PMID- 18690243
OWN - NLM
STAT- MEDLINE
DCOM- 20081027
LR  - 20231213
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 14
IP  - 9
DP  - 2008 Sep
TI  - Restoration of chaperone-mediated autophagy in aging liver improves cellular 
      maintenance and hepatic function.
PG  - 959-65
LID - 10.1038/nm.1851 [doi]
AB  - Chaperone-mediated autophagy (CMA), a selective mechanism for degradation of 
      cytosolic proteins in lysosomes, contributes to the removal of altered proteins 
      as part of the cellular quality-control systems. We have previously found that 
      CMA activity declines in aged organisms and have proposed that this failure in 
      cellular clearance could contribute to the accumulation of altered proteins, the 
      abnormal cellular homeostasis and, eventually, the functional loss characteristic 
      of aged organisms. To determine whether these negative features of aging can be 
      prevented by maintaining efficient autophagic activity until late in life, in 
      this work we have corrected the CMA defect in aged rodents. We have generated a 
      double transgenic mouse model in which the amount of the lysosomal receptor for 
      CMA, previously shown to decrease in abundance with age, can be modulated. We 
      have analyzed in this model the consequences of preventing the age-dependent 
      decrease in receptor abundance in aged rodents at the cellular and organ levels. 
      We show here that CMA activity is maintained until advanced ages if the decrease 
      in the receptor abundance is prevented and that preservation of autophagic 
      activity is associated with lower intracellular accumulation of damaged proteins, 
      better ability to handle protein damage and improved organ function.
FAU - Zhang, Cong
AU  - Zhang C
AD  - Department of Developmental and Molecular Biology, Marion Bessin Liver Research 
      Center and Institute for Aging Research, 1300 Morris Park Avenue, Albert Einstein 
      College of Medicine, Bronx, New York 10461, USA.
FAU - Cuervo, Ana Maria
AU  - Cuervo AM
LA  - eng
GR  - R01 AG021904-06/AG/NIA NIH HHS/United States
GR  - P01 DK041918/DK/NIDDK NIH HHS/United States
GR  - R37 AG021904/AG/NIA NIH HHS/United States
GR  - R03 AG019834-02/AG/NIA NIH HHS/United States
GR  - AG021904/AG/NIA NIH HHS/United States
GR  - AG19834/AG/NIA NIH HHS/United States
GR  - R01 AG021904/AG/NIA NIH HHS/United States
GR  - DK041918/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (LAMP2 protein, human)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (Lysosomal Membrane Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Proteins)
RN  - 9DOW362Q29 (Zoxazolamine)
SB  - IM
CIN - Nat Med. 2008 Sep;14(9):909-10. PMID: 18776878
CIN - Hepatology. 2009 Jan;49(1):330-2. PMID: 19115216
MH  - Aging/*metabolism
MH  - Animals
MH  - Autophagy/*physiology
MH  - Gene Expression Regulation/*genetics
MH  - Humans
MH  - Liver/metabolism/*physiology/ultrastructure
MH  - Lysosomal-Associated Membrane Protein 2
MH  - Lysosomal Membrane Proteins/genetics/*metabolism
MH  - Lysosomes/metabolism
MH  - Mice
MH  - Microscopy, Electron, Transmission
MH  - Molecular Chaperones/*metabolism
MH  - Proteins/*metabolism
MH  - Zoxazolamine/pharmacokinetics
PMC - PMC2722716
MID - NIHMS101307
EDAT- 2008/08/12 09:00
MHDA- 2008/10/28 09:00
PMCR- 2009/09/01
CRDT- 2008/08/12 09:00
PHST- 2008/03/18 00:00 [received]
PHST- 2008/06/23 00:00 [accepted]
PHST- 2008/08/12 09:00 [pubmed]
PHST- 2008/10/28 09:00 [medline]
PHST- 2008/08/12 09:00 [entrez]
PHST- 2009/09/01 00:00 [pmc-release]
AID - nm.1851 [pii]
AID - 10.1038/nm.1851 [doi]
PST - ppublish
SO  - Nat Med. 2008 Sep;14(9):959-65. doi: 10.1038/nm.1851.