Cellular Senescence in Obesity and Associated Complications: a New Therapeutic Target.
Cellular Senescence in Obesity and Associated Complications: a New Therapeutic Target.
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DOI：
10.1007/s11892-022-01493-w
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发表时间：
2022-11
影响因子：
4.2
通讯作者：
Niedernhofer, Laura J.
中科院分区：
文献类型：
--
作者：
Narasimhan, Akilavalli;Flores, Rafael R.;Camell, Christina D.;Bernlohr, David A.;Robbins, Paul D.;Niedernhofer, Laura J.
近年来，肥胖症在全球范围内增加，并成为一项重大的全球健康挑战。本文综述了肥胖相关的细胞衰老在各种器官中的作用，这些衰老细胞（SnCs）在驱动与肥胖相关的并发症。此外，靶向SnCs的能力与药物称为senotherapeutics作为这些并发症的治疗进行了讨论。几项研究表明，肥胖与器官（如脂肪组织、肝脏和胰腺-β-细胞）中的SnC负荷呈正相关。这些SnCs产生几种分泌因子，其以旁分泌方式影响其他细胞和组织，导致器官功能障碍。SnCs在脂肪细胞中的积累影响其脂质储存并损害脂肪形成。SnCs的炎性衰老相关分泌表型（SASP）下调组织中的抗氧化能力和线粒体功能。衰老的肝细胞不能氧化脂肪酸，这导致脂质沉积，并且β细胞的衰老降低功能。SnCs的这些和其他副作用导致胰岛素抵抗和2型糖尿病。SnC负担的减少在遗传上或遗传上改善了与肥胖相关的并发症。随着年龄和疾病的积累，SnC加速衰老。肥胖是SnC积累的关键驱动因素，与肥胖相关的并发症可以通过减少SnC负担来控制。因此，塞那普利药物有可能成为一种有效的治疗选择。
Obesity has increased worldwide recently and represents a major global health challenge. This review focuses on the obesity-associated cellular senescence in various organs and the role of these senescent cells (SnCs) in driving complications associated with obesity. Also, the ability to target SnCs pharmacologically with drugs termed senotherapeutics as a therapy for these complications is discussed. Several studies have shown a positive correlation between obesity and SnC burden in organs such as adipose tissue, liver, and pancreatic-β-cells. These SnCs produce several secretory factors which affect other cells and tissues in a paracrine manner resulting in organ dysfunction. The accumulation of SnCs in adipocytes affects their lipid storage and impairs adipogenesis. The inflammatory senescence-associated secretory phenotype (SASP) of SnCs downregulates the antioxidant capacity and mitochondrial function in tissues. Senescent hepatocytes cannot oxidize fatty acids, which leads to lipid deposition and senescence in β-cells decrease function. These and other adverse effects of SnCs contribute to insulin resistance and type-2 diabetes. The reduction in the SnC burden genetically or pharmacologically improves the complications associated with obesity. The accumulation of SnCs with age and disease accelerates aging. Obesity is a key driver of SnC accumulation, and the complications associated with obesity can be controlled by reducing the SnC burden. Thus, senotherapeutic drugs have the potential to be an effective therapeutic option.
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影响因子：
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DOI：
10.1083/jcb.201608026
发表时间：
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期刊：
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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