Discovering the genetic origin of aging-related traits could greatly advance strategies aiming to extend health span. The results of genome-wide association studies (GWAS) addressing this problem are controversial, and new genetic concepts have been fostered to advance the progress in the field. A limitation of GWAS and new genetic concepts is that they do not thoroughly address specifics of aging-related traits. Integration of theoretical concepts in genetics and aging research with empirical evidence from different disciplines highlights the conceptual problems in studies of genetic origin of aging-related traits. To address these problems, novel approaches of systemic nature are required. These approaches should adopt the non-deterministic nature of linkage of genes with aging-related traits and, consequently, reinforce research strategies for improving our understanding of mechanisms shaping genetic effects on these traits. Investigation of mechanisms will help determine conditions that activate specific genetic variants or profiles and explore to what extent these conditions that shape genetic effects are conserved across human lives and generations.