Single-Cell Transcriptomics Uncovers Core Signature for Regulating Mitochondrial Homeostasis During Testicular Ageing.

Weijie Xu, Qiuru Huang, Yujuan Qi, Qingqing Hu, Cong Shen, Xia Chen, Jiaxin Li, Qiushi Xia, Ziyue Pan, Yi Zhang, Guoqing Han, Jingqi Huang, Yiheng Liu, Ziyu Cao, Ying Zheng, Bo Zheng, Zhifeng Gu, Jun Yu, Chi Sun

Department of Geriatrics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.Department of Geriatrics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China. · pubmed

Paper

Abstract

Testicular ageing is accompanied by a series of morphological changes, while the features of mitochondrial dysfunction remain largely unknown. Herein, we observed a range of age-related modifications in testicular morphology and spermatogenic cells, and conducted single-cell RNA sequencing on young and old testes in Drosophila. Pseudotime trajectory revealed significant changes in germline subpopulations during ageing. Our examination unveiled that genes showing bias in spermatids exhibited higher dN/dS than those in GSCs_Spermatogonia. Genes biased towards young GSCs_Spermatogonia displayed higher dN/dS than those in old GSCs_Spermatogonia. Interestingly, genes biased towards young spermatids demonstrated lower dN/dS in contrast to those in old spermatids, revealing the complexity of evolutionary adaptations during ageing. Furthermore, mitochondria associated events, including oxidative phosphorylation, TCA cycle and pyruvate metabolism, were significantly enriched in germline subpopulations. Specifically, mitochondrial function was significantly impaired during the process of testicular ageing, concurrently emphasising the role of several key nuclear genome-encoded mitochondrial regulatory genes, such as Hsp60B, fzo, Tim17b1 and mRpL12. Our data offer insights into testicular homeostasis regulated by mitochondrial function during the ageing process.

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Research summary

The paper investigates mitochondrial dysfunction in the context of testicular ageing, which is relevant to understanding the biological mechanisms of aging. It provides insights into the role of mitochondrial homeostasis in germline cells during the aging process, contributing to the broader field of longevity research. However, while the findings are solid and add to the understanding of age-related changes, they do not present groundbreaking discoveries or significant implications that would elevate the impact score beyond a solid contribution.

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