There is a paucity of knowledge from population data about sex differences and their age variation in physiological determinants of longevity. This study fills this gap using nationally representative samples of 38,000 individuals aged 17+ from the National Health and Nutrition Examination Survey (1988-2006). It examines 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 allostatic load. Statistical analyses show substantial sex differences, age variations, and sex by age interaction effects for all variables examined. These patterns remain robust after adjustment of risk factors and shed light on the biological base of the reduction of sex difference in mortality in the post-reproductive life span.