012 - Individualized health-preservation plans based on dysregulation assessment

Homeostasis is the maintenance of physiologic constancy and the various mechanisms by which living organisms regulate their internal environment. Homeostasis causes operating variables such as glucose level, body temperature, or blood pressure to be maintained close to optimal set points, e.g., Sweet Spots. Homeostatic imbalance occurs when normal physiologic control is disrupted, with aging being a major factor in such dysregulation. The Canadian Institute for Health Information projects an increase in the burden on the healthcare system due to the prevalence of the over-65 age group among Canada's population. This demographical situation raises the importance of discovering of new indicators of homeostenosis, lifestyle factors associated with physiological dysregulation, and further development of preventive policies.
Identifying homeostatically-controlled traits across multiple domains and data sources will extend our knowledge about biological pathways and networks involved in homeostasis of that measures. Examining the genetic effects on distance from each sweet spot will inform insights into genetic architecture of homeostasis in health and may allow re-purposing of known drugs or development of new drugs to preserve the homeostatic condition across the lifespan. A nuanced health report-card for individuals based on deviation from optimal values could predict future health outcomes and motivate to take actions before they are outside of the clinically normal ranges. Further, understanding the lifestyle and socioeconomic factors with effect on phenotypic sweet spot distance would allow development of individualized health-preservation plans.
Studying successful aging allows us to identify previously unrecognized features of healthy aging. The Super Seniors Study recruited healthy oldest-old and population-based mid-life controls to study genetic factors associated with healthy aging. Super Seniors are healthy individuals aged 85–110 who at recruitment had never been diagnosed with cancer, cardiovascular disease, major pulmonary disease, dementia, or diabetes. We previously reported that the group of Super Seniors show reduced telomere length variance compared to the middle-aged group. They also show lower variance in some hematology parameters compared to age-matched less healthy seniors. We hypothesized that the healthier group has physiological measures closer to a Sweet Spot, and therefore lower variance, for traits that are relevant for healthy aging. This study aims to discover new physiologic measures relevant to healthy aging and homeostasis, and lifestyle and genetic factors associated with optimal homeostatic regulation.
We examine data from the Canadian Longitudinal Study on Aging (CLSA), including 30,097 participants aged 45 to 85 years. Physiological variables across eight domains and untargeted plasma metabolomic profiling were used for investigation. Using five instruments, we calculated health scores for CLSA Comprehensive cohort participants. Homogeneity of variance was pairwise tested between the most healthy and least healthy instrument levels. We also characterized the relationship between each instrument and phenotype magnitude using segmented regression to determine sex and age-specific optimal values.
Initial findings validate the proposed approach and underscore the relevance of applying a homeostasis lens to human physiology. In total, 142 physiological measures and 94 metabolites revealed heteroskedasticity. Moreover, a positive association between total dysregulation and health decline confirmed that having a value further from Sweet Spot, in either direction, correlates with greater levels of health deficits. Future work to examine the genetic and lifestyle effects on distance from each sweet spot will inform insights into how to optimize and preserve health.

healthy aging

CLSA

homeostasis

Sweet Spots

health-preservation plans