PMID- 24046746
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140310
LR  - 20220311
IS  - 1663-4365 (Print)
IS  - 1663-4365 (Electronic)
IS  - 1663-4365 (Linking)
VI  - 5
DP  - 2013 Sep 6
TI  - Forever young: SIRT3 a shield against mitochondrial meltdown, aging, and 
      neurodegeneration.
PG  - 48
LID - 10.3389/fnagi.2013.00048 [doi]
LID - 48
AB  - Caloric restriction (CR), fasting, and exercise have long been recognized for 
      their neuroprotective and lifespan-extending properties; however, the underlying 
      mechanisms of these phenomena remain elusive. Such extraordinary benefits might 
      be linked to the activation of sirtuins. In mammals, the sirtuin family has seven 
      members (SIRT1-7), which diverge in tissue distribution, subcellular 
      localization, enzymatic activity, and targets. SIRT1, SIRT2, and SIRT3 have 
      deacetylase activity. Their dependence on NAD(+) directly links their activity to 
      the metabolic status of the cell. High NAD(+) levels convey neuroprotective 
      effects, possibly via activation of sirtuin family members. Mitochondrial sirtuin 
      3 (SIRT3) has received much attention for its role in metabolism and aging. 
      Specific small nucleotide polymorphisms in Sirt3 are linked to increased human 
      lifespan. SIRT3 mediates the adaptation of increased energy demand during CR, 
      fasting, and exercise to increased production of energy equivalents. SIRT3 
      deacetylates and activates mitochondrial enzymes involved in fatty acid 
      beta-oxidation, amino acid metabolism, the electron transport chain, and antioxidant 
      defenses. As a result, the mitochondrial energy metabolism increases. In 
      addition, SIRT3 prevents apoptosis by lowering reactive oxygen species and 
      inhibiting components of the mitochondrial permeability transition pore. 
      Mitochondrial deficits associated with aging and neurodegeneration might 
      therefore be slowed or even prevented by SIRT3 activation. In addition, 
      upregulating SIRT3 activity by dietary supplementation of sirtuin activating 
      compounds might promote the beneficial effects of this enzyme. The goal of this 
      review is to summarize emerging data supporting a neuroprotective action of SIRT3 
      against Alzheimer's disease, Huntington's disease, Parkinson's disease, and 
      amyotrophic lateral sclerosis.
FAU - Kincaid, Brad
AU  - Kincaid B
AD  - Burnett School of Biomedical Sciences, College of Medicine, University of Central 
      Florida Orlando, FL, USA.
FAU - Bossy-Wetzel, Ella
AU  - Bossy-Wetzel E
LA  - eng
GR  - R01 EY016164/EY/NEI NIH HHS/United States
GR  - R01 NS055193/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20130906
PL  - Switzerland
TA  - Front Aging Neurosci
JT  - Frontiers in aging neuroscience
JID - 101525824
PMC - PMC3764375
OTO - NOTNLM
OT  - SIRT3
OT  - aging
OT  - antioxidants
OT  - caloric restriction
OT  - mitochondria
OT  - neurodegeneration
OT  - neuroprotection
EDAT- 2013/09/21 06:00
MHDA- 2013/09/21 06:01
PMCR- 2013/01/01
CRDT- 2013/09/19 06:00
PHST- 2013/06/04 00:00 [received]
PHST- 2013/08/21 00:00 [accepted]
PHST- 2013/09/19 06:00 [entrez]
PHST- 2013/09/21 06:00 [pubmed]
PHST- 2013/09/21 06:01 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.3389/fnagi.2013.00048 [doi]
PST - epublish
SO  - Front Aging Neurosci. 2013 Sep 6;5:48. doi: 10.3389/fnagi.2013.00048.