Longitudinal associations of platelet activation phenotypes with frailty and physical performance in older adults living at high southern latitudes

<title>Abstract</title> <p> Background Aging is accompanied by chronic low-grade inflammation, altered platelet biology, and progressive vulnerability to adverse health outcomes. Platelet activation has been proposed as a potential biomarker of immunothrombotic aging, but longitudinal evidence linking platelet phenotypes with frailty and physical performance in older adults remains limited. This study examined the longitudinal associations of resting and activated platelet phenotypes with frailty and physical performance in community-dwelling older adults living at high southern latitudes. Methods A total of 137 older adults from Punta Arenas, Chile, were assessed across three time points over one year. Platelet phenotypes were characterized by flow cytometry based on CD41 and CD62 expression, distinguishing resting CD41 ⁺ /CD62 ⁻ and activated CD41 ⁺ /CD62 ⁺ platelet populations. Frailty was assessed using the FRAIL scale, and physical performance was evaluated through handgrip strength (HGS), chair sit-to-stand (CSTS), arm curl, and timed up-and-go (TUG) tests. Bayesian multilevel models were used to estimate longitudinal associations while accounting for repeated measurements and adjusting for age, sex, and body mass index (BMI). Results Frailty scores remained relatively stable over time, whereas platelet phenotype distributions showed clear temporal changes, particularly a decline in the CD41 ⁺ /CD62 ⁻ platelet population. Higher BMI was consistently associated with greater frailty. Platelet phenotypes showed modest and uncertain associations with frailty, CD41 ⁺ /CD62 ⁻ tending toward a protective association. In contrast, higher proportions of CD41 ⁺ /CD62 ⁺ and CD41 ⁺ /CD62 ⁻ platelets were associated with better physical performance, particularly in CSTS, arm curl, and TUG outcomes. Conclusions Platelet activation phenotypes may provide useful biological information about functional aging trajectories in older adults. Although associations with frailty were modest, the relationship between platelet phenotypes and physical performance suggests that platelet biology may reflect aspects of physiological reserve. These findings should be interpreted as exploratory and require replication in larger cohorts incorporating inflammatory, pharmacological, and environmental measures. </p>