RT Journal Article SR Electronic T1 Neuronal TORC1 modulates longevity via AMPK and cell nonautonomous regulation of mitochondrial dynamics in C. elegans JF bioRxiv FD Cold Spring Harbor Laboratory SP 665190 DO 10.1101/665190 A1 Yue Zhang A1 Anne Lanjuin A1 Suvagata Roy Chowdhury A1 Meeta Mistry A1 Carlos G. Silva Garcia A1 Heather J. Weir A1 Chia-Lin Lee A1 Caroline C. Escoubas A1 Emina Tabakovic A1 William B. Mair YR 2019 UL http://biorxiv.org/content/early/2019/06/10/665190.abstract AB Target of rapamycin complex 1 (TORC1) and AMP-activated protein kinase (AMPK) antagonistically modulate metabolism and aging. However, how they coordinate to determine longevity and if they act via separable mechanisms is unclear. Here, we show that neuronal AMPK is essential for lifespan extension from TORC1 inhibition, and that TORC1 suppression increases lifespan cell non autonomously via distinct mechanisms from global AMPK activation. Lifespan extension by null mutations in genes encoding raga-1 (RagA) or rsks-1 (S6K) is fully suppressed by neuronal-specific rescues. Loss of RAGA-1 increases lifespan via maintaining mitochondrial fusion. Neuronal RAGA-1 abrogation of raga-1 mutant longevity requires UNC-64/syntaxin, and promotes mitochondrial fission cell nonautonomously. Finally, deleting the mitochondrial fission factor DRP-1 renders the animal refractory to the pro-aging effects of neuronal RAGA-1. Our results highlight a new role for neuronal TORC1 in cell nonautonomous regulation of longevity, and suggest TORC1 in the central nervous system might be targeted to promote healthy aging.