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Silent mating type information regulator 2-related enzymes or sirtuin family proteins are nicotinamide adenine dinucleotide (NAD
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A number of research has shown that the plant polyphenol resveratrol,one of the most prominent small molecules,has beneficial protective effects in multiple organisms,including worms,flies,and killifish.To understand the effects of resveratrol on lifespan,we evaluated its effects in the silkworm Bombyx mori.In this study,we found that lifespan was significantly prolonged in both female and male silkworms treated with resveratrol.Silkworm larval weight was significantly increased from day 3 of the 5th larval instar(L5D3) to day 7 of the 5th larval instar (L5D7).However,the weight of the pupa,cocoon,and total cocoon was not significantly different in female silkworms with resveratrol treatment than that in controls.Meanwhile,resveratrol significantly improved the thermotolerance of the silkworms,which enhanced their survival rate.Moreover,antioxidant activity was increased by resveratrol in both female and male silkworms.Furthermore,an antioxidant-related signalling pathway,SIRT7-FoxO-GST,was activated in silkworms with resveratrol treatment.Collectively,these results help us to understand the molecular pathways underlying resveratrol induced pro-longevity effects and indicate that silkworm is a promising animal model for evaluating the effects of lifespan-extending drugs.
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SIRT7, a sirtuin family member implicated in aging and disease, is a regulator of metabolism and stress responses. It remains elusive how human somatic stem cell populations might be impacted by SIRT7. Here, we found that SIRT7 expression declines during human mesenchymal stem cell (hMSC) aging and that SIRT7 deficiency accelerates senescence. Mechanistically, SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins, thus maintaining the repressive state of heterochromatin at nuclear periphery. Accordingly, deficiency of SIRT7 results in loss of heterochromatin, de-repression of the LINE1 retrotransposon (LINE1), and activation of innate immune signaling via the cGAS-STING pathway. These aging-associated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor. Together, these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.
RESUMEN
SIRT7, a sirtuin family member implicated in aging and disease, is a regulator of metabolism and stress responses. It remains elusive how human somatic stem cell populations might be impacted by SIRT7. Here, we found that SIRT7 expression declines during human mesenchymal stem cell (hMSC) aging and that SIRT7 deficiency accelerates senescence. Mechanistically, SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins, thus maintaining the repressive state of heterochromatin at nuclear periphery. Accordingly, deficiency of SIRT7 results in loss of heterochromatin, de-repression of the LINE1 retrotransposon (LINE1), and activation of innate immune signaling via the cGAS-STING pathway. These aging-associated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor. Together, these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.
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As a member of the Sirtuins family in mammals, SIRT7 locates in nucleus and is a highly specific H3K18Ac (acetylated lysine 18 of histone H3) deacetylase. Recent studies showed that SIRT7 could participate in the ribosomal RNA transcription, cell metabolism, cell stress and DNA damage repair through various signaling pathways. In addition, SIRT7 is also closely related with aging, heart disease and fatty liver. In particular, SIRT7 plays important roles in the regulation of initiation and development of various tumors, such as liver cancer, gastric cancer, breast cancer, bladder cancer, colorectal cancer, and head/neck squamous cell carcinoma. This review describes the cellular and molecular functions of SIRT7, and systematically summarizes recent progress of SIRT7 in human disease.
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Animales , Humanos , Histonas , Lisina , Neoplasias , Transducción de Señal , Sirtuinas , MetabolismoRESUMEN
Objective:To investigate the effects of SIRT7 on acute liver injury induced by lipopolysaccharide (LPS) or D-galactosamine (D-GalN)/LPS and its mechanisms. Methods:Thirteen-week-old C57BL/6J mice were randomly divided into normal saline group (n=5), LPS group (n=7), and D-GalN/LPS group (n=8), which were respectively intraperitoneally injected with normal saline, LPS or D-GalN/LPS. The serum and livers of normal saline group and LPS group mice were collected 24 hours after the injection, and the samples of D-GalN/LPS group were collected 8 hours after the injection. Liver pathological changes were compared by using H-E staining, and serological indicators of the mice from three groups were also compared. Liver apoptosis and inflammatory cells infiltration were determined by TUNEL staining and F4/80 staining. Meanwhile, the mRNA levels of SIRT7 and inflammatory factors, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α) in livers were detected by realtime-PCR. Western blotting was used to detect the protein levels of SIRT7, cleaved-caspase3 and the 78 kDa glucose regulated protein (GRP78) in mouse liver tissues. AML-12 cell line overexpressing SIRT7 was stimulated with LPS, and Western blotting was used to study the roles of SIRT7 in the endoplasmic reticulum (ER) stress induced by LPS in vitro. Results:LPS or D-GalN/LPS induced inflammatory cells infiltration, hyperemia and hepatocytes apoptosis in livers. Meanwhile, serum glutamic-pyruvic transaminase (GPT) and glutamic-oxalacetic transaminase (GOT) in the mice treated by LPS or D-GalN/LPS were significantly increased. Moreover, both liver SIRT7 mRNA and protein levels were down-regulated, while GRP78 protein in ER stress pathway was up-regulated. In AML-12 cells, SIRT7 overexpression inhibited LPS-induced up-regulation of GRP78. Conclusion:SIRT7 protects against LPS or D-GalN/LPS-induced hepatocytes apoptosis by attenuating ER stress via inactivating GRP78.