BACKGROUND: Identification of gene variants that contribute to exceptional survival may provide critical biologic information that informs optimal health across the life span. METHODS: As part of phenotype development efforts for the Long Life Family Study, endophenotypes that represent exceptional survival were identified and heritability estimates were calculated. Principal components (PCs) analysis was carried out using 28 physiologic measurements from five trait domains (cardiovascular, cognition, physical function, pulmonary, and metabolic). RESULTS: The five most dominant PCs accounted for 50% of underlying trait variance. The first PC (PC1), which consisted primarily of poor pulmonary and physical function, represented 14.3% of the total variance and had an estimated heritability of 39%. PC2 consisted of measures of good metabolic and cardiovascular function with an estimated heritability of 27%. PC3 was made up of cognitive measures (h(2) = 36%). PC4 and PC5 contained measures of blood pressure and cholesterol, respectively (h(2) = 25% and 16%). CONCLUSIONS: These PCs analysis-derived endophenotypes may be used in genetic association studies to help identify underlying genetic mechanisms that drive exceptional survival in this and other populations.