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Human genetics has mostly focused on variants that cause or predispose to disease. Identifying genetic variants that keep humans healthy is an equally attractive approach to identify novel drug targets. Two recent studies have highlighted that such endeavors are worthwhile. In a study published in Cell, Erikson et al. performed whole genome sequencing in a cohort of individuals with a healthy aging phenotype defined as >80 years old without chronic diseases or chronic medications, also known as the Wellderly study [1]. The investigators found that healthy aging is associated with reduced genetic susceptibility to Alzheimer (depletion of APOE-ε4 alleles) and coronary artery disease. They also identified one gene of major interest, COL25A1, which contained ultra-rare coding variants in multiple Wellderly individuals. The investigators speculate that mutations in COL25A1 may disrupt Alzheimer disease pathogenesis, which is consistent with their overall finding that healthy aging is associated with genetic resistance to cognitive decline. …