Associations between biomarkers of cellular senescence and physical function in humans: Observation from the lifestyle interventions for elders (life) study

Authors: FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ATKINSON, ELIZABETH - Mayo Clinic; AVERSA, ZAIRA - Mayo Clinic; WHITE, THOMAS - Mayo Clinic; HEEREN, AMANDA - Mayo Clinic; ACHENBACH, SARA - Mayo Clinic; MIELKE, MICHELLE - Wake Forest School Of Medicine; CUMMINGS, STEVEN - University Of California San Francisco (UCSF); PAHOR, MARCO - University Of Florida; LEEUWENBURGH, CHIRSTIAAN - University Of Florida; LEBRASSEUR, NATHAN - Mayo Clinic

Submitted to: Nature Aging
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/30/2022
Publication Date: 11/11/2022
Citation: Fielding, R.A., Atkinson, E.J., Aversa, Z., White, T.A., Heeren, A.A., Achenbach, S.J., Mielke, M.M., Cummings, S.R., Pahor, M., Leeuwenburgh, C., Lebrasseur, N.K. 2022. Associations between biomarkers of cellular senescence and physical function in humans: Observation from the lifestyle interventions for elders (life) study. Nature Aging. https://doi.org/10.1007/s11357-022-00685-2.
DOI: https://doi.org/10.1007/s11357-022-00685-2

Interpretive Summary: Cellular senescence is a process related to the aging of many cells in our bodies and may be associated with the decline in walking speed and other measures of physical functioning and strength. ARS-funded researchers in Boston, Massachusetts together with scientists at Mayo Clinic in Rochester Minnesota examined associations between markers of cellular senescence in the blood and measures of physical function and muscle strength in older adults from the Lifestyle Interventions and Independence for Elders Study (LIFE). They observed significant associations between many of the blood markers and a person's physical function. These findings highlight the association between senescence factors, physical performance, and muscle strength and future studies should examine whether cellular senescence can be modulated through diet and physical activity interventions.

Technical Abstract: Cellular senescence is a plausible mediator of age-associated declines in physical performance. To test this premise, we examined cross-sectional associations between circulating components of the senescence-associated secretory phenotype (SASP) and measures of physical function and muscle strength in 1,377 older adults. We showed significant associations between multiple SASP proteins and the short physical performance battery (SPPB), its subcomponents (gait speed, balance, chair rise time), and 400-meter walk time. Activin A, ICAM1, MMP7, VEGFA, and eotaxin showed strong associations based on gradient boost machine learning (GBM), and, when combined with other proteins, effectively identified participants at the greatest risk for mobility disability (SPPB score