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SIRTain regulators of premature senescence and accelerated aging.

Ghosh S, Zhou Z - Protein Cell (2015)

Bottom Line: Amongst the seven known mammalian sirtuin proteins, SIRT1 has gained much attention due to its widely acknowledged roles in promoting longevity and ameliorating age-associated pathologies.The roles of sirtuins in various cellular processes have been extrapolated to draw inter-linkage with anti-aging mechanisms.Also, the latest findings on sirtuins which might have potential effects in the process of aging have been reviewed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, The University of Hong Kong, Hong Kong, China.

ABSTRACT
The sirtuin proteins constitute class III histone deacetylases (HDACs). These evolutionarily conserved NAD(+)-dependent enzymes form an important component in a variety of cellular and biological processes with highly divergent as well as convergent roles in maintaining metabolic homeostasis, safeguarding genomic integrity, regulating cancer metabolism and also inflammatory responses. Amongst the seven known mammalian sirtuin proteins, SIRT1 has gained much attention due to its widely acknowledged roles in promoting longevity and ameliorating age-associated pathologies. The contributions of other sirtuins in the field of aging are also gradually emerging. Here, we summarize some of the recent discoveries in sirtuins biology which clearly implicate the functions of sirtuin proteins in the regulation of premature cellular senescence and accelerated aging. The roles of sirtuins in various cellular processes have been extrapolated to draw inter-linkage with anti-aging mechanisms. Also, the latest findings on sirtuins which might have potential effects in the process of aging have been reviewed.

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Related in: MedlinePlus

Schematic representation showing the regulation of premature aging by sirtuins via multiple biological processes
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Fig1: Schematic representation showing the regulation of premature aging by sirtuins via multiple biological processes

Mentions: The phenomenon of premature aging has intrigued researchers all over the globe. Given that the primary motive of nearly all biomedical research is to promote healthspan of individuals or target diseases to improve health of patients, study of the aging process and other pathologies associated with it has ignited huge interest in dissecting the molecular pathways contributing to this process. In this scenario, premature aging disorders in humans and the various animal model systems recapitulating the phenotypes of accelerated aging and cellular senescence constitute a major area of interest in understanding the intricacies of the process of aging. The field of premature aging has garnered immense interest also because of the emerging number of premature aging disorders observed in humans, with a significant proportion of the syndromes originating from mutations in particular genes. For example, laminopathy-based premature aging syndromes (collectively known as laminopathies) originate from mutations in the LMNA gene or ZMPSTE24 gene (Schreiber and Kennedy, 2013). Also, mutation or deletion of genes involved in DNA damage repair or chromatin remodeling, result in premature aging phenotypes (Ghosh and Zhou, 2014). In this regard, the silent information regulator proteins (SIRT) or the sirtuins have displayed intricate roles in promoting anti-aging effects via modulation of a spectrum of biological processes ranging from genomic maintenance, metabolic regulation, tumor suppression, inflammation and others (Fig. 1) (Choi and Mostoslavsky 2014). The sirtuins are evolutionarily conserved NAD+-dependent deacylases and ADP-ribosyltransferases (Saunders and Verdin 2007). In mammals, seven sirtuin proteins (SIRT1–7) have been identified as of now with conserved central catalytic core domains flanked by differing amino and carboxyl termini, which confer individuality to the seven sirtuins in terms of structure, cellular localization and functioning (Saunders and Verdin 2007). In this review, we have analyzed the varying roles of sirtuins with implications in the process of premature cellular senescence and accelerated aging.Figure 1


SIRTain regulators of premature senescence and accelerated aging.

Ghosh S, Zhou Z - Protein Cell (2015)

Schematic representation showing the regulation of premature aging by sirtuins via multiple biological processes
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4417679&req=5

Fig1: Schematic representation showing the regulation of premature aging by sirtuins via multiple biological processes
Mentions: The phenomenon of premature aging has intrigued researchers all over the globe. Given that the primary motive of nearly all biomedical research is to promote healthspan of individuals or target diseases to improve health of patients, study of the aging process and other pathologies associated with it has ignited huge interest in dissecting the molecular pathways contributing to this process. In this scenario, premature aging disorders in humans and the various animal model systems recapitulating the phenotypes of accelerated aging and cellular senescence constitute a major area of interest in understanding the intricacies of the process of aging. The field of premature aging has garnered immense interest also because of the emerging number of premature aging disorders observed in humans, with a significant proportion of the syndromes originating from mutations in particular genes. For example, laminopathy-based premature aging syndromes (collectively known as laminopathies) originate from mutations in the LMNA gene or ZMPSTE24 gene (Schreiber and Kennedy, 2013). Also, mutation or deletion of genes involved in DNA damage repair or chromatin remodeling, result in premature aging phenotypes (Ghosh and Zhou, 2014). In this regard, the silent information regulator proteins (SIRT) or the sirtuins have displayed intricate roles in promoting anti-aging effects via modulation of a spectrum of biological processes ranging from genomic maintenance, metabolic regulation, tumor suppression, inflammation and others (Fig. 1) (Choi and Mostoslavsky 2014). The sirtuins are evolutionarily conserved NAD+-dependent deacylases and ADP-ribosyltransferases (Saunders and Verdin 2007). In mammals, seven sirtuin proteins (SIRT1–7) have been identified as of now with conserved central catalytic core domains flanked by differing amino and carboxyl termini, which confer individuality to the seven sirtuins in terms of structure, cellular localization and functioning (Saunders and Verdin 2007). In this review, we have analyzed the varying roles of sirtuins with implications in the process of premature cellular senescence and accelerated aging.Figure 1

Bottom Line: Amongst the seven known mammalian sirtuin proteins, SIRT1 has gained much attention due to its widely acknowledged roles in promoting longevity and ameliorating age-associated pathologies.The roles of sirtuins in various cellular processes have been extrapolated to draw inter-linkage with anti-aging mechanisms.Also, the latest findings on sirtuins which might have potential effects in the process of aging have been reviewed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, The University of Hong Kong, Hong Kong, China.

ABSTRACT
The sirtuin proteins constitute class III histone deacetylases (HDACs). These evolutionarily conserved NAD(+)-dependent enzymes form an important component in a variety of cellular and biological processes with highly divergent as well as convergent roles in maintaining metabolic homeostasis, safeguarding genomic integrity, regulating cancer metabolism and also inflammatory responses. Amongst the seven known mammalian sirtuin proteins, SIRT1 has gained much attention due to its widely acknowledged roles in promoting longevity and ameliorating age-associated pathologies. The contributions of other sirtuins in the field of aging are also gradually emerging. Here, we summarize some of the recent discoveries in sirtuins biology which clearly implicate the functions of sirtuin proteins in the regulation of premature cellular senescence and accelerated aging. The roles of sirtuins in various cellular processes have been extrapolated to draw inter-linkage with anti-aging mechanisms. Also, the latest findings on sirtuins which might have potential effects in the process of aging have been reviewed.

Show MeSH
Related in: MedlinePlus