Aging has been viewed both as a random process due to accumulation of molecular and cellular damage over time and as a programmed process linked to cellular pathway important for growth and maturation. These views converge on mitochondria as both the major producer of damaging reactive oxidant species (ROS) and as signaling organelles. A finite proton leak across the inner mitochondrial membrane leading to a slight uncoupling of oxidative phosphorylation and respiration is an intrinsic property of all mitochondria and according to the "uncoupling to survive" hypothesis it has evolved to protect against ROS production to minimize oxidative damage. This hypothesis is supported by evidence linking an increased endogenous, uncoupling protein (UCP1) mediated, as well as experimentally induced mitochondrial uncoupling to an increased lifespan in rodents. This is possibly due to the synergistic activation of molecular pathways linked to life extending effects of caloric restriction as well as a mitohormetic response. Mitohormesis is an adaptive stress response through mitonuclear signaling which increases stress resistance resulting in health promoting effects. Part of this response is the induction of fibroblast growth factor 21 (FGF21) and growth and differentiation factor 15 (GDF15), two stress-induced mitokines which elicit beneficial systemic metabolic effects via endocrine action.

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线粒体解偶联和长寿-线粒体的作用？

由于分子和细胞随时间的积累，衰老既被视为随机过程，又被视为与对生长和成熟重要的细胞途径相关的程序化过程。这些观点都集中于线粒体，它既是破坏性活性氧化剂（ROS）的主要生产者，又是信号传导的细胞器。跨线粒体内膜的有限质子泄漏导致氧化磷酸化和呼吸的轻微解偶联是所有线粒体的内在特性，根据“解偶联生存”的假设，它已发展为可防止ROS产生，从而将氧化损伤降至最低。该假设得到了与内源性，解偶联蛋白（UCP1）介导的内源性解偶联蛋白增加相关的证据的支持。以及通过实验诱导的线粒体解偶联延长了啮齿动物的寿命。这可能是由于与热量限制的寿命延长效应以及拟荷尔蒙反应有关的分子途径的协同活化所致。线粒体营养不良是通过微核信号传导的适应性应激反应，其增加了抗应激性，从而促进了健康。该反应的一部分是成纤维细胞生长因子21（FGF21）和生长与分化因子15（GDF15）的诱导，这两种应激诱导的丝裂霉素通过内分泌作用引起有益的全身代谢作用。线粒体营养不良是通过微核信号传导的适应性应激反应，其增加了抗应激性，从而促进了健康。该反应的一部分是成纤维细胞生长因子21（FGF21）和生长与分化因子15（GDF15）的诱导，这两种应激诱导的丝裂霉素通过内分泌作用引起有益的全身代谢作用。线粒体营养不良是通过微核信号传导的适应性应激反应，其增加了抗应激性，从而促进了健康。该反应的一部分是成纤维细胞生长因子21（FGF21）和生长与分化因子15（GDF15）的诱导，这两种应激诱导的丝裂霉素通过内分泌作用引起有益的全身代谢作用。