"Physiological Dysregulation" as a Promising Measure of Robustness and Resilience in Studies of Aging and a New Indicator of Preclinical Disease

Abstract

Recently suggested novel implementation of the statistical distance measure (DM) for evaluating "physiological dysregulation" (PD) in aging individuals (based on measuring deviations of multiple biomarkers from baseline or normal physiological states) allows reducing high-dimensional biomarker space into a single PD estimate. Here we constructed DM using biomarker profiles from FRAMCOHORT (Framingham Heart Study) and CHS (Cardiovascular Health Study) Research Materials obtained from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center, and estimated effect of PD on total survival, onset of unhealthy life (proxy for "robustness") and survival following the onset of unhealthy life (proxy for "resilience"). We investigated relationships between PD and declines in stress resistance and adaptive capacity not directly observed in data. PD was more strongly associated with the onset of unhealthy life than with survival after disease suggesting that declines in robustness and resilience with age may have overlapping as well as distinct mechanisms. We conclude that multiple deviations of physiological markers from their normal states (reflected in higher PD) may contribute to increased vulnerability to many diseases and precede their clinical manifestation. This supports potential use of PD in health care as a preclinical indicator of transition from healthy to unhealthy state.

Keywords: Biodemography; Biomarkers; Health; Longevity; Mahalanobis distance.

Figure 1.

Average age-trajectories of physiological dysregulation (represented by D_M) for longer- vs shorter-lived study participants: (A) females in FRAMCOHORT; (B) females in CHS; (C) males in FRAMCOHORT; (D) males in CHS. Each trajectory presents average values (±SE) of D_M in 10-y age intervals for individuals dying at different ages shown in the legend (“50–59” to “80–89”) or surviving until age 90 (“≥90”).