PMID- 21094524
OWN - NLM
STAT- MEDLINE
DCOM- 20101230
LR  - 20221109
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 143
IP  - 5
DP  - 2010 Nov 24
TI  - Sirt3 mediates reduction of oxidative damage and prevention of age-related 
      hearing loss under caloric restriction.
PG  - 802-12
LID - 10.1016/j.cell.2010.10.002 [doi]
AB  - Caloric restriction (CR) extends the life span and health span of a variety of 
      species and slows the progression of age-related hearing loss (AHL), a common 
      age-related disorder associated with oxidative stress. Here, we report that CR 
      reduces oxidative DNA damage in multiple tissues and prevents AHL in wild-type 
      mice but fails to modify these phenotypes in mice lacking the mitochondrial 
      deacetylase Sirt3, a member of the sirtuin family. In response to CR, Sirt3 
      directly deacetylates and activates mitochondrial isocitrate dehydrogenase 2 
      (Idh2), leading to increased NADPH levels and an increased ratio of 
      reduced-to-oxidized glutathione in mitochondria. In cultured cells, 
      overexpression of Sirt3 and/or Idh2 increases NADPH levels and protects from 
      oxidative stress-induced cell death. Therefore, our findings identify Sirt3 as an 
      essential player in enhancing the mitochondrial glutathione antioxidant defense 
      system during CR and suggest that Sirt3-dependent mitochondrial adaptations may 
      be a central mechanism of aging retardation in mammals.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Someya, Shinichi
AU  - Someya S
AD  - Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, 
      53706, USA.
FAU - Yu, Wei
AU  - Yu W
FAU - Hallows, William C
AU  - Hallows WC
FAU - Xu, Jinze
AU  - Xu J
FAU - Vann, James M
AU  - Vann JM
FAU - Leeuwenburgh, Christiaan
AU  - Leeuwenburgh C
FAU - Tanokura, Masaru
AU  - Tanokura M
FAU - Denu, John M
AU  - Denu JM
FAU - Prolla, Tomas A
AU  - Prolla TA
LA  - eng
GR  - R01 AG021905-01/AG/NIA NIH HHS/United States
GR  - R01 AG021905-04/AG/NIA NIH HHS/United States
GR  - R01 AG021905-05/AG/NIA NIH HHS/United States
GR  - R01 AG021905-02/AG/NIA NIH HHS/United States
GR  - GM065386/GM/NIGMS NIH HHS/United States
GR  - AG021905/AG/NIA NIH HHS/United States
GR  - R01 GM065386-09/GM/NIGMS NIH HHS/United States
GR  - R01 GM065386/GM/NIGMS NIH HHS/United States
GR  - P30 AG028740/AG/NIA NIH HHS/United States
GR  - R01 AG021905-03/AG/NIA NIH HHS/United States
GR  - R01 AG021905/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Antioxidants)
RN  - 0 (Sirt3 protein, mouse)
RN  - EC 1.1.1.41 (Isocitrate Dehydrogenase)
RN  - EC 3.5.1.- (Sirtuin 3)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
CIN - Cell. 2010 Nov 24;143(5):667-8. PMID: 21111225
CIN - Nat Rev Mol Cell Biol. 2012 Apr;13(4):207. PMID: 22374145
MH  - Aging/*metabolism
MH  - Animals
MH  - Antioxidants/metabolism
MH  - *Caloric Restriction
MH  - DNA Damage
MH  - Female
MH  - Glutathione/metabolism
MH  - Hearing Loss/*prevention & control
MH  - Isocitrate Dehydrogenase/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/*metabolism
MH  - *Oxidative Stress
MH  - Sirtuin 3/genetics/*metabolism
PMC - PMC3018849
MID - NIHMS244038
EDAT- 2010/11/26 06:00
MHDA- 2010/12/31 06:00
PMCR- 2011/11/24
CRDT- 2010/11/25 06:00
PHST- 2010/07/19 00:00 [received]
PHST- 2010/09/03 00:00 [revised]
PHST- 2010/09/30 00:00 [accepted]
PHST- 2010/11/25 06:00 [entrez]
PHST- 2010/11/26 06:00 [pubmed]
PHST- 2010/12/31 06:00 [medline]
PHST- 2011/11/24 00:00 [pmc-release]
AID - S0092-8674(10)01138-4 [pii]
AID - 10.1016/j.cell.2010.10.002 [doi]
PST - ppublish
SO  - Cell. 2010 Nov 24;143(5):802-12. doi: 10.1016/j.cell.2010.10.002.