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. 2021 Jul;20(7):e13415.
doi: 10.1111/acel.13415. Epub 2021 Jun 8.

Exercise reduces circulating biomarkers of cellular senescence in humans

Davis A Englund  1   2 , Ayumi E Sakamoto  1   2 , Chad M Fritsche  3 , Amanda A Heeren  1   2 , Xu Zhang  1 , Brian R Kotajarvi  4 , Denise R Lecy  3 , Matthew J Yousefzadeh  5 , Marissa J Schafer  1   6 , Thomas A White  1   2 , Elizabeth J Atkinson  7 , Nathan K LeBrasseur  1   2   6
Affiliations

Exercise reduces circulating biomarkers of cellular senescence in humans

Davis A Englund et al. Aging Cell. 2021 Jul.

Abstract

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.

Keywords: aging; immune cells; inflammation; senotherapeutics.

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Conflict of interest statement

The authors declare no conflicts of interest. ClinicalTrials.gov Identifier: NCT04897373.

Figures

FIGURE 1
FIGURE 1
Twelve weeks of structured exercise improves body composition and physical function in older adults. (a) Study design schematic. (b) Subject characteristics at baseline and follow‐up; measures of body composition were assessed by DEXA scan and self‐reported physical and mental function was captured with the MOS SF‐12. (c) Levels of habitual physical activity before and after the intervention period, as assessed by accelerometry. (d) Clinical measures of physical function and strength before and after the intervention. (e) Self‐reported measures of functional status at baseline and follow‐up, as assessed by a linear analog self‐assessment scale. Results are mean ± SD. *p < 0.05, ****p < 0.0001
FIGURE 2
FIGURE 2
Biomarkers of cellular senescence are predictive of functional adaptation to exercise. (a) Expression of cellular senescence markers in CD3+ T cells at baseline and following the intervention period. (b) Concentrations of circulating senescence‐related proteins before and after the intervention. (c) The PLSDA‐derived index of senescent cell burden differentiates between subjects who showed improvements in the timed up and go measure (responders [blue]) and those who did not (non‐responders [gray]) in response to the intervention. (d) VIP scores, which rank SASP factors on their importance for differentiating between responders (blue) and non‐responders (gray). (e) Predicted and observed change in gait speed using the SASP index. Results are mean ± SD. *p < 0.05, **p < 0.01
See this image and copyright information in PMC

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