DAF-16/FOXO and HLH-30/TFEB comprise a cooperative regulatory axis controlling tubular lysosome induction in C. elegans.

ABSTRACT: Transcription factors DAF-16/FOXO and HLH-30/TFEB have been linked to aging regulation, but how they synergize to promote longevity is not fully understood. Here, we reveal a functional interaction between these two transcription factors that supports healthier aging in Caenorhabditis elegans. Namely, DAF-16 and HLH-30 cooperate to trigger robust lysosomal tubulation under various contexts, which contributes to systemic health benefits in late age. Remarkably, lysosome tubulation can be artificially induced via overexpression of a small lysosomal gene, dSVIP, in the absence of one transcription factor, but not both. Mechanistically, intestinal overexpression of dSVIP leads to nuclear accumulation of DAF-16 and HLH-30 in gut and non-gut tissues and triggers global gene expression changes, i

SUBMITTER: Ricaurte-Perez C 

PROVIDER: S-EPMC12603087 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature