Exercise reduces circulating biomarkers of cellular senescence in humans.
Exercise reduces circulating biomarkers of cellular senescence in humans.
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DOI：
10.1111/acel.13415
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发表时间：
2021-07
期刊：
影响因子：
7.8
通讯作者：
LeBrasseur NK
中科院分区：
文献类型：
--
作者：
Englund DA;Sakamoto AE;Fritsche CM;Heeren AA;Zhang X;Kotajarvi BR;Lecy DR;Yousefzadeh MJ;Schafer MJ;White TA;Atkinson EJ;LeBrasseur NK
细胞衰老已成为衰老和多种衰老相关疾病的一种重要且潜在的可治疗机制。衰老细胞负荷的生物标志物，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富，与人类的时间年龄和临床生物年龄参数有关。促进健康和功能的干预措施对衰老生物标记物的影响程度尚未得到检查。在这里，我们报告说，一个为期12周的有组织的锻炼计划推动了老年人身体功能的几项基于表现和自我报告的指标的显著改善。令人印象深刻的是，在CD3+T细胞中，衰老程序的关键标志，包括p16，p21，cGAS和肿瘤坏死因子α的表达显著降低，多种衰老相关蛋白的循环浓度也显著降低。此外，偏最小二乘判别分析显示，基线时衰老相关蛋白的水平可以预测运动干预后身体功能的变化。我们的研究提供了第一个人类证据，表明有组织的运动计划显著降低了衰老细胞负担的生物标记物，并预测了运动的适应性反应。我们的研究提供了第一个人类证据，表明有组织的运动计划显著降低了衰老细胞负担的生物标记物，并预测了运动的适应性反应。
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. 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.
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影响因子：
7.8
作者：
Zhu Y;Tchkonia T;Pirtskhalava T;Gower AC;Ding H;Giorgadze N;Palmer AK;Ikeno Y;Hubbard GB;Lenburg M;O'Hara SP;LaRusso NF;Miller JD;Roos CM;Verzosa GC;LeBrasseur NK;Wren JD;Farr JN;Khosla S;Stout MB;McGowan SJ;Fuhrmann-Stroissnigg H;Gurkar AU;Zhao J;Colangelo D;Dorronsoro A;Ling YY;Barghouthy AS;Navarro DC;Sano T;Robbins PD;Niedernhofer LJ;Kirkland JL
通讯作者：
Kirkland JL
影响因子：
82.9
作者：
Farr JN;Xu M;Weivoda MM;Monroe DG;Fraser DG;Onken JL;Negley BA;Sfeir JG;Ogrodnik MB;Hachfeld CM;LeBrasseur NK;Drake MT;Pignolo RJ;Pirtskhalava T;Tchkonia T;Oursler MJ;Kirkland JL;Khosla S
通讯作者：
Khosla S
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
DOI：
10.1084/jem.20180139
发表时间：
2018-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li T;Chen ZJ
通讯作者：
Chen ZJ
影响因子：
8
作者：
Schafer, Marissa J.;Zhang, Xu;LeBrasseur, Nathan K.
通讯作者：
LeBrasseur, Nathan K.