Mechanisms of Aging-Related Impairment of Brown Adipocyte Development and Function
Mechanisms of Aging-Related Impairment of Brown Adipocyte Development and Function
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DOI：
10.1159/000366557
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发表时间：
2015-01-01
期刊：
影响因子：
3.5
通讯作者：
Schulz, Tim J.
中科院分区：
文献类型：
--
作者：
Graja, Antonia;Schulz, Tim J.
衰老是肥胖的主要危险因素之一，肥胖是由于能量消耗增加与消耗减少之间的不平衡而产生的一种病理现象。棕色脂肪细胞负责产热，因此可以通过增加能量消耗来对抗肥胖。目前已经确定，人类一生都具有产热能力的棕色脂肪细胞，最近的研究表明，棕色脂肪积极参与成人的代谢控制和体重调节。衰老伴随着经典棕色脂肪细胞以及白色脂肪组织中发现的棕色样脂肪细胞的丧失，这表明随着年龄的增长，它们能量消耗能力的丧失可能导致肥胖倾向的表型。我们在此讨论棕色脂肪细胞再生能力与年龄相关的丧失是干细胞/祖细胞功能失调的结果。导致棕色脂肪干细胞/祖细胞功能与年龄相关的下降的可能分子机制包括细胞自主和外部效应。线粒体生物发生和功能的普遍丧失一再与年龄相关的代谢过程的扰动有关。我们还讨论了交感神经系统神经元控制的改变可能导致衰老棕色脂肪细胞再生和产热功能受损的可能性。最后，年龄相关的内分泌信号变化被认为会加剧棕色脂肪组织的损失。综上所述，年龄引起的棕色脂肪干细胞/祖细胞功能损伤可能导致棕色脂肪细胞再生丧失，从而促进肥胖和其他代谢紊乱的发生。(C) 2014 S. Karger AG，巴塞尔
Aging is one of the primary risk factors for the development of obesity, a pathology that develops due to an imbalance of increased energy consumption over reduced expenditure. Brown adipocytes are responsible for thermogenesis and could therefore counter obesity by increasing energy expenditure. It is by now well established that humans possess thermogenesis-competent brown adipocytes throughout life, and recent findings indicate that brown fat is actively involved in metabolic control and body weight regulation in adults. Aging is accompanied by a loss of classical brown adipocytes as well as the brown-like adipocytes found in white adipose tissue, suggesting that loss of their energy-expending capacity might contribute to an obesity-prone phenotype with increased age. We here discuss the hypothesis that the age-related loss of brown adipocyte regenerative capacity is a result of dysfunctional stem/progenitor cells. The possible molecular mechanisms that lead to an age-related decline in brown adipogenic stem/progenitor cell function include cell-autonomous and external effects. General loss of mitochondrial biogenesis and function has repeatedly been linked to age-related perturbation of metabolic processes. We also discuss the possibility that alterations in neuronal control by the sympathetic nervous system may contribute to impaired regeneration and thermogenesis in aged brown adipocytes. Finally, age-related changes of endocrine signals have been proposed to exacerbate the loss of brown adipose tissue. In conclusion, age-induced impairment of brown adipogenic stem/progenitor cell function could contribute to the loss of brown adipocyte regeneration, thereby promoting the development of obesity and other metabolic disorders with age. (C) 2014 S. Karger AG, Basel