TY - JOUR
T1 - Associations between biomarkers of cellular senescence and physical function in humans
T2 - observations from the lifestyle interventions for elders (LIFE) study
AU - Fielding, Roger A.
AU - Atkinson, Elizabeth J.
AU - Aversa, Zaira
AU - White, Thomas A.
AU - Heeren, Amanda A.
AU - Achenbach, Sara J.
AU - Mielke, Michelle M.
AU - Cummings, Steven R.
AU - Pahor, Marco
AU - Leeuwenburgh, Christiaan
AU - LeBrasseur, Nathan K.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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 1377 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-m 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 ≤ 7). Senescence biomarkers were also associated with lower grip strength, and GBM identified PARC, ADAMTS13, and RANTES as top candidates in females, and MMP2, SOST, and MCP1 in males. These findings highlight an association between senescence biomarkers and physical performance in older adults. ClinicalTrials.gov Identifier: NCT01072500.
AB - 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 1377 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-m 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 ≤ 7). Senescence biomarkers were also associated with lower grip strength, and GBM identified PARC, ADAMTS13, and RANTES as top candidates in females, and MMP2, SOST, and MCP1 in males. These findings highlight an association between senescence biomarkers and physical performance in older adults. ClinicalTrials.gov Identifier: NCT01072500.
KW - Aging
KW - Biomarkers
KW - Frailty
KW - Physical function
KW - Sarcopenia
KW - Short physical performance battery
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U2 - 10.1007/s11357-022-00685-2
DO - 10.1007/s11357-022-00685-2
M3 - Article
C2 - 36367600
AN - SCOPUS:85141706547
SN - 2509-2715
VL - 44
SP - 2757
EP - 2770
JO - GeroScience
JF - GeroScience
IS - 6
ER -