Aging and disease: connections to sirtuins

Dönmez, Gizem; Guarente, Leonard

doi:10.1111/j.1474-9726.2010.00548.x

Cited by 290 publications

(223 citation statements)

References 52 publications

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“…Meanwhile, Sirtuins were shown to promote longevity in diverse organisms and their pathways could affect diseases of aging in mammals, including neurodegenerative diseases, stress responses, diabetes, and cancer (Gan and Mucke, 2008;Donmez and Guarente, 2010). Sirt1 plays important roles in the response to metabolism, longevity, and aging (Engel and Mahlknecht, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Mammals contain seven homologs of yeast Sir2 (Sirtuins, Sirt1-7), which are categorized by their highly conserved central NAD + -binding and catalytic domain and also by unique additional N-terminal and/or C-terminal sequences of variable length (Haigis and Guarente, 2006;Michan and Sinclair, 2007). Like Sir2, the mammal Sirtuins also play important roles in a variety of biological processes, including metabolism (Rodgers et al, 2005;Lomb et al, 2010), apoptosis (Verdin et al, 2010;Kyrylenko and Baniahmad, 2010), oxidative stress and cytokine responses (Kubota et al, 2009) and further influencing aging (Donmez and Guarente, 2010;Haigis and Sinclair, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Effect of breed on the expression of Sirtuins (Sirt1-7) and antioxidant capacity in porcine brain

Ren

Shan

Zhu

et al. 2013

Animal

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Sirtuins, NAD-dependent histone deacetylase (HDAC), are correlated to aging and antioxidant. The aim of this study was to determine breed differences of porcine Sirtuins expression and antioxidant capacity in brain between Jinhua pigs (a fatty breed of China) and Danish Landrace pigs (a leaner breed). Effect of age on Sirtuins' expression was also investigated. At the age of 180 days, the mRNA levels of Sirt1, as well as Sirt2 and Sirt4, in Jinhua pigs were greater, but the mRNA levels of Sirt3, Sirt5, Sirt6, and Sirt7 of Jinhua pigs were lower compared with Danish Landrace pigs. Likewise, at the same BW of 64 kg, the mRNA levels of Sirtuins, except Sirt5 and Sirt7, in Jinhua pigs were greater than Danish Landrace pigs. Meanwhile, Jinhua pigs possessed higher antioxidants activity than Danish Landrace pigs either at the same age or at the same BW. Furthermore, mRNA levels of Sirtuins were decreased with age in brain of the two breeds from 30 to 120 days. The results indicated that Sirtuins expression in brain was different between fatty and lean pigs, and Sirtuins expression may be correlated to antioxidant capacity. In addition, age could down-regulate Siruins expression in porcine brain.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of breed on the expression of Sirtuins (Sirt1-7) and antioxidant capacity in porcine brain

Ren

Shan

Zhu

et al. 2013

Animal

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“…Sirtuins (SIRTs 1‐7) are protein deacetylases/ADP ribosyltransferases involved in various biological functions (Donmez & Guarente, 2010; Saunders & Verdin, 2009). They can be divided into nuclear (SIRT1, SIRT6, and SIRT7), mitochondrial (SIRT3, SIRT4, and SIRT5), and cytosolic (SIRT2) forms, although this division is not unconditional and some sirtuins are detected in more than one cell compartment (Michishita, Park, Burneskis, Barrett, & Horikawa, 2005).…”

Section: Introductionmentioning

confidence: 99%

SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation

Zeng

Jiang²,

et al. 2018

Aging Cell

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SIRT4 modulates energy homeostasis in multiple cell types and tissues. However, its role in meiotic oocytes remains unknown. Here, we report that mouse oocytes overexpressing SIRT4 are unable to completely progress through meiosis, showing the inadequate mitochondrial redistribution, lowered ATP content, elevated reactive oxygen species (ROS) level, with the severely disrupted spindle/chromosome organization. Moreover, we find that phosphorylation of Ser293‐PDHE1α mediates the effects of SIRT4 overexpression on metabolic activity and meiotic events in oocytes by performing functional rescue experiments. By chance, we discover the SIRT4 upregulation in oocytes from aged mice; and importantly, the maternal age‐associated deficient phenotypes in oocytes can be partly rescued through the knockdown of SIRT4. These findings reveal the critical role for SIRT4 in the control of energy metabolism and meiotic apparatus during oocyte maturation and indicate that SIRT4 is an essential factor determining oocyte quality.

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“…As we observed a marked decrease in the amount of H3K9-Ac and H4K16-Ac, both of which are substrates for the type III family of HDACs known as sirtuins, we decided to determine whether Sirt1, a member of the sirtuin family and responsible for the formation of facultative heterochromatin, was recruited to these promoters (38,40). Although we detected only background levels of Sirt1 on this promoter in WT and XP-D cells, XP-D/CS cells displayed increased levels of Sirt1 recruited to these promoters (Fig.…”

Section: Xp-d/cs Cells Elicit Transcriptional Stress Response Upon Uvmentioning

confidence: 99%

Sirt1 suppresses RNA synthesis after UV irradiation in combined xeroderma pigmentosum group D/Cockayne syndrome (XP-D/CS) cells

Vélez-Cruz

Zadorin

Coin

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Specific mutations in the XPD subunit of transcription factor IIH result in combined xeroderma pigmentosum (XP)/Cockayne syndrome (CS), a severe DNA repair disorder characterized at the cellular level by a transcriptional arrest following UV irradiation. This transcriptional arrest has always been thought to be the result of faulty transcription-coupled repair. In the present study, we showed that, following UV irradiation, XP-D/CS cells displayed a gross transcriptional dysregulation compared with "pure" XP-D cells or WT cells. Furthermore, global RNA-sequencing analysis showed that XP-D/CS cells repressed the majority of genes after UV, whereas pure XP-D cells did not. By using housekeeping genes as a model, we demonstrated that XP-D/CS cells were unable to reassemble these gene promoters and thus to restart transcription after UV irradiation. Furthermore, we found that the repression of these promoters in XP-D/CS cells was not a simple consequence of deficient repair but rather an active heterochromatinization process mediated by the histone deacetylase Sirt1. Indeed, RNA-sequencing analysis showed that inhibition of and/or silencing of Sirt1 changed the chromatin environment at these promoters and restored the transcription of a large portion of the repressed genes in XP-D/CS cells after UV irradiation. Our work demonstrates that a significant part of the transcriptional arrest displayed by XP-D/CS cells arises as a result of an active repression process and not simply as a result of a DNA repair deficiency. This dysregulation of Sirt1 function that results in transcriptional repression may be the cause of various severe clinical features in patients with XP-D/ CS that cannot be explained by a DNA repair defect.nucleotide excision repair | sirtuins | aging | progeria

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Aging and disease: connections to sirtuins

Cited by 290 publications

References 52 publications

Effect of breed on the expression of Sirtuins (Sirt1-7) and antioxidant capacity in porcine brain

Effect of breed on the expression of Sirtuins (Sirt1-7) and antioxidant capacity in porcine brain

SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation

Sirt1 suppresses RNA synthesis after UV irradiation in combined xeroderma pigmentosum group D/Cockayne syndrome (XP-D/CS) cells

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