Multiple theories of aging (e.g., free radical, error catastrophe, mitochondrial) are complementary but fail to provide adequate models that comprehensively predict lifelong aging processes and that are valid across species. Hayflick (PLoS Genet 3(12):2351-2354, 2007) described six universal characteristics of aging that focus upon post-reproductive molecular entropy. Here we present a thermodynamic potential model of aging in which the energetic and topological properties of the mitochondrion drive functional and structural stabilities within living systems. Using multivariate regressions of physiological assessments from the National Health and Nutrition Examination Survey, VO2 max consistently declined with age regardless of gender or race, although it had a significantly greater decline for African American females. Percent fat (negative), hematocrit (negative), and urine creatinine (negative) were strongly and significantly associated with VO2 max and male aging, although cholesterol (positive) was an additional factor for African American males. Bioenergetic measures such as VO2 max can be useful for physical assessments to promote healthy aging.