Mitochondrial network remodeling between fused and fragmented states facilitates mitophagy, interaction with other organelles, and metabolic flexibility. Aging is associated with a loss of mitochondrial network homeostasis, but cellular processes causally linking these changes to organismal senescence remain unclear. Here, we show that AMP-activated protein kinase (AMPK) and dietary restriction (DR) promote longevity inC. elegansvia maintaining mitochondrial network homeostasis and functional coordination with peroxisomes to increase fatty acid oxidation (FAO). Inhibiting fusion or fission specifically blocks AMPK- and DR-mediated longevity. Strikingly, however, preserving mitochondrial network homeostasis during aging by co-inhibition of fusion and fission is sufficient itself to increase lifespan, while dynamic network remodeling is required for intermittent fasting-mediated longevity. Finally, we show that increasing lifespan via maintaining mitochondrial network homeostasis requires FAO and peroxisomal function. Together, these data demonstrate that mechanisms that promote mitochondrial homeostasis and plasticity can be targeted to promote healthy aging.

中文翻译：

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饮食限制和AMPK通过线粒体网络和过氧化物酶体重塑延长寿命

融合状态和碎片状态之间的线粒体网络重塑有助于线粒体，与其他细胞器的相互作用以及代谢灵活性。衰老与线粒体网络动态平衡的丧失有关，但是将这些变化与机体衰老相关的细胞过程尚不清楚。在这里，我们显示AMP激活的蛋白激酶（AMPK）和饮食限制（DR）促进inC的寿命。线虫保持线粒体网络稳态，并与过氧化物酶体保持功能协调，以增加脂肪酸氧化（FAO）。抑制融合或裂变可特异性阻断AMPK和DR介导的寿命。然而，令人惊讶的是，通过共同抑制融合和裂变来保持衰老过程中的线粒体网络稳态足以增加其寿命，而动态网络重塑对于间歇性禁食介导的寿命是必需的。最后，我们表明，通过维持线粒体网络动态平衡来延长寿命需要粮农组织和过氧化物酶体功能。总之，这些数据表明，促进线粒体动态平衡和可塑性的机制可以促进健康的衰老。