category
bioRxiv
date
Feb 22, 2026
slug
status
Published
summary
首次直接比较TCR多样性与表观遗传时钟在健康衰老评估中的差异,发现TCR多样性可区分健康老人与虚弱个体,而表观遗传时钟受CMV感染状态显著影响;揭示CMV感染导致免疫系统衰老的机制,即健康老人依赖CD4+ T细胞控制CMV,而虚弱老人则由CD8+ T细胞承担,伴随TCR多样性降低和CMV相关TCR比例升高。
tags
测序技术
type
Post

📄 原文题目

The T cell receptor repertoire captures healthy aging and CMV independently from epigenetic clocks

🔗 原文链接

💡 AI 核心解读

首次直接比较TCR多样性与表观遗传时钟在健康衰老评估中的差异,发现TCR多样性可区分健康老人与虚弱个体,而表观遗传时钟受CMV感染状态显著影响;揭示CMV感染导致免疫系统衰老的机制,即健康老人依赖CD4+ T细胞控制CMV,而虚弱老人则由CD8+ T细胞承担,伴随TCR多样性降低和CMV相关TCR比例升高。

📝 英文原版摘要

Human aging is the process through which numerous biological changes occur during life, affecting various processes. In some elderly individuals, this functional decline becomes more pronounced, leading to frailty, a condition characterised by reduced physiological reserves and increased vulnerability to stress. With the global rise of life expectancy, identification of biomarkers for healthspan and frailty are becoming more important. In this study, we directly compare two molecular readouts, namely the T cell receptor (TCR) repertoire and epigenetic clocks, on their ability to discern healthy aging. On blood samples from sixteen individuals, across age-matched healthy elderly and frail individuals, both TCR sequencing and epigenetic profiling were performed. A significantly higher TCR repertoire diversity in the CD4+ T cells differentiated the healthy elderly individuals from the frailty ones. Epigenetic clock signatures of biological relative to chronological ageing rate, did not show a clear difference between both groups. However, when taking into account the CMV-serostatus, a significant increase in epigenetic aging could be observed in the CMV-seropositive individuals. Our results support a clear hypothesis on the role of CMV infection in the healthy aging of the immune system. In healthy elderly, CMV is typically controlled by CD4+ T cells, however, in the frail elderly, the burden of managing the infection shifts to the CD8+ T cells. This change is marked by two key changes: a decrease in TCR diversity for seropositive individuals compared to seronegative individuals, as well as an increase in the fraction of CMV-associated TCRs within the CD8+ T cells. These findings contribute to our understanding of aging and provide insight into how CMV-infection may affect
healthy aging and frailty. They also underline the crucial role of the immune system in healthy aging and the value of further investigating ageing-related health/disease patterns in the TCR repertoire to determine healthspan/lifespan.
增强的无细胞基因表达用于微滴中单拷贝DNA模板的稳健信号读取基于TRIzol的灭活协议与细菌选择性代理物故障场景测试的验证
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