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Main Menu - Block
- Overview
- Anatomy and Histology
- Cryo-Electron Microscopy
- Electron Microscopy
- Flow Cytometry
- Gene Targeting and Transgenics
- High Performance Computing
- Immortalized Cell Line Culture
- Integrative Imaging
- Invertebrate Shared Resource
- Janelia Experimental Technology
- Mass Spectrometry
- Media Prep
- Molecular Genomics
- Primary & iPS Cell Culture
- Project Pipeline Support
- Project Technical Resources
- Quantitative Genomics
- Scientific Computing
- Viral Tools
- Vivarium
Abstract
Epigenome is sensitive to metabolic inputs and crucial for aging. Lysosomes emerge as a signaling hub to sense metabolic cues and regulate longevity. We unveil that lysosomal metabolic pathways signal through the epigenome to regulate transgenerational longevity in Caenorhabditis elegans. We discovered that the induction of lysosomal lipid signaling and lysosomal AMP-activated protein kinase (AMPK), or the reduction of lysosomal mechanistic-target-of-rapamycin (mTOR) signaling, increases the expression of histone H3.3 variant and elevates H3K79 methylation, leading to lifespan extension across multiple generations. This transgenerational pro-longevity effect requires intestine-to-germline transportation of H3.3 and a germline-specific H3K79 methyltransferase, and can be recapitulated by overexpressing H3.3 or the H3K79 methyltransferase. This work uncovers a lysosome-epigenome signaling axis linking soma and germline to mediate the transgenerational inheritance of longevity.
bioRxiv preprint: https://www.biorxiv.org/content/early/2025/05/23/2025.05.21.652954
