Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
J Exp Biol. 2014 Jan 1;217(Pt 1):109-18. doi: 10.1242/jeb.089920.
Aging is characterized by a widespread loss of homeostasis in biological systems. An important part of this decline is caused by age-related deregulation of regulatory processes that coordinate cellular responses to changing environmental conditions, maintaining cell and tissue function. Studies in genetically accessible model organisms have made significant progress in elucidating the function of such regulatory processes and the consequences of their deregulation for tissue function and longevity. Here, we review such studies, focusing on the characterization of processes that maintain metabolic and proliferative homeostasis in the fruitfly Drosophila melanogaster. The primary regulatory axis addressed in these studies is the interaction between signaling pathways that govern the response to oxidative stress, and signaling pathways that regulate cellular metabolism and growth. The interaction between these pathways has important consequences for animal physiology, and its deregulation in the aging organism is a major cause for increased mortality. Importantly, protocols to tune such interactions genetically to improve homeostasis and extend lifespan have been established by work in flies. This includes modulation of signaling pathway activity in specific tissues, including adipose tissue and insulin-producing tissues, as well as in specific cell types, such as stem cells of the fly intestine.
衰老是生物系统中普遍失去内稳态的特征。这种衰退的一个重要部分是由与年龄相关的调节过程失调引起的，这些过程协调细胞对环境变化的反应，维持细胞和组织的功能。在遗传上可访问的模式生物中的研究在阐明这些调节过程的功能以及它们对组织功能和寿命的失调的后果方面取得了重大进展。在这里，我们回顾了这些研究，重点介绍了维持果蝇黑腹果蝇代谢和增殖内稳态的过程的特征。这些研究中主要的调节轴是调节对氧化应激反应的信号通路与调节细胞代谢和生长的信号通路之间的相互作用。这些途径之间的相互作用对动物生理学有重要的影响，其在衰老生物体内的失调是导致死亡率增加的主要原因。重要的是，通过在果蝇中的工作，已经建立了通过遗传方式调整这种相互作用以改善内稳态和延长寿命的方案。这包括调节特定组织（包括脂肪组织和产生胰岛素的组织）以及特定细胞类型（如果蝇肠道的干细胞）中的信号通路活性。
