Autophagy And Aging

From IT SPb Academy

Contents 1 Reviews 2 Increasing of basal insulin receptor activity with age 3 Autophagy decline during aging 4 CMA - Chaperon Mediated Autophagy and aging 5 Autophagy and mTOR 6 Drugs enhancing autophagy

Reviews

Salminen A and Kaarniranta K. Regulation of the aging process by autophagy. 2009. Cell

2008 Cuervo Autophagy and aging: keeping that old broom working

Increasing of basal insulin receptor activity with age

Droge, W. and Kinscherf, R. (2008) Aberrant insulin receptor signaling and amino acid homeostasis as a major cause of oxidative stress in aging. Antioxid. Redox Signal. 10, 661–678

Autophagy decline during aging

• Grune, T. et al. (2004) Decreased proteolysis caused by protein aggregates, inclusion bodies, plaques, lipofuscin, ceroid, and "aggresomes" during oxidative stress, aging, and disease. Int. J. Biochem. Cell Biol. 36, 2519–2530

(From Cuervo 2008) Measurement of autophagic activity (the rate of degradation of long-lived proteins) in rodent livers revealed an age-dependent decrease in lysosomal-mediated degradation that correlated with an increase in damaged proteins in this organ:

• Vittorini, S. et al. (1999) The age-related accumulation of protein carbonyl in rat liver correlates with the age-related decline in liver proteolytic activities. J. Gerontol. A Biol. Sci. Med Sci. 54, B318–B323

CMA - Chaperon Mediated Autophagy and aging

• Cuervo, A.M. and Dice, J.F. (2000) Age-related decline in chaperone mediated autophagy. J. Biol. Chem. 275, 31505–31513

These studies were able to establish that the reduced efficiency was due to the progressive age-related decrease in the expression of LAMP-2A protein, the receptor protein in CMA uptake.

• Zhang, C. and Cuervo, A.M. (2008) Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat. Med. 14, 959–965

The mechanism of the LAMP-2A decline in lysosomes during aging seems to be post-transcriptional because aging does not affect the transcription efficiency of LAMP-2A

• Kiffin, R. et al. (2007) Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age. J. Cell Sci. 120, 782–791

Heat shock protein HSP90 is the key component in the assembly of the LAMP-2A complex

• Nardai, G. et al. (2002) Chaperone function and chaperone overload in the aged. A preliminary analysis. Exp. Gerontol. 37, 1257–1262

• Shibata, M. et al. (2006) Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J. Biol. Chem. 281, 14474–14485

Autophagy and mTOR

• Pattingre, S. et al. (2008) Regulation of macroautophagy by mTOR and Beclin 1 complexes. Biochimie 90, 313–323

From(Cuervj, 2008): Two conjugation events – a protein to protein and a protein to lipid conjugation – and two intracellular kinase complexes – the beclin–VPS34 (named for vacuolar protein sorting) complex and the mTOR (mammalian target of rapamycin) complex – act coordinately to modulate formation, sealing and fusion of the autophagic compartments with lysosomes

• Yorimitsu, T. and Klionsky, D.J. (2005) Autophagy: molecular

machinery for self-eating. Cell Death Differ. 12, 1542–1552

• Ohsumi, Y. (2001) Molecular dissection of autophagy: two ubiquitinlike

systems. Nat. Rev. Mol. Cell Biol. 2, 211–216

Drugs enhancing autophagy

• Donati, A. et al. (2008) In vivo effect of an antilipolytic drug (3,50-

dimethylpyrazole) on autophagic proteolysis and autophagy-related gene expression in rat liver. Biochem. Biophys. Res. Commun. 366, 786–792