Characterization of Dynamic Adaptation to Stressors Using Multisystem Stimulus-Response Data: The Study of Physical...

Resilience to stressors has emerged as a major gerontological concept aiming to promote more positive outcomes for older adults. Achieving this aim relies on determining mechanisms underlying the capacity to respond resiliently. This article seeks proof of principle for the hypothesis that physical aspects of said capacity are rooted in the fitness of one's physiology governing stress response, conceptualized as a dynamical system. The Study of Physical Resilience in Aging ("SPRING") leveraged stimulus-response experiments to characterize physiological fitness in older adults scheduled for 1 of 3 major stressors: total knee replacement, incident hemodialysis, or bone marrow transplant in hematological cancer. Here we analyze Holter monitor time series characterizing heart rate variability (HRV), cortisol responses to adrenocorticotropic hormone (ACTH) stimulation, and repeated diurnal salivary cortisol assessment in the SPRING pilot (n = 79). Principal component analysis was applied anticipating steady-state and "adaptation" mechanisms underlying the repeated physiological measures. Analytic features evidenced these mechanisms, supporting construct validity. Component scores were analyzed by major stressor, hypothesized surrogate physiological measures (physical frailty phenotype, self-report of health), and demographic, health, and behavioral characteristics. Scores differed substantially by stressor type and the surrogate physiological measures, evidencing criterion validity. Our data support that HRV, ACTH, and salivary cortisol stimulus-response data jointly assess adaptation capacity across 3 major stressors. We believe that SPRING is the first study in humans to concurrently query multiple physiological systems using stimulus-response tests. Our findings lay groundwork for future validation with further data and to better forecast resilience of older adults to clinical stressors.