Recent progress in the biology and physiology of Sirtuins

Translational Medicine Branch, National Heart Lung and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature (Impact Factor: 41.46). 08/2009; 460(7255):587-91. DOI: 10.1038/nature08197
Source: PubMed


The sirtuins are a highly conserved family of NAD(+)-dependent enzymes that regulate lifespan in lower organisms. Recently, the mammalian sirtuins have been connected to an ever widening circle of activities that encompass cellular stress resistance, genomic stability, tumorigenesis and energy metabolism. Here we review the recent progress in sirtuin biology, the role these proteins have in various age-related diseases and the tantalizing notion that the activity of this family of enzymes somehow regulates how long we live.

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Available from: Raul Mostoslavsky, Apr 19, 2014
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    • "SIRT1 regulates insulin sensitivity, metabolism , and mitochondrial biogenesis through deacetylation of PGC-1α (Finkel, Deng, & Mostoslavsky, 2009). SIRT1 modulates the expression of several genes involved in lipid metabolism (Finkel et al., 2009), however, no data are available comparing skeletal muscle SIRT1 protein content in men and women. "
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    ABSTRACT: This study was designed to investigate the association of gender, fibre type composition, and anaerobic performance with the basal skeletal muscle signalling cascades regulating muscle phenotype. Muscle biopsies were obtained from 25 men and 10 women all young and healthy. Protein phosphorylation of Thr(172)AMPKα, Ser(221)ACCβ, Thr(286)CaMKII as well as total protein abundance of PGC-1α, SIRT1, and CnA were measured by Western blot and anaerobic performance by the Wingate test. Percent type I myosin heavy chain (MHC I) was lower in men (37.1 ± 10.4 vs. 58.5 ± 12.5, P < .01). Total, free testosterone and free androgen index were higher in men (11.5, 36.6 and 40.6 fold, respectively, P < .01). AMPKα phosphorylation was 2.2-fold higher in men compared to women (P < .01). Total Ser(221)ACCβ and Thr(286)CaMKII fractional phosphorylation tended to be higher in men (P = .1). PGC1-α and SIRT1 total protein expression was similar in men and women, whereas CnA tended to be higher in men (P = .1). Basal AMPKα phosphorylation was linearly related to the percentage of MHC I in men (r = 0.56; P < .01), but not in women. No association was observed between anaerobic performance and basal phosphorylations in men and women, analysed separately. In summary, skeletal muscle basal AMPKα phosphorylation is higher in men compared to women, with no apparent effect on anaerobic performance.
    08/2015; DOI:10.1080/17461391.2015.1063701
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    • "Another promising AD biomarker is the histone deacetylase Sirtuin 1 (Sirt1). Sirt1 is the mammalian homologue of a yeast silencing factor regulating lifespan that is involved in many cellular functions encompassing stress resistance, genomic stability, tumorigenesis, energy metabolism, and learning and memory [8]. The notion that Sirt1 is involved in AD pathological processes was derived from the discovery of reduced levels in AD human brain cortex [9]. "
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    ABSTRACT: The identification of Alzheimer's disease (AD) biomarkers is crucial to support drug discovery. Within putative biomarkers, peripheral Bdnf levels correlate with cognitive decline and AD, although conflicting findings are reported. Sirtuin 1 (Sirt1) serum levels are lower in AD patients and presenilin 1 (Psen1) is expressed by blood cells. DNA methylation is altered in AD patients, suggesting that epigenetic mechanisms play a role in AD pathophysiology. The objective of this study was to investigate promoter methylation levels of potential biomarkers in AD cases and controls. Peripheral blood DNA methylation levels were analysed by methylation-specific primer real-time PCR. Bdnf promoter methylation levels did not differ between AD patients and controls. Similarly, Sirt1 promoter revealed minimal levels of methylation which did not display significant differences between groups. No significant difference was revealed between AD patients and controls also in Psen1 methylation, showing a large variability of values among subjects. Although peripheral Bdnf expression is associated with differential promoter methylation in psychiatric and neurological disorders, our results suggest that different mechanisms take place in AD. The finding that the control of Sirt1 protein levels in blood is not exerted through the repression of mRNA expression by promoter hypermethylation is in agreement with previous data. In contrast, other studies reported that Psen1 methylation may be increased or decreased in AD patients, suggesting that additional studies are required. In conclusion, this study shows that peripheral levels of the potential AD biomarker proteins Bdnf, Sirt1, and Psen1 are not regulated by different promoter methylation. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Neuroscience Letters 08/2015; 605. DOI:10.1016/j.neulet.2015.08.012 · 2.03 Impact Factor
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    • "Interest in sirtuins grew when Sir2 was shown to slow aging in yeast mother cells (Kaeberlein et al. 1999). Many subsequent studies showed similar effects on aging, supporting the ideas of sirtuins like longevitypromoting effectors in Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and mice (Bauer et al. 2009; Berdichevsky et al. 2006; Finkel et al. 2009; Rizki et al. 2010; Rogina and Helfand 2004; Viswanathan and Guarente 2011; Viswanathan et al. 2005). Banerjee et al. (2012) demonstrated how in D. Melanogaster, overexpression of Sir2 extended the lifespan, whereas deletion of Sir2 reduces significantly the lifespan. "
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    ABSTRACT: The sirtuins comprise a highly conserved family proteins present in virtually all species from bacteria to mammals. Sirtuins are members of the highly conserved class III histone deacetylases, and seven sirtuin genes (sirtuins 1-7) have been identified and characterized in mammals. Sirtuin activity is linked to metabolic control, apoptosis, cell survival, development, inflammation, and healthy aging. In this review, we summarize and discuss the potential mutual relations between each sirtuin and cardiovascular health and the impact of sirtuins on oxidative stress and so age-related cardiovascular disorders, underlining the possibility that sirtuins will be novel targets to contrast cardiovascular risks induced by aging.
    Age 08/2015; 37(4):9804. DOI:10.1007/s11357-015-9804-y · 3.45 Impact Factor
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