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Open AccessJournal ArticleDOI

Differential Expression of Sirtuins in the Aging rat Brain

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.

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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.
Journal Article

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.

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

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.
References
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Journal ArticleDOI

A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding

TL;DR: This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr with little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose.
Journal ArticleDOI

Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan

TL;DR: The potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD+, and increases cell survival by stimulating Sirt1-dependent deacetylation of p53.
Journal ArticleDOI

Oxidative stress in neurodegeneration: cause or consequence?

TL;DR: A review of the evidence for oxidative stress in neurodegeneration and how this relates to other cellular events can be found in this article, where a growing number of in vitro and in vivo models that emulate human disease pathology is aiding scientists in deciphering just where oxidative stress intersects with other cellular processes.
Journal ArticleDOI

Sirtuins in mammals: insights into their biological function

TL;DR: The current understanding of the biological function of the seven mammalian sirtuins, SIRT1-7, is described and their potential as mediators of caloric restriction and as pharmacological targets to delay and treat human age-related diseases are discussed.
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