该研究组发现，溶酶体代谢途径通过表观基因组信号调节秀丽隐杆线虫的跨代寿命。激活溶酶体脂质信号和溶酶体单磷酸腺苷活化蛋白激酶（AMPK）或减少溶酶体雷帕霉素机制靶蛋白（mTOR）信号可增加组蛋白H3.3变体的表达并增加其在K79上的甲基化，从而延长多代人的寿命。这种跨代延长寿命的作用需要组蛋白H3.3和种系特异性H3K79甲基转移酶从肠道到种系的转运，并通过过表达H3.3或H3K79甲基转移酶来重现。因此，来自溶酶体的信号影响表观基因组，连接体细胞和生殖系，介导长寿的跨代遗传。
据悉，表观基因组对代谢输入敏感，对衰老至关重要。溶酶体作为信号中枢，感知代谢信号并调节寿命。
附：英文原文
Title: Lysosomes signal through the epigenome to regulate longevity across generations
Author: Qinghao Zhang, Weiwei Dang, Meng C. Wang
Issue&Volume: 2025-09-25
Abstract: The epigenome is sensitive to metabolic inputs and is crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We found that lysosomal metabolic pathways signal through the epigenome to regulate transgenerational longevity in Caenorhabditis elegans. Activation of lysosomal lipid signaling and lysosomal adenosine monophosphate–activated protein kinase (AMPK) or reduction of lysosomal mechanistic target of rapamycin (mTOR) signaling increased the expression of a histone H3.3 variant and increased its methylation on K79, leading to life-span extension across multiple generations. This transgenerational prolongevity effect required intestine-to-germline transportation of histone H3.3 and a germline-specific H3K79 methyltransferase and was recapitulated by overexpressing H3.3 or the H3K79 methyltransferase. Thus, signals from a lysosome affect the epigenome and link the soma and germ line to mediate transgenerational inheritance of longevity.
DOI: adn8754
Source: https://www.science.org/doi/10.1126/science.adn8754