Differential Expression of Sirtuins in the Aging rat Brain
Nady Braidy,Anne Poljak,Ross Grant,Tharusha Jayasena,Hussein Mansour,Tailoi Chan-Ling,George A. Smythe,Perminder S. Sachdev,Gilles J. Guillemin +8 more
TLDR
It is shown that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated, and acetylation H3K9 protein expression is increased throughout the brain.Abstract:
Although there are seven mammalian sirtuins (SIRT1-7), little is known about their expression in the aging brain. To characterize the change(s) in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of "physiologically" aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy aging.read more
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Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders
TL;DR: The mechanism(s) and potential significance of interactions between SIRTs and several TFs in the regulation of cell survival and death are analyzed and a critical view is given on the application of SIRT activators/modulators in therapy of neurodegenerative diseases.
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Oxidative stress in neurodegeneration: cause or consequence?
TL;DR: The evidence for oxidative stress in neurodegeneration is reviewed and how this relates to other cellular events in the emerging roadmap leading to neurodegenesis is reviewed.
Journal ArticleDOI
Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes.
Nady Braidy,Jade Berg,James Clement,Fatemeh Khorshidi,Anne Poljak,Tharusha Jayasena,Ross Grant,Ross Grant,Ross Grant,Perminder S. Sachdev +9 more
TL;DR: Recent insights regarding the efficacy and benefits of the NAD+ precursors, nicotinamide (NAM), nicotinic acid (NA), Nicotinamide riboside (NR), and nicotinamia mononucleotide (NMN), in attenuating NAD+ decline in degenerative disease states and physiological aging are described and discussed.
Journal ArticleDOI
The brain, sirtuins, and ageing
TL;DR: The mechanisms underlying CNS regulation of the ageing process, such as microglia–neuron networks and the activities of sirtuins, a class of NAD+-dependent deacylases, are beginning to be understood and are potential targets for the prevention or treatment of age-associated dysfunction and for the extension of a healthy lifespan.
Journal ArticleDOI
Neuroprotective Functions for the Histone Deacetylase SIRT6
Shai Kaluski,Miguel Portillo,Antoine Besnard,Antoine Besnard,Daniel Stein,Monica Einav,Lei Zhong,Lei Zhong,Uwe Ueberham,Thomas Arendt,Raul Mostoslavsky,Raul Mostoslavsky,Amar Sahay,Amar Sahay,Debra Toiber +14 more
TL;DR: It is reported that brain-specific SIRT6-deficient mice survive but present behavioral defects with major learning impairments by 4 months of age and that its loss leads to toxic Tau stability and phosphorylation, suggesting that SIRT 6 and its downstream signaling could be targeted in Alzheimer's disease and age-related neurodegeneration.
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