Abstract
Within human physiology, systemic interactions couple physiological variables to maintain homeostasis. These interactions change according to health status and are modified by factors such as age and sex. For several physiological processes, sex-based distinctions in normal physiology are present and defined in isolation. However, new methodologies are indispensable to analyze system-wide properties and interactions with the objective of exploring differences between sexes. Here we propose a new method to construct complex inferential networks from a normalization using the clinical criteria for health of physiological variables, and the correlations between anthropometric and blood tests biomarkers of 198 healthy young participants (117 women, 81 men, from 18 to 27 years old). Physiological networks of men have less correlations, displayed higher modularity, higher small-world index, but were more vulnerable to directed attacks, whereas networks of women were more resilient. The networks of both men and women displayed sex-specific connections that are consistent with the literature. Additionally, we carried out a time-series study on heart rate variability (HRV) using Physionet’s Fantasia database. Autocorrelation of HRV, variance, and Poincare’s plots, as a measure of variability, are statistically significant higher in young men and statistically significant different from young women. These differences are attenuated in older men and women, that have similar HRV distributions. The network approach revealed differences in the association of variables related to glucose homeostasis, nitrogen balance, kidney function, and fat depots. The clusters of physiological variables and their roles within the network remained similar regardless of sex. Both methodologies show a higher number of associations between variables in the physiological system of women, implying redundant mechanisms of control and simultaneously showing that these systems display less variability in time than those of men, constituting a more resilient system.
Highlights
The integration of the physiological systems that conform the human body and its operation can be considered an open structure with characteristics of a complex system that are the result of the large number of system components that comprise it, and the coupling and interactions between them (Bashan et al, 2012)
This relationship is not associated with blood pressure, but is due to the fact that cardiac output is inversely proportional to neuromuscular sympathetic activity (NSA) and total peripheral resistance (TPR)
We found that for men urea levels are correlated with Body mass index (BMI) and related anthropometric indicators but not for women, being both young healthy subjects that have urea, creatinine, and Estimated glomerular filtration rate (eGFR) within the normal range (Figures 6, 8)
Summary
The integration of the physiological systems that conform the human body and its operation can be considered an open structure with characteristics of a complex system that are the result of the large number of system components that comprise it, and the coupling and interactions between them (Bashan et al, 2012). The non-linear interaction of these components, their selforganization, emergent behavior, scale invariance, in addition to their adaptability, support the functional balance required for life (Rivera et al, 2020). By “sex” we refer to “the classification as male or female according to reproductive organs and functions assigned by the chromosomal complement” (Institute of Medicine (US) Committee on Understanding the Biology of Sex and Gender Differences, 2001). The expression of this sexual differentiation produces changes in many organ systems and across the lifespan of the individual, influencing how our bodies interact with the environment to determine health (Rich-Edwards et al, 2018). Sex is recognized as a genetic modifier of disease pathophysiology, resulting in variations which should be considered in the biomedical enterprise (Mauvais-Jarvis et al, 2020)
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