Numerous theories of how and why aging occurs have been postulated but a definitive comprehensive explanation remains elusive. Attempts to unravel genetic details of aging resulted in the identification of a yeast gen...Numerous theories of how and why aging occurs have been postulated but a definitive comprehensive explanation remains elusive. Attempts to unravel genetic details of aging resulted in the identification of a yeast gene known as Sir2 as a modulator of life span. Identification and characterization of mammalian Sir2 homologs followed and has catapulted aging research to exciting new levels. This review begins with basic definitions of aging and then describes some of the most common theories of the aging process. The review presents information related to the initial discovery of the Sirtuins and summarizes some of the recent advances in defining roles for Sirtuin family members. SIRT6 is discussed in greater detail because it is one of the best characterized of the mammalian Sirtuins and seems to be one of the most important in the aging process and metabolic regulation.展开更多
The quantitative induction of VIN3 by low temperatures is required for PRC2 repression of FLC and promotion of flowering （vernalization） in Arabidopsis. Histone acetylation, a chromatin modification commonly associa...The quantitative induction of VIN3 by low temperatures is required for PRC2 repression of FLC and promotion of flowering （vernalization） in Arabidopsis. Histone acetylation, a chromatin modification commonly associated with gene transcription, increased on VIN3 chromatin in two spatially and temporally distinct phases in response to low temperatures. During short-term cold exposure, histone H3 acetylation at the transcription start site rapidly increased, implying that it is required for VlN3 induction. Subsequent changes in histone H3 and H4 acetylation occurred following continued VIN3 transcription during prolonged cold exposure. Members of the SAGA-like transcriptional adaptor complex, including the histone acetyltransferase GCNS, which induces expression of the cold acclimation pathway genes, do not regulate VlN3 induction during cold exposure, indicating that the cold acclimation pathway and the cold-induction of VlN3 are regulated by different transcriptional mechanisms. Mutations in the other 11 histone acetyltransferase genes did not affect VlN3 induction. However, nicotinamide, a histone deacetyiase inhibitor, induced VIN3 and altered histone acetylation at the VIN3 locus. VIN3 induction was proportional to the length of nicotinamide treatment, which was associated with an early-flowering phenotype and repression of FLC. However, unlike vernalization, the repression of FLC was independent of VIN3 activity. Nicotinamide treatment did not cause a change in the expression of any genes in the autonomous pathway or members of the PRC2 complex, the well characterized repressors of FLC. Our data suggest that FLC is repressed via a novel pathway involving the SIR2 class of histone deacetylases.展开更多
DNA的大部分区域通过包装成特殊的染色质结构而失去活性称为染色质沉默。这些特殊的染色质结构在维持染色体结构稳定和基因调控中起重要作用。有实验表明,沉默染色质的组蛋白H3和H4的的氨基末端尾部相对于基因组的其他区域是低乙酰化的...DNA的大部分区域通过包装成特殊的染色质结构而失去活性称为染色质沉默。这些特殊的染色质结构在维持染色体结构稳定和基因调控中起重要作用。有实验表明,沉默染色质的组蛋白H3和H4的的氨基末端尾部相对于基因组的其他区域是低乙酰化的。组蛋白去乙酰化酶SIR2(silent information regulator2)是参与染色质沉默的一种重要的蛋白质。SIR2具有两种相关联的酶活性,组蛋白去乙酰化酶活性和NAD高能骨架的断裂活性,并在酶反应过程中产生一种新的产物氧代乙酰基ADP核糖基(O-acetyl-ADP-ribose)。SIR2的组蛋白去乙酰化酶活性为研究SIR2与沉默染色质的组蛋白低乙酰化状态的关系提供了直接证据。而SIR2的这两种酶活性的关系也表明,组蛋白去乙酰化酶活性不是SIR2惟一的功能。SIR2的NAD水解酶活性和O-acetyl-ADP-ribose的合成过程也可能是染色质沉默机制所必需的。展开更多
Mammalian Sirtuins are the homologs of yeast Saccharo myces cerevisiae Sir2 （silent information regulator 2） which functions in chromatin silencing to prevent genomi~ instability and aging by catalyzing the histone ...Mammalian Sirtuins are the homologs of yeast Saccharo myces cerevisiae Sir2 （silent information regulator 2） which functions in chromatin silencing to prevent genomi~ instability and aging by catalyzing the histone deacetyl ation [1]. There are seven members in Sirtuin famil, （SIRT1-SIRT7）. They all contain evolutionary conservel enzymatic domain which is nicotinamide adenine dinucleo tide （NAD）-dependent histone deacetylase that targets wide variety of histone or non-histone proteins for biologiq cal functions. Each of the Sirtuins has distinctive function~ / and cellular localization. SIRT1, 6 ＆ 7 are localized in nut cleus, and SIRT2 is localized at cytoplasm while SIRT3, ＆ 5 are localized in mitochondria [2]. ｜展开更多
Resveratrol(RES),a natural polyphenolic phytochemical,has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer’s disease(AD)by the activation of sirtuin 1(Sirt1/Sir2).In this...Resveratrol(RES),a natural polyphenolic phytochemical,has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer’s disease(AD)by the activation of sirtuin 1(Sirt1/Sir2).In this study,we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein(APP),whose duplications and mutations cause familial AD.We found a mild but significant transcriptional increase of Drosophila Sir2(dSir2)by RES supplementation for up to 17 days in APP flies,but not for 7 days.RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies.We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons.Interestingly,RES increased sleep in the absence of dSir2 in dSir2-null mutants,and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies.Finally,we showed that Aβaggregates in APP flies were reduced by RES and dSir2,probably via inhibiting Drosophilaβ-secretase(dBACE).Our data suggest that RES rescues the APP-induced behavioral deficits and Aβburden largely,but not exclusively,via dSir2.展开更多
文摘Numerous theories of how and why aging occurs have been postulated but a definitive comprehensive explanation remains elusive. Attempts to unravel genetic details of aging resulted in the identification of a yeast gene known as Sir2 as a modulator of life span. Identification and characterization of mammalian Sir2 homologs followed and has catapulted aging research to exciting new levels. This review begins with basic definitions of aging and then describes some of the most common theories of the aging process. The review presents information related to the initial discovery of the Sirtuins and summarizes some of the recent advances in defining roles for Sirtuin family members. SIRT6 is discussed in greater detail because it is one of the best characterized of the mammalian Sirtuins and seems to be one of the most important in the aging process and metabolic regulation.
