热量限制调节小鼠全基因组体细胞突变
热量限制调节小鼠全基因组体细胞突变
作者： 小柯机器人 发布时间：2026/9/11 19:53:11
本期文章：《细胞》：Online/在线发表
美国纽约大学格罗斯曼医学院Gilad D. Evrony研究组的一项最新研究揭示了热量限制调节小鼠全基因组体细胞突变。相关论文于近日发表在《细胞》杂志上。
体细胞突变在生命过程中于每个细胞中累积，这一过程构成衰老的标志之一——基因组不稳定性。热量限制已被证明可延长多种物种的寿命。研究人员利用高保真双链DNA测序对整体肝脏、整体肾脏、肝细胞和小脑神经元进行分析，发现小鼠热量限制降低了多种组织和细胞类型的全基因组体细胞突变负荷。热量限制减少了替换和插入/缺失负荷，其影响程度因样本类型而异。热量限制还降低了神秘的单碱基替换（SBS）突变过程SBS5的活性，该过程产生了哺乳动物中的大多数突变。令人惊讶的是，热量限制带来的突变负荷降低在转录不活跃区域最为显著。这项工作阐明了饮食、衰老与基因组完整性之间的联系，并将基因组完整性确立为衰老的一个可修改轴。
附：英文原文
Title: Caloric restriction modulates genome-wide somatic mutation in mice
Author: Marta Grońska-Pski, Victoria Acosta-Rodríguez, Amoolya Srinivasa, Amanda Garrido, Shany Picciotto, Carla B. Green, Joseph S. Takahashi, Jonathan E. Shoag, Gilad D. Evrony
Issue&Volume:
Abstract: Somatic mutations accumulate throughout life in every cell, and this process constitutes one of the hallmarks of aging—genomic instability. Caloric restriction (CR) has been shown to extend lifespan across diverse species. Using high-fidelity duplex DNA sequencing of bulk liver, bulk kidney, hepatocytes, and cerebellar neurons, we found that CR in mice reduces genome-wide somatic mutation burdens across multiple tissues and cell types. CR reduced both substitution and insertion/deletion burdens, with the magnitude of these effects varying across sample types. CR also decreased the activity of the enigmatic single-base substitution (SBS) mutational process SBS5 that gives rise to most mutations in mammals. Surprisingly, the mutation burden reduction from CR was greatest in transcriptionally inactive regions. This work illuminates links between diet, aging, and genomic integrity and establishes genomic integrity as a modifiable axis of aging.
DOI: 10.1016/j.cell.2026.08.013
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00940-2