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 Posted: Thu Oct 02, 2008 7:21 pm Post subject: Restoration of chaperone-mediated autophagy in aging liver i |
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Nat Med. 2008 Sep;14(9):959-65. Links
Restoration of chaperone-mediated autophagy in aging liver improves
cellular maintenance and hepatic function.Zhang C, Cuervo AM.
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.
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.
PMID: 18690243 [PubMed - in process] |
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