyay, Urmi ;
Kaushik, Susmita ;
Varticovski, Lyuba ;
Cuervo, Ana Maria .
MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (18) :5747-5763
[7]
Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans [J].
Bass, Timothy M. ;
Weinkove, David ;
Houthoofd, Koen ;
Gems, David ;
Partridge, Linda .
MECHANISMS OF AGEING AND DEVELOPMENT, 2007, 128 (10) :546-552
[8]
Resveratrol improves health and survival of mice on a high-calorie diet [J].
Baur, Joseph A. ;
Pearson, Kevin J. ;
Price, Nathan L. ;
Jamieson, Hamish A. ;
Lerin, Carles ;
Kalra, Avash ;
Prabhu, Vinayakumar V. ;
Allard, Joanne S. ;
Lopez-Lluch, Guillermo ;
Lewis, Kaitlyn ;
Pistell, Paul J. ;
Poosala, Suresh ;
Becker, Kevin G. ;
Boss, Olivier ;
Gwinn, Dana ;
Wang, Mingyi ;
Ramaswamy, Sharan ;
Fishbein, Kenneth W. ;
Spencer, Richard G. ;
Lakatta, Edward G. ;
Le Couteur, David ;
Shaw, Reuben J. ;
Navas, Placido ;
Puigserver, Pere ;
Ingram, Donald K. ;
de Cabo, Rafael ;
Sinclair, David A. .
NATURE, 2006, 444 (7117) :337-342
[9]
Selective degradation of peroxisomes in yeasts [J].
Bellu, AR ;
Kiel, JAKW .
MICROSCOPY RESEARCH AND TECHNIQUE, 2003, 61 (02) :161-170
[10]
The anti-ageing effects of caloric restriction may involve stimulation of macroautophagy and lysosomal degradation, and can be intensified pharmacologically [J].
Bergamini, E ;
Cavallini, G ;
Donati, A ;
Gori, Z .
BIOMEDICINE & PHARMACOTHERAPY, 2003, 57 (5-6) :203-208