Exercise reduces circulating biomarkers of cellular senescence in humans

Abstract

Cellular senescence is a plausible and potentially tractable mechanism of aging. Molecular hallmarks of senescent cells, including the expression of cyclin-dependent kinase inhibitors (CDKIs), DNA damage-response proteins, and mediators and components of the senescence-associated secretory phenotype (SASP), increase in multiple tissues with advancing age and chronic disease (Tuttle et al., 2020). Indeed, in mice, targeted elimination of senescent cells by genetic approaches and candidate senotherapeutic drugs restores tissue health and attenuates the progression of numerous age-related

Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome

“…Interventions and lifestyle modifications, including increased physical activity, improved dietary patterns, and good management of chronic medical conditions, contribute to improved general health, possibly by regulating different age-related biological processes and slowing of molecular and cellular senescence. 59 , 60 , 61 Importantly, these lifestyle and behavioral factors are protective against the development of depressive symptoms and can be used as adjunctive treatment options to improve treatment response in older adults with major depression, 62 , 63 , 64 but also can be useful for the prevention of other age-related outcomes commonly observed in this population. Finally, geroscience-guided interventions, such as using senolytic drugs that specifically clear senescence cells aiming to reduce or mitigate cellular senescence and the harmful effects of SASP factors, 65 could be used to improve antidepressant treatment outcomes in LLD.…”

Associations Between Plasma Growth and Differentiation Factor-15 with Aging Phenotypes in Muscle, Adipose Tissue, and Bone

“…However, recently, there is compelling evidence that cellular senescence, a state of stable growth arrest caused by diverse forms of cellular and molecular damage, contributes to aging and multiple aging-related dysfunction, in part, through the SASP [22,23]. Circulating mediators of SASP in human, produced by senescent cells, were positively associated with age, frailty, and adverse postsurgical outcomes [18] and were predictive of changes in physical function in response to exercise interventions to improve muscle performance and physical function such as grip strength, repeated sit-to-stand time, and the timed up and go test [24]. These findings suggest that circulating SASP factors serve as a clinically useful candidate biomarker of aging-related dysfunction and a powerful tool for interventional human studies.…”

“…These findings suggest that circulating SASP factors serve as a clinically useful candidate biomarker of aging-related dysfunction and a powerful tool for interventional human studies. GDF-15 is reported to be a member of the SASP group of proteins [18,24], so its level might have potential as a biomarker of aging-related phenotypes of body composition, such as low muscle mass, obesity, and low bone mass.…”

“…First, we only evaluated the association between GDF-15 levels and muscle mass, and not muscle strength or physical performance. However, there are some studies that support a significant association between serum GDF-15 levels and muscle strength or physical performance [7,8,[11][12][13]24]. Second, we used BMI rather than height-adjusted muscle mass in the sarcopenia diagnosis.…”

Nutritional components as mitigators of cellular senescence in organismal aging: a comprehensive review

“…It has long been argued that regular exercise and a healthy diet regimen is key to improving both the healthspan and lifespan. Emerging evidence now suggests that indeed both exercise and a healthy diet (e.g., Mediterranean diet) can improve the indices of general health and longevity through specific targeting of cellular senescence and its deleterious effects (Englund et al, 2021 ; Marin et al, 2012 ; Shannon et al, 2021 ). It is desirable that dietary constituents should be studied individually as well as in combinations of whole diets with a specific aim of identifying nutritional geroprotectors through the purview of cellular senescence that may enable a better pharmacological understanding of nutrition as a regulator of aging and diseases.…”