Faculty of Sport and Health Sciences, Gerontology Research Center (GEREC), University of Jyväskylä, Jyväskylä, Finland.
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
J Gerontol A Biol Sci Med Sci. 2022 Aug 12;77(8):1569-1576. doi: 10.1093/gerona/glab270.
Epigenetic clocks are composite markers developed to predict chronological age or mortality risk from DNA methylation (DNAm) data. The present study investigated the associations between 4 epigenetic clocks (Horvath's and Hannum's DNAmAge and DNAm GrimAge and PhenoAge) and physical functioning during a 3-year follow-up.
We studied 63- to 76-year-old women (N = 413) from the Finnish Twin Study on Aging. DNAm was measured from blood samples at baseline. Age acceleration (AgeAccel), that is, discrepancy between chronological age and DNAm age, was determined as residuals from linear model. Physical functioning was assessed under standardized laboratory conditions at baseline and at follow-up. A cross-sectional analysis was performed with path models, and a longitudinal analysis was conducted with repeated measures linear models. A nonrandom missing data analysis was performed.
In comparison to the other clocks, GrimAgeAccel was more strongly associated with physical functioning. At baseline, GrimAgeAccel was associated with lower performance in the Timed Up and Go (TUG) test and the 6-minute walk test. At follow-up, significant associations were observed between GrimAgeAccel and lowered performance in the TUG, 6-minute and 10-m walk tests, and knee extension and ankle plantar flexion strength tests.
The DNAm GrimAge, a novel estimate of biological aging, associated with decline in physical functioning over the 3-year follow-up in older women. However, associations between chronological age and physical function phenotypes followed similar pattern. Current epigenetic clocks do not provide strong benefits in predicting the decline of physical functioning at least during a rather short follow-up period and restricted age range.
表观遗传钟是一种综合标志物，用于根据 DNA 甲基化 (DNAm) 数据预测年龄或死亡率。本研究调查了 4 种表观遗传钟（Horvath 和 Hannum 的 DNAmAge 和 DNAm GrimAge 以及 PhenoAge）与 3 年随访期间身体机能之间的关联。
我们研究了来自芬兰衰老双胞胎研究的 63 至 76 岁女性（N=413）。在基线时从血液样本中测量 DNAm。年龄加速（AgeAccel），即实际年龄与 DNAm 年龄之间的差异，是通过线性模型的残差确定的。在基线和随访时在标准化实验室条件下评估身体机能。使用路径模型进行横断面分析，使用重复测量线性模型进行纵向分析。进行了非随机缺失数据分析。
与其他时钟相比，GrimAgeAccel 与身体机能的相关性更强。在基线时，GrimAgeAccel 与计时起立行走测试（TUG）和 6 分钟步行测试的表现较差相关。在随访时，GrimAgeAccel 与 TUG、6 分钟和 10 米步行测试以及膝关节伸展和踝关节跖屈力量测试的表现降低显著相关。
DNAm GrimAge 是一种新的生物衰老估计值，与老年女性 3 年随访期间身体机能下降有关。然而，实际年龄和身体机能表型之间的关联遵循相似的模式。目前的表观遗传钟在预测身体机能下降方面没有提供明显的优势，至少在相对较短的随访期和受限的年龄范围内是这样。
