Preserved mitochondrial ribosomal protein gene expression marks a youthful transcriptional state in Chinese nonagenarians and centenarians.

Fu-Hui Xiao, Hao-Tian Wang, Long Zhao, Gong-Hua Li, Si-Yu Ma, Li-Qin Yang, Hua Wang, Yun-Xia Zhang, Ji Li, Qing-Peng Kong

State Key Laboratory of Genetic Evolution and Animal Models, Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Department of Cardiology, The Affiliated Lihuili Hospital of Ningbo University, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: [email protected] Key Laboratory of Genetic Evolution and Animal Models, Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Department of Cardiology, The Affiliated Lihuili Hospital of Ningbo University, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: [email protected]. · pubmed

Paper

Abstract

A youthful molecular profile reflects attenuated aging and preserved health in advanced age. Long-lived individuals (LLIs) show youthful patterns in DNA methylation and gut microbiota, yet their transcriptional trajectories remain undercharacterized. We analyze transcriptomes from 811 LLIs and 940 younger controls (YCs) to map transcriptional aging trajectories. Clocks trained on YCs reveal that LLIs possess markedly younger transcriptional ages than expected. We identify gene clusters deviating from YC-derived aging trajectories in LLIs, notably eight mitochondrial ribosomal protein genes (mRPGs) resisting typical age-related expression decline. An elevated 8-mRPG expression score correlates with lower aging levels inferred from established aging- and senescence-related gene gets. Samples with higher 8-mRPG scores exhibit increased expression of mitochondrial-function-related genes, including those in aerobic respiration and respiratory electron transport. Together, these findings indicate that the sustained expression of specific mRPGs in LLIs is a signature of attenuated transcriptomic aging that may reflect preserved mitochondrial function.

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Research summary

The paper claims that preserved expression of specific mitochondrial ribosomal protein genes in long-lived individuals indicates a youthful transcriptional state. This research is relevant as it explores the molecular underpinnings of aging and longevity, focusing on transcriptional aging trajectories and their implications for mitochondrial function in long-lived individuals.

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