Reference - Detail
| RRC ID | 88137 |
|---|---|
| Author | Ricaurte-Perez C, Gill JP, Wall PK, Dubuisson O, DeLeo KR, Bohnert KA, Johnson AE. |
| Title | DAF-16/FOXO and HLH-30/TFEB comprise a cooperative regulatory axis controlling tubular lysosome induction in C. elegans. |
| Journal | Nat Commun |
| 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, including induction of vps-34 and related lipid-metabolism genes, that promote tubular-lysosome activity. Collectively, our work reveals a cellular process under control of DAF-16 and HLH-30 that elicits pro-health effects in aging. |
| Volume | 16(1) |
| Pages | 9878 |
| Published | 2025-11-10 |
| DOI | 10.1038/s41467-025-64832-x |
| PII | 10.1038/s41467-025-64832-x |
| PMID | 41213901 |
| PMC | PMC12603087 |
| MeSH | Aging / genetics Aging / metabolism Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / genetics Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / metabolism Basic Helix-Loop-Helix Proteins Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Forkhead Transcription Factors* / genetics Forkhead Transcription Factors* / metabolism Gene Expression Regulation Longevity / genetics Lysosomes* / genetics Lysosomes* / metabolism |
| Resource | |
| C.elegans | tm1978 |