Maglioni Silvia, Mello Danielle F, Schiavi Alfonso, Meyer Joel N, Ventura Natascia
IUF-Leibniz Research Institute for Environmental Medicine, 40225 Duesseldorf, Germany.
Nicholas School of the Environment and Integrated Toxicology and Environmental Health Program, Duke University, Durham, NC 27708, USA.
Aging (Albany NY). 2019 Aug 27;11(16):6535-6554. doi: 10.18632/aging.102208.
Mild suppression of mitochondrial activity has beneficial effects across species. The nematode is a versatile, genetically tractable model organism widely employed for aging studies, which has led to the identification of many of the known evolutionarily conserved mechanisms regulating lifespan. In the pro-longevity effect of reducing mitochondrial function, for example by RNA interference, is only achieved if mitochondrial stress is applied during larval development. Surprisingly, a careful analysis of changes in mitochondrial functions resulting from such treatments during the developmental windows in which pro-longevity signals are programmed has never been carried out. Thus, although the powerful genetics have led to the identification of different molecular mechanisms causally involved in mitochondrial stress control of longevity, specific functional mitochondrial biomarkers indicative or predictive of lifespan remain to be identified. To fill this gap, we systematically characterized multiple mitochondrial functional parameters at an early developmental stage in animals that are long-lived due to mild knockdown of twelve different mitochondrial proteins and correlated these parameters with animals' lifespan. We found that basal oxygen consumption rate and ATP-linked respiration positively correlate with lifespan extension and propose the testable hypothesis that the Bioenergetic Health Index can be used as a proxy to predict health-span outcomes.
线粒体活性的轻度抑制在不同物种中都具有有益作用。线虫是一种用途广泛、基因易于操作的模式生物，被广泛用于衰老研究，这使得许多已知的调节寿命的进化保守机制得以确定。例如，只有在幼虫发育期间施加线粒体应激，通过RNA干扰等方式降低线粒体功能的促长寿效应才能实现。令人惊讶的是，从未有人对在长寿信号被编程的发育窗口期间此类处理导致的线粒体功能变化进行过仔细分析。因此，尽管强大的遗传学已经确定了不同的分子机制因果性地参与线粒体应激对寿命的控制，但指示或预测寿命的特定功能性线粒体生物标志物仍有待确定。为了填补这一空白，我们系统地表征了由于十二种不同线粒体蛋白的轻度敲低而长寿的动物在早期发育阶段的多个线粒体功能参数，并将这些参数与动物的寿命相关联。我们发现基础氧消耗率和ATP相关呼吸与寿命延长呈正相关，并提出了一个可检验的假设，即生物能量健康指数可以用作预测健康寿命结果的指标。