文摘The quantitative induction of VIN3 by low temperatures is required for PRC2 repression of FLC and promotion of flowering （vernalization） in Arabidopsis. Histone acetylation, a chromatin modification commonly associated with gene transcription, increased on VIN3 chromatin in two spatially and temporally distinct phases in response to low temperatures. During short-term cold exposure, histone H3 acetylation at the transcription start site rapidly increased, implying that it is required for VlN3 induction. Subsequent changes in histone H3 and H4 acetylation occurred following continued VIN3 transcription during prolonged cold exposure. Members of the SAGA-like transcriptional adaptor complex, including the histone acetyltransferase GCNS, which induces expression of the cold acclimation pathway genes, do not regulate VlN3 induction during cold exposure, indicating that the cold acclimation pathway and the cold-induction of VlN3 are regulated by different transcriptional mechanisms. Mutations in the other 11 histone acetyltransferase genes did not affect VlN3 induction. However, nicotinamide, a histone deacetyiase inhibitor, induced VIN3 and altered histone acetylation at the VIN3 locus. VIN3 induction was proportional to the length of nicotinamide treatment, which was associated with an early-flowering phenotype and repression of FLC. However, unlike vernalization, the repression of FLC was independent of VIN3 activity. Nicotinamide treatment did not cause a change in the expression of any genes in the autonomous pathway or members of the PRC2 complex, the well characterized repressors of FLC. Our data suggest that FLC is repressed via a novel pathway involving the SIR2 class of histone deacetylases.
文摘DNA的大部分区域通过包装成特殊的染色质结构而失去活性称为染色质沉默。这些特殊的染色质结构在维持染色体结构稳定和基因调控中起重要作用。有实验表明,沉默染色质的组蛋白H3和H4的的氨基末端尾部相对于基因组的其他区域是低乙酰化的。组蛋白去乙酰化酶SIR2(silent information regulator2)是参与染色质沉默的一种重要的蛋白质。SIR2具有两种相关联的酶活性,组蛋白去乙酰化酶活性和NAD高能骨架的断裂活性,并在酶反应过程中产生一种新的产物氧代乙酰基ADP核糖基(O-acetyl-ADP-ribose)。SIR2的组蛋白去乙酰化酶活性为研究SIR2与沉默染色质的组蛋白低乙酰化状态的关系提供了直接证据。而SIR2的这两种酶活性的关系也表明,组蛋白去乙酰化酶活性不是SIR2惟一的功能。SIR2的NAD水解酶活性和O-acetyl-ADP-ribose的合成过程也可能是染色质沉默机制所必需的。
文摘Mammalian Sirtuins are the homologs of yeast Saccharo myces cerevisiae Sir2 （silent information regulator 2） which functions in chromatin silencing to prevent genomi~ instability and aging by catalyzing the histone deacetyl ation [1]. There are seven members in Sirtuin famil, （SIRT1-SIRT7）. They all contain evolutionary conservel enzymatic domain which is nicotinamide adenine dinucleo tide （NAD）-dependent histone deacetylase that targets wide variety of histone or non-histone proteins for biologiq cal functions. Each of the Sirtuins has distinctive function~ / and cellular localization. SIRT1, 6 ＆ 7 are localized in nut cleus, and SIRT2 is localized at cytoplasm while SIRT3, ＆ 5 are localized in mitochondria [2]. ｜
基金funded by grants from the National Natural Science Foundation of China(81970999)the Shanghai Rising-Star Program(19QA1404900)the Innovation Program of the Shanghai Municipal Education Commission(2019-01-07-00-02-E00037).
文摘Resveratrol(RES),a natural polyphenolic phytochemical,has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer’s disease(AD)by the activation of sirtuin 1(Sirt1/Sir2).In this study,we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein(APP),whose duplications and mutations cause familial AD.We found a mild but significant transcriptional increase of Drosophila Sir2(dSir2)by RES supplementation for up to 17 days in APP flies,but not for 7 days.RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies.We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons.Interestingly,RES increased sleep in the absence of dSir2 in dSir2-null mutants,and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies.Finally,we showed that Aβaggregates in APP flies were reduced by RES and dSir2,probably via inhibiting Drosophilaβ-secretase(dBACE).Our data suggest that RES rescues the APP-induced behavioral deficits and Aβburden largely,but not exclusively,via dSir2.
