溶酶体衰老图谱揭示与溶酶体贮积症共享的代谢物特征
溶酶体衰老图谱揭示与溶酶体贮积症共享的代谢物特征
作者： 小柯机器人 发布时间：2026/7/31 17:03:51
本期文章：《科学》：Volume 393 Issue 6810
美国Whitehead研究所Jonathan S. Weissman团队发现，溶酶体衰老图谱揭示了与溶酶体贮积症共享的代谢物特征。相关论文于2026年7月30日发表在《科学》杂志上。
课题组研究人员设计了一套快速分离溶酶体的工具，以构建溶酶体在衰老过程中代谢产物变化的多组织图谱。衰老的溶酶体在大脑、心脏、肌肉和白色脂肪组织中积累了甘油磷酸二酯和胱氨酸，这些代谢产物与幼年溶酶体储存障碍、巴滕病和胱氨酸病有直接联系。这些代谢物的水平随着年龄的增长而线性增加，在机体衰退之前。热量限制是一种延长寿命的干预措施，可以缓解心脏和肌肉的这些变化，但对大脑却没有作用。他们的发现将溶酶体贮积障碍与衰老相关功能障碍联系起来，并为溶酶体功能在衰老和年龄相关疾病中如何恶化的机制研究开辟了途径。
研究人员表示，溶酶体功能障碍是衰老的一个公认的特征。
附：英文原文
Title: Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders
Author: Anna M. Puszynska, Thao P. Nguyen, Andrew L. Cangelosi, Andrea Armani, Justin M. Roberts, Kristin A. Singh, James C. Cameron, Tenzin Tseyang, Grace Y. Liu, Steven Lai, Hans-Georg Sprenger, Jason Yang, William N. Colgan, Jibril F. Kedir, Kathrin M. Kajderowicz, Theodore K. Esantsi, Yuancheng Ryan Lu, Millenia Waite, Tenzin Kunchok, Caroline A. Lewis, Fabian Schulte, George W. Bell, David M. Sabatini, Jonathan S. Weissman
Issue&Volume: 2026-07-30
Abstract: Lysosomal dysfunction is a well-recognized feature of aging. Here, we used a suite of tools for rapid lysosomal isolation to construct a multitissue atlas of the metabolite changes lysosomes undergo during aging. Aged lysosomes in brain, heart, muscle, and white adipose tissue accumulated glycerophosphodiesters and cystine, metabolites that are causally linked to juvenile lysosomal storage disorders, Batten disease, and cystinosis. Levels of these metabolites increased linearly with age, preceding organismal decline. Caloric restriction, a lifespan-extending intervention, mitigated these changes in the heart and muscle but not the brain. Our findings link lysosomal storage disorders to aging-related dysfunction and open avenues for the mechanistic investigation of how lysosomal functions deteriorate during aging and in age-associated diseases.
DOI: ady0832
Source: https://www.science.org/doi/10.1126/science.ady0832