Aging is associated with a loss of metabolic homeostasis and plasticity, which is causally linked to multiple age-onset pathologies. The majority of the interventions—genetic, dietary, and pharmacological—that have been found to slow aging and protect against age-related disease in various organisms do so by targeting central metabolic pathways. However, targeting metabolic pathways chronically and ubiquitously makes it difficult to define the downstream effects responsible for lifespan extension and often results in negative effects on growth and health, limiting therapeutic potential. Insight into how metabolic signals are relayed between tissues, cells, and organelles opens up new avenues to target metabolic regulators locally rather than globally for healthy aging. In this review, we discuss the pro-longevity effects of targeting metabolic pathways in specific tissues and how these interventions communicate with distal cells to modulate aging. These studies may be crucial in designing interventions that promote longevity without negative health consequences.

衰老与代谢稳态和可塑性的丧失有关，这与多种年龄发病机理有因果关系。已发现大多数干预措施（遗传，饮食和药理学干预措施）可通过靶向中央代谢途径来延缓衰老并防止各种生物体中与年龄有关的疾病，从而可以达到这一目的。然而，长期和普遍地靶向代谢途径使得难以确定导致寿命延长的下游作用，并且常常导致对生长和健康的负面影响，限制了治疗潜力。对新陈代谢信号如何在组织，细胞和细胞器之间传递的深入了解，开辟了新途径，以局部而不是全局性地靶向代谢调节剂，从而实现健康衰老。在这篇评论中 我们讨论了在特定组织中靶向代谢途径的长寿效应，以及这些干预措施如何与远端细胞沟通以调节衰老。这些研究对于设计可延长寿命而不会对健康造成负面影响的干预措施至关重要。