Juan Luis Sánchez-Sánchez, Bruno Vellas, Sophie Guyonnet, Paul Bensadoun, Jean-Marc Lemaitre, Matias Fuentealba Valenzuela, Fabien Pillard, Yves Rolland, David Furman, Philipe de Souto Barreto
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Here, we explored the associations of biological age acceleration (BAA) assessed by Horvath's, Hannum's, PhenoAge, and GrimAge epigenetic clocks, as well as the iAge inflammation-based clock, with functional capacities across adulthood and tested if chronological age and sex moderate these associations.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Cross-sectional analysis was conducted with baseline (2019–2021) data from 1014 participants (age range 20–104 years old, 62.82% female) drawn from the Inspire Translational Human cohort, a community-based program in South-West France. Physical capacity endpoints included the five-time sit-to-stand test (5-STS), the Short Physical Performance Battery (SPPB), the 30-s chair stand test (30-s CST), maximum oxygen uptake (VO2max) and isokinetic muscle strength (IMS). Multivariate linear regression was used to explore the associations of BAA (with and without interacting with chronological age or sex) with functional capacity endpoints.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A total of 1014 individuals with available data on BAA and functional capacities were included (median age 64, IQR = 49–78, 62.82% female). GrimAge was the clock that more strongly correlated with functional capacities. Higher GrimAge BAA was associated with worse 5-STS (β = 0.25, 95% CI = 0.07, 0.43; <i>p</i> = 0.002), SPPB (β = −0.10, 95% CI = −0.18, −0.02; <i>p</i> = 0.019) and VO2max (β = −1.17, 95% CI = −1.81, −0.52; <i>p</i> < 0.001) across the whole adulthood. When the moderation effect of age was explored, BAA acceleration assessed by GrimAge was associated with worse 30-s CST in early adulthood. Increased iAge BAA was associated with poor SPPB and 5-STS at older age, whereas Horvath's BAA correlated with a decline in 30-s CST.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Among four DNA methylation epigenetic clocks and one inflammatory clock, our study shows that GrimAge is the biological ageing clock that best associates with different measures of functional capacity, from young to older adulthood.</p>\n </section>\n </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1000,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70046","citationCount":"0","resultStr":"{\"title\":\"Biological Ageing Acceleration and Functional Capacities Across the Lifespan in the INSPIRE-T Cohort\",\"authors\":\"Juan Luis Sánchez-Sánchez, Bruno Vellas, Sophie Guyonnet, Paul Bensadoun, Jean-Marc Lemaitre, Matias Fuentealba Valenzuela, Fabien Pillard, Yves Rolland, David Furman, Philipe de Souto Barreto\",\"doi\":\"10.1002/jcsm.70046\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Biological clocks are promising tools for the evaluation of biological age deviations (i.e., positive/negative acceleration). 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引用次数: 0
摘要
生物时钟是评估生物年龄偏差（即正/负加速度）的有前途的工具。在这里，我们探讨了由Horvath、Hannum、PhenoAge和GrimAge表观遗传时钟以及基于炎症的图像时钟评估的生物年龄加速（BAA）与成年期功能能力的关联，并测试了实际年龄和性别是否调节了这些关联。方法对来自法国西南部社区项目Inspire Translational Human队列的1014名参与者（年龄在20-104岁之间，62.82%为女性）的基线（2019-2021年）数据进行横断面分析。体能终点包括5次坐立测试（5-STS）、短物理性能电池（SPPB）、30秒椅子站立测试（30-s CST）、最大摄氧量（VO2max）和等速肌力（IMS）。采用多元线性回归探讨BAA（与实足年龄或性别有或无相互作用）与功能能力终点的关系。结果共纳入1014例BAA和功能能力资料，中位年龄64岁，IQR = 49 ~ 78，女性62.82%。GrimAge是与功能能力更紧密相关的时钟。GrimAge BAA越高，5-STS越差(β = 0.25, 95% CI = 0.07, 0.43；p = 0.002), SPPB(β=−0.10,95% CI =−0.18−0.02;p = 0.019)和摄氧量(β=−1.17,95% CI =−1.81−0.52;P < 0.001)。当年龄的调节作用被探索时，GrimAge评估的BAA加速与成年早期30-s CST较差相关。年龄BAA升高与老年SPPB和5-STS不良相关，而Horvath BAA与30-s CST下降相关。在四个DNA甲基化表观遗传时钟和一个炎症时钟中，我们的研究表明，GrimAge是与从年轻到老年的不同功能测量最相关的生物衰老时钟。
Biological Ageing Acceleration and Functional Capacities Across the Lifespan in the INSPIRE-T Cohort
Background
Biological clocks are promising tools for the evaluation of biological age deviations (i.e., positive/negative acceleration). Here, we explored the associations of biological age acceleration (BAA) assessed by Horvath's, Hannum's, PhenoAge, and GrimAge epigenetic clocks, as well as the iAge inflammation-based clock, with functional capacities across adulthood and tested if chronological age and sex moderate these associations.
Methods
Cross-sectional analysis was conducted with baseline (2019–2021) data from 1014 participants (age range 20–104 years old, 62.82% female) drawn from the Inspire Translational Human cohort, a community-based program in South-West France. Physical capacity endpoints included the five-time sit-to-stand test (5-STS), the Short Physical Performance Battery (SPPB), the 30-s chair stand test (30-s CST), maximum oxygen uptake (VO2max) and isokinetic muscle strength (IMS). Multivariate linear regression was used to explore the associations of BAA (with and without interacting with chronological age or sex) with functional capacity endpoints.
Results
A total of 1014 individuals with available data on BAA and functional capacities were included (median age 64, IQR = 49–78, 62.82% female). GrimAge was the clock that more strongly correlated with functional capacities. Higher GrimAge BAA was associated with worse 5-STS (β = 0.25, 95% CI = 0.07, 0.43; p = 0.002), SPPB (β = −0.10, 95% CI = −0.18, −0.02; p = 0.019) and VO2max (β = −1.17, 95% CI = −1.81, −0.52; p < 0.001) across the whole adulthood. When the moderation effect of age was explored, BAA acceleration assessed by GrimAge was associated with worse 30-s CST in early adulthood. Increased iAge BAA was associated with poor SPPB and 5-STS at older age, whereas Horvath's BAA correlated with a decline in 30-s CST.
Conclusions
Among four DNA methylation epigenetic clocks and one inflammatory clock, our study shows that GrimAge is the biological ageing clock that best associates with different measures of functional capacity, from young to older adulthood.
期刊介绍：
The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.
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