Research questions: Aging can be seen as a gradual increase in disorder, where random fluctuations and noise drive patterns of disruption and loss of function. How to define and measure this disorderness, entropy, in biological systems is not available yet. We hypothesized that homeostatic dysregulation index (HD) derived from multimodal data can be measured to quantify entropy in biological system. If it is a measure of increased entropy associated with aging, this should be associated with various health outcomes including mortality, cardiovascular, musculoskeletal, and neurocognitive events. HD derived from multiple modalities as a measure of entropy in integrated biological systems may improve the discriminatory performance for outcomes compared to single-modal HD or other conventional clinical predictors.
Objectives:
1) Establish concepts and methodology to estimate multimodal homeostatic dysregulation index
2) Examine association between single-modal HD (blood laboratory-based HD, image-derived HDs [whole body MR, DXA hip, spine], ECG-HD, actigraph-HD, genomic-HD) health outcomes
3) Assess correlation among single modal HDs representing various biological systems
4) Assess association of multi-modal HD with physical performance and cognitive function and health outcomes
5) Evaluate the improvement of discriminatory performance by multi-modal HD over single-modal HDs or clinical predictors
Scientific background:
One tool showing promise to measure entropy is homeostatic dysregulation (HD; Cohen, 2013; PMID: 23376244). HD is measured by calculating the Mahalanobis distance, which indicates how far an individual’s set of biomarkers deviates from the population average. This measure highlights the extent of an individual’s biological divergence from typical population patterns. HD calculated using clinical biomarkers showed an increase across aging, which was associated with onset of various comorbidities. (Li Q et al., 2024; PMID: 3731383