Mitochondrial double-stranded RNA drives aging-associated cognitive decline.

Lixiao Zhang, Xiang Li, Hongdi Luo, Yujia Huo, Guangkeng Zhou, Pengcheng Wang, Sipeng Wu, Xinyong Lin, Kai Dai, Jiahao Shi, Zebao Wang, Jiaxin Xu, Renjian Li, Siyi Chen, Zhe Sun, Chunlin Zhao, Zizhuo Zhou, Zhenhong Wang, Chensi Liang, Jun Zhu, Xingjun Chen, Jintao Luo, Yong Yu, Zhirong Zhang, Geng Wang

State Key Laboratory for Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.State Key Laboratory for Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China. · pubmed

Paper

Abstract

Aging is the primary cause of cognitive decline. Despite extensive study, the molecular mechanisms driving aging-associated cognitive decline remain unclear. Here, we describe a proteostasis-independent function of SEC61A1 and its involvement in aging-associated cognitive decline. SEC61A1 regulates ER-mitochondria contact sites, affecting mitochondrial DNA and RNA synthesis and subsequently leading to changes in innate immune signaling mediated by mitochondrial double-stranded RNA (mt-dsRNA). This pathway is activated in aged wild-type mice, Alzheimer's disease patients, and 5×FAD mice. Tissue-specific overexpression of Sec61a1 in the mouse cortex (Sec61a1

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Research summary

The paper claims that SEC61A1 regulates mitochondrial double-stranded RNA synthesis, which contributes to aging-associated cognitive decline. This research addresses a potential molecular mechanism underlying cognitive decline in aging, which is relevant to understanding the root causes of aging and age-related diseases.

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