Aging and Allostasis: Using Bayesian Network Analytics to Explore and Evaluate Allostatic Markers in the Context of Aging

Abstract

Allostatic load reflects the cumulative strain on organic functions that may gradually evolve into overt disease. Our aim was to evaluate the allostatic parameters in the context of aging, and identify the parameters that may be suitable for an allostatic load index for elderly people (>60 years). From previously published studies, 11 allostatic (bio)markers could be identified that sustain sufficient variability with aging to capture meaningful changes in health status. Based on reported statistics (prevalence of a biomarker and its associated outcome, and/or an odds/risk ratio relating these two), seven of these could be adopted in a Bayesian Belief Network (BBN), providing the probability of “disturbed” allostasis in any given elder. Additional statistical analyses showed that changes in IL-6 and BMI contributed the most to a “disturbed” allostasis, indicating their prognostic potential in relation to deteriorating health in otherwise generally healthy elderly. In this way, and despite the natural decline in variance that irrevocably alters the prognostic relevance of most allostatic (bio)markers with aging, it appeared possible to outline an allostatic load index specifically for the elderly. The allostatic parameters here identified might consequently be considered a useful basis for future quantitative modelling in the context of (healthy) aging.

Features of Allostatic Load in Patients with Essential Hypertension without Metabolic Syndrome Depending on the Nature of Nighttime Decreases in Blood Pressure

“…Previous studies have also established that allostatic load in patients with EH [19] without metabolic syndrome does not depend on patients' age and can be considered a general characteristic of EH [4]. Taking into account the pathogenetic links between allostatic load and aging [17,18,20,21,37,39,58,62], the increasing number of patients with EH [8,9,63], the possibility of using allostasis indicators to assess the effectiveness of therapy seems to be an urgent issue. The results of our study indicate that focusing only on target levels of BP does not provide an opportunity to reduce allostatic load.…”

“…It's important that the study involved patients receiving antihypertensive therapy that reached the target values. Taking into account the fact that the development of allostasis is commonly accompanied by aging of the body, this problem requires a more thorough investigation [17][18][19][20][21][22].…”

New Possibilities for Evaluating the Development of Age-Related Pathologies Using the Dynamical Network Biomarkers Theory

“…Allostatic load is measurable using an index of biomarkers known as the allostatic load index (ALI) in clinical studies. The ALI is composed of six categories: neuroendocrine function (cortisol, dehydroepiandrosterone, epinephrin, norepinephrine, dopamine, and aldosterone), immune function (IL-6, TNF-alpha, c-reactive protein, and IGF-1), metabolic function (HDL/LDL-cholesterol, triglyceride, glycosylated hemoglobin, blood glucose, insulin, albumin, creatinine, and homocysteine), cardiovascular/respiratory function (systolic blood pressure, diastolic blood pressure, peak expiratory flow, and heart rate), and anthropometric measurements (waist-to-hip ratio and body mass index) [ 136 , 137 ]. It is noteworthy that each allostatic mediator is interconnected in a nonlinear network, and many body systems are influenced by the same mediators [ 138 ].…”

“…Hence, the expression of IL-6 is proposed to serve as an early warning sign for the burden of multimorbidity [ 153 ]. As the level of IL-6 expression is included in ALI [ 136 ], analyzing ALI using the DNB theory will be fascinating to test as a novel methodology for the prediction of age-related loss of resilience, as well as the progression of cellular senescence in humans. Numerous studies have suggested that aging occurs through complex and dynamic changes [ 131 , 132 , 144 , 147 , 148 ].…”

Neutralizing a Springboard for Inflammation: Physical Activity to Control the Immune Network

“…Finally, because (visceral) obesity has convincingly been associated with a state of chronic low-grade inflammation, causing a significant strain on healthy immune functioning [19,20], it may, combined with the impact of chronic psychological stress on the immune system, very well close the toxic vicious circle of psychological stress, metabolic and cardiovascular health, and decreased inflammatory resilience [21] (see Figure 1). Glucocorticoids produced by the Hypothalamic-Pituitary-Adrenal (HPA)-axis seem to play a central role in this precarious equilibrium underlying health and well-being [22]. Consequently, effectively investing in cardiovascular fitness might stimulate some highly relevant positive side effects in immune functioning, either directly and/or indirectly via, for example, its effects on mental well-being.…”