Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan.
Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan.
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DOI：
10.3390/antiox10040572
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发表时间：
2021-04-08
期刊：
影响因子：
--
通讯作者：
Bradshaw PC
中科院分区：
文献类型：
--
作者：
Bradshaw PC
乙酰辅酶A是一种处于中枢代谢十字路口的代谢物，也是组蛋白乙酰转移酶调节基因表达的底物。在许多组织中，禁食或延长寿命的热量限制（CR）通过ATP-柠檬酸裂解酶（ACLY）降低葡萄糖衍生的代谢通量，以降低细胞质乙酰辅酶A水平，从而降低刺激促长寿自噬的p300组蛋白乙酰转移酶（HAT）的活性。因此，降低细胞质乙酰辅酶A的化合物被描述为CR模拟物。但很少有作者强调核乙酰辅酶A的潜在长寿促进作用。例如，增加核乙酰辅酶A水平增加组蛋白乙酰化，并且I类组蛋白脱乙酰酶（HDAC）抑制剂的施用通过增加组蛋白乙酰化增加寿命。因此，增加核乙酰辅酶A可能在促进长寿方面发挥重要作用。虽然细胞质乙酰辅酶A合成酶2（ACSS 2）通过减少一些外周组织中的自噬来促进衰老，但胶质AMPK活性增加或神经元分化可刺激ACSS 2核转位和染色质缔合。ACSS 2核易位可导致CREB结合蛋白（CBP）、p300/CBP相关因子（PCAF）和其他HAT的活性增加，以增加神经保护基因（包括转录因子EB（TFEB）靶基因）启动子上的组蛋白乙酰化，从而导致溶酶体生物发生和自噬增加。许多关于乙酰辅酶A代谢和衰老的知识来自酵母、果蝇和线虫的开创性研究。这些研究已经确定了组蛋白乙酰化在促进长寿中的进化保守作用。未来的研究应该集中在核乙酰辅酶A和组蛋白乙酰化在控制下丘脑炎症中的作用，下丘脑炎症是生物体衰老的重要驱动力。
Acetyl-CoA is a metabolite at the crossroads of central metabolism and the substrate of histone acetyltransferases regulating gene expression. In many tissues fasting or lifespan extending calorie restriction (CR) decreases glucose-derived metabolic flux through ATP-citrate lyase (ACLY) to reduce cytoplasmic acetyl-CoA levels to decrease activity of the p300 histone acetyltransferase (HAT) stimulating pro-longevity autophagy. Because of this, compounds that decrease cytoplasmic acetyl-CoA have been described as CR mimetics. But few authors have highlighted the potential longevity promoting roles of nuclear acetyl-CoA. For example, increasing nuclear acetyl-CoA levels increases histone acetylation and administration of class I histone deacetylase (HDAC) inhibitors increases longevity through increased histone acetylation. Therefore, increased nuclear acetyl-CoA likely plays an important role in promoting longevity. Although cytoplasmic acetyl-CoA synthetase 2 (ACSS2) promotes aging by decreasing autophagy in some peripheral tissues, increased glial AMPK activity or neuronal differentiation can stimulate ACSS2 nuclear translocation and chromatin association. ACSS2 nuclear translocation can result in increased activity of CREB binding protein (CBP), p300/CBP-associated factor (PCAF), and other HATs to increase histone acetylation on the promoter of neuroprotective genes including transcription factor EB (TFEB) target genes resulting in increased lysosomal biogenesis and autophagy. Much of what is known regarding acetyl-CoA metabolism and aging has come from pioneering studies with yeast, fruit flies, and nematodes. These studies have identified evolutionary conserved roles for histone acetylation in promoting longevity. Future studies should focus on the role of nuclear acetyl-CoA and histone acetylation in the control of hypothalamic inflammation, an important driver of organismal aging.
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影响因子：
4.2
作者：
Bhatt DP;Houdek HM;Watt JA;Rosenberger TA
通讯作者：
Rosenberger TA
DOI：
10.1177/0269881120965912
发表时间：
2021-05
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Ashok AH;Myers J;Frost G;Turton S;Gunn RN;Passchier J;Colasanti A;Marques TR;Nutt D;Lingford-Hughes A;Howes OD;Rabiner EA
通讯作者：
Rabiner EA
影响因子：
4.3
作者：
Allaman I;Bélanger M;Magistretti PJ
通讯作者：
Magistretti PJ
影响因子：
5.6
作者：
Arcidiacono OA;Krejčí J;Suchánková J;Bártová E
通讯作者：
Bártová E
DOI：
10.1073/pnas.1012851108
发表时间：
2010-12-28
影响因子：
11.1
作者：
Caccamo, Antonella;Maldonado, Monica A.;Oddo, Salvatore
通讯作者：
Oddo, Salvatore