Plasma proteomic signature of the risk of developing mobility disability: A 9-year follow-up

Yusuke Osawa, Richard D. Semba, Giovanna Fantoni, Julián Candia, Angélique Biancotto, Toshiko Tanaka, Stefania Bandinelli, Luigi Ferrucci

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Introduction: Mobility disability is a powerful indicator of poor health in older adults. The biological and pathophysiological mechanism underlying the development of mobility disability remains unknown. This study conducted a data-driven discovery phase investigation to identify plasma proteins that predict the incidence of mobility disability in community-dwelling older adults without mobility disability at baseline. Methods: We investigated 660 women and men, aged 71.9 ± 6.0 (60–94) years, who participated in the Invecchiare in Chianti, “Aging in the Chianti Area” study and completed the 400-m walk at fast pace (400-m walk) at enrollment. Median follow-up time was 8.57 [interquartile, 3.20–9.08] years. SOMAscan technology was used to measure 1,301 plasma proteins at enrollment. The incident of mobility disability was defined as inability to complete the 400-m walk. Protein-specific Cox proportional hazard model was adjusted for sex, age, and other important covariates. Results: Plasma levels of 75 proteins predicted mobility disability (p '.05). Significant proteins were enriched for the KEGG “PI3K-Akt signaling,” “phagosomes,” and “cytokine–cytokine receptor interaction” pathways. After multiple comparison adjustment, plasma cathepsin S (CTSS; hazard ratio [HR] 1.33, 95% CI: 1.17, 1.51, q = 0.007), growth/differentiation factor 15 (GDF15; HR: 1.45, 95% CI: 1.23, 1.72, q = 0.007), and thrombospondin-2 (THBS2; HR: 1.44, 95% CI: 1.22, 1.69, q = 0.007) remained significantly associated with high risk of losing mobility. Conclusion: CTSS, GDF15, and THBS2 are novel blood biomarkers associated with new mobility disability in community-dwelling individuals. Overall, our analysis suggests that cellular senescence and inflammation should be targeted for prevention of mobility disability.

Original languageEnglish (US)
Article numbere13132
JournalAging Cell
Issue number4
StatePublished - Apr 1 2020


  • cathepsin S
  • growth/differentiation factor 15
  • mobility disability
  • proteomics
  • thrombospondin-2

ASJC Scopus subject areas

  • Aging
  • Cell Biology


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