PMID- 25620427
OWN - NLM
STAT- MEDLINE
DCOM- 20151214
LR  - 20200630
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Print)
IS  - 1474-9718 (Linking)
VI  - 14
IP  - 2
DP  - 2015 Apr
TI  - Loss of hepatic chaperone-mediated autophagy accelerates proteostasis failure in 
      aging.
PG  - 249-64
LID - 10.1111/acel.12310 [doi]
AB  - Chaperone-mediated autophagy (CMA), a cellular process that contributes to 
      protein quality control through targeting of a subset of cytosolic proteins to 
      lysosomes for degradation, undergoes a functional decline with age. We have used 
      a mouse model with liver-specific defective CMA to identify changes in 
      proteostasis attributable to reduced CMA activity in this organ with age. We have 
      found that other proteolytic systems compensate for CMA loss in young mice which 
      helps to preserve proteostasis. However, these compensatory responses are not 
      sufficient for protection against proteotoxicity induced by stress (oxidative 
      stress, lipid challenges) or associated with aging. Livers from old mice with CMA 
      blockage exhibit altered protein homeostasis, enhanced susceptibility to 
      oxidative stress and hepatic dysfunction manifested by a diminished ability to 
      metabolize drugs, and a worsening of the metabolic dysregulation identified in 
      young mice. Our study reveals that while the regulatory function of CMA cannot be 
      compensated for in young organisms, its contribution to protein homeostasis can 
      be handled by other proteolytic systems. However, the decline in the compensatory 
      ability identified with age explains the more severe consequences of CMA 
      impairment in older organisms and the contribution of CMA malfunction to the 
      gradual decline in proteostasis and stress resistance observed during aging.
CI  - (c) 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley 
      & Sons Ltd.
FAU - Schneider, Jaime L
AU  - Schneider JL
AD  - Department of Developmental and Molecular Biology, Albert Einstein College of 
      Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA; Institute for Aging 
      Studies, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 
      10461, USA.
FAU - Villarroya, Joan
AU  - Villarroya J
FAU - Diaz-Carretero, Antonio
AU  - Diaz-Carretero A
FAU - Patel, Bindi
AU  - Patel B
FAU - Urbanska, Aleksandra M
AU  - Urbanska AM
FAU - Thi, Mia M
AU  - Thi MM
FAU - Villarroya, Francesc
AU  - Villarroya F
FAU - Santambrogio, Laura
AU  - Santambrogio L
FAU - Cuervo, Ana Maria
AU  - Cuervo AM
LA  - eng
GR  - R01 AG021904/AG/NIA NIH HHS/United States
GR  - P30 DK041296/DK/NIDDK NIH HHS/United States
GR  - AG031782/AG/NIA NIH HHS/United States
GR  - R01 AG045223/AG/NIA NIH HHS/United States
GR  - P30 AG038072/AG/NIA NIH HHS/United States
GR  - F30AG046109/AG/NIA NIH HHS/United States
GR  - P01 AG031782/AG/NIA NIH HHS/United States
GR  - R01 DK091466/DK/NIDDK NIH HHS/United States
GR  - R37 AG021904/AG/NIA NIH HHS/United States
GR  - R01 AI137198/AI/NIAID NIH HHS/United States
GR  - AG038072/AG/NIA NIH HHS/United States
GR  - R01 DK098408/DK/NIDDK NIH HHS/United States
GR  - T32 GM007288/GM/NIGMS NIH HHS/United States
GR  - F30 AG046109/AG/NIA NIH HHS/United States
GR  - P30 CA013330/CA/NCI NIH HHS/United States
GR  - T32-GM007288/GM/NIGMS NIH HHS/United States
GR  - AG21904/AG/NIA NIH HHS/United States
GR  - DK098408/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150123
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Molecular Chaperones)
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Autophagy/*physiology
MH  - Homeostasis
MH  - Humans
MH  - Liver/*physiology
MH  - Lysosomes/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Chaperones/*physiology
MH  - Oxidative Stress/physiology
MH  - Protein Aggregation, Pathological
PMC - PMC4364837
OTO - NOTNLM
OT  - autophagy
OT  - lysosomal protein degradation
OT  - macroautophagy
OT  - oxidative stress
OT  - protein aggregation
OT  - proteotoxicity
OT  - ubiquitin-proteasome system
EDAT- 2015/01/27 06:00
MHDA- 2015/12/15 06:00
PMCR- 2015/04/01
CRDT- 2015/01/27 06:00
PHST- 2014/12/11 00:00 [accepted]
PHST- 2015/01/27 06:00 [entrez]
PHST- 2015/01/27 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - 10.1111/acel.12310 [doi]
PST - ppublish
SO  - Aging Cell. 2015 Apr;14(2):249-64. doi: 10.1111/acel.12310. Epub 2015 Jan 23.