Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA.
Aging Cell. 2021 Jul;20(7):e13415. doi: 10.1111/acel.13415. Epub 2021 Jun 8.
Cellular senescence has emerged as a significant and potentially tractable mechanism of aging and multiple aging-related conditions. Biomarkers of senescent cell burden, including molecular signals in circulating immune cells and the abundance of circulating senescence-related proteins, have been associated with chronological age and clinical parameters of biological age in humans. The extent to which senescence biomarkers are affected by interventions that enhance health and function has not yet been examined. Here, we report that a 12-week structured exercise program drives significant improvements in several performance-based and self-reported measures of physical function in older adults. Impressively, the expression of key markers of the senescence program, including p16, p21, cGAS, and TNFα, were significantly lowered in CD3 T cells in response to the intervention, as were the circulating concentrations of multiple senescence-related proteins. Moreover, partial least squares discriminant analysis showed levels of senescence-related proteins at baseline were predictive of changes in physical function in response to the exercise intervention. Our study provides first-in-human evidence that biomarkers of senescent cell burden are significantly lowered by a structured exercise program and predictive of the adaptive response to exercise.
细胞衰老已成为衰老和多种与衰老相关疾病的一个重要且潜在的可干预机制。衰老细胞负担的生物标志物，包括循环免疫细胞中的分子信号和循环衰老相关蛋白的丰度，与人类的实际年龄和生物学年龄的临床参数相关。但增强健康和功能的干预措施对衰老生物标志物的影响程度尚未得到检验。在这里，我们报告称，为期 12 周的结构化运动计划可显著改善老年人多项基于表现和自我报告的身体功能测量。令人印象深刻的是，衰老程序的关键标志物的表达，包括 p16、p21、cGAS 和 TNFα，在 CD3 T 细胞中对干预的反应明显降低，同时多种与衰老相关的蛋白的循环浓度也降低了。此外，偏最小二乘判别分析显示，基线时的衰老相关蛋白水平可预测对运动干预的身体功能变化。我们的研究首次提供了人体证据，表明衰老细胞负担的生物标志物可通过结构化运动计划显著降低，并可预测对运动的适应性反应。
