Neuronal HLH-30/TFEB modulates thermoresistance and longevity in C. elegans

The conserved autophagy(definition) transcription factor HLH-30/TFEB is a well-established modulator of lifespan in several mechanistically-distinct longevity paradigms in C. elegans. While various tissues contribute differentially to organismal lifespan, neurons are particularly interesting as they can mediate adaptive response to environmental and proteostatic stresses. Using carefully-designed neuronal-specific reconstitution of HLH-30 in loss of function hlh-30 mutants, we found a role for neuronal HLH-30 in modulating longevity and heat stress response via neurotransmission-mediated peripheral mitochondrial fragmentation. Altogether, we demonstrated new links between neuronal HLH-30 function, thermoresistance and organismal aging.