Sex differences in age trajectories of physiological dysregulation: inflammation, metabolic syndrome, and allostatic load

Yang Yang, University of Chicago
Michael Kozloski, University of Chicago

There is a paucity of knowledge from population data about sex differences and their age variation in physiological determinants of longevity. Using nationally representative samples of 38,000 individuals aged 17+ from the National Health and Nutrition Examination Survey (1988 – 2006), this study provides population based evidence for the potential physiological pathways through which age changes in sex mortality gaps occur. It examined sex differences in the age trajectories of 14 markers of physiological functions across multiple systems and three summary indices including inflammation burden, metabolic syndrome, and cumulative burden of physiological dysregulation indicated by allostatic load. Both descriptive and multivariate analyses show substantial sex differences, age variation, and sex by age interaction effects for all variables examined. Nonlinear and mostly quadratic age patterns of change in these biological variables indicate increasing risks that level off at older ages. The patterns of sex and age differences vary by biological functions. Women exhibit more inflammation and allostatic load, but less metabolic disorders on average than men. The female excess in inflammation decreases in older ages. And female cardiovascular and metabolic advantages decrease and disadvantage in allostatic load increases after menopause. These patterns are highly consistent with the persistent sex difference in survival and the reduction of this difference in all-cause and CVD mortality with age. Differential exposures and vulnerabilities to social behaviors, especially obesity and cigarette smoking, partially account for the sex differences in age patterns of various biological functions. A considerable amount of sex and age variation in most physiological parameters is unexplained, however, emphasizing the need for further investigations of the sex-specific biological mechanisms as well as additional social factors underlying vascular inflammatory, metabolic, and frailty processes across the life course.