Exercise Decreases Circulating Senescence Proteins

The inflammatory molecules caused by senescent cells are notably decreased by regular exercise.


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A new study published in Aging Cell shows that a 12-week program of structured exercise lowers the activity of the inflammatory SASP in people in their mid-60s.

The expected results

To begin the study, participants were measured, weighed, tested on physical abilities, and asked about their quality of life. They then spent a week wearing accelerometers before engaging in a 12-week program of both strength and endurance training, after which they were measured once more and retained their accelerometers for another week.

To little surprise, this exercise program improved the health of the people who partook in it. Participants enjoyed a roughly 1-kilogram loss in fat mass and an almost 2-centimeter decrease in waist circumference, and both physical and mental composite scores increased slightly. Lean mass was also shown to increase very slightly, although this result was not statistically signfiicant.

Interestingly, the baseline activity of the participants did not change after these 12 weeks. People who were sedentary before the intervention remained sedentary afterwards, as measured by their accelerometers.

The decrease of the SASP

Multiple biomarkers associated with the SASP were shown to decrease after this intervention. CD3(+) T cells expressed less of multiple senescence-related genes, including the well-known p16, p21, and TNF-alpha. Ten different proteins related to cellular senescence were also shown to decrease. While the effect was modest, it was statistically significant and broad in scope.


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Responders and non-responders

Unfortunately, this intervention did not work on everyone, and the timed up-and-go (TUG) test, which measures how quickly someone can get up, walk, and sit back down again, was used to differentiate people who responded from people who did not. Several SASP biomarkers, some more than others, were correlated with the TUG results. People who were shown to have physically benefited from this intervention were also shown to have reduced their circulating SASP; people who were generally unaffected also had their SASP generally unaffected.

While it is inconclusive as to cause and effect, this result strongly links the decrease of the SASP with the benefits of exercise in older people.


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 TNFa, 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.


While this study went in-depth in its analyses, it only had 34 participants and did not have a control group. For an exercise study, the lack of a control group is less important than in many other studies, as it is impossible to engage in vigorous placebo exercise. While it is possible that the self-reported results were brought about by the placebo effect, this cannot meaningfully explain the weight loss, physical improvements, and SASP decrease experienced by the people who benefited from this regimen.

The SASP and other biomarkers of aging do not significantly, spontaneously decrease in aged individuals. Therefore, people looking to achieve longevity should seek safe and proven interventions that decrease these biomarkers, reduce the effects of biological aging, and improve their health.

In this case, the intervention is something that is very inexpensive and available to nearly everyone. While few people can afford personal trainers and many seniors have their exercise options limited due to other effects of aging (such as osteoporosis), regular exercise has repeatedly been shown to improve human health, even in the elderly. This study simply sheds light on some of the reasons why this happens and a potential biomarker-based method for determining whether or not any given exercise program is working as intended.


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The researchers state the most crucial fact as follows:

Exercise remains the most promising intervention to improve physical function in older adults.

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About the author
Josh Conway

Josh Conway

Josh is a professional editor and is responsible for editing our articles before they become available to the public as well as moderating our Discord server. He is also a programmer, long-time supporter of anti-aging medicine, and avid player of the strange game called “real life.” Living in the center of the northern prairie, Josh enjoys long bike rides before the blizzards hit.