Optimizing Translational Research for Exceptional Health and Life Span: A Systematic Narrative of Studies to Identify Translatable Therapeutic Target(s) for Exceptional Health Span in Humans

Background: Exceptional longevity as manifested by the lower incidence and delayed onset of age-related disabilities/diseases that include cardiovascular disease, Alzheimer's disease, cancer is believed to be influenced by inherent protective molecular factors in exceptionally long-lived individuals. Unraveling these protective factors could lead to the discovery of therapeutic target(s) and interventions to promote healthy aging. Methods: In this context, the National Institute on Aging has established a collection of translational longevity research projects (ie, the Long-Life Family Study, the Longevity Consortium, Longevity Genomics, and the Integrative Longevity Omics) which are generating large omics data sets spanning the human genome to phenome and have embarked on cross-species multiomic data analyses integrating human and nonhuman species that display wide variation in their life spans. Results: It is expected that these studies will discover key signaling pathways that influence exceptional health span and identify therapeutic targets for translation to enhance health and life span. Other efforts related to translational longevity research include the "Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins study,"which focuses on potential effects in humans of polypeptides/proteins whose circulating levels change with age, and for which experimental evidence indicates reversal or acceleration of aging changes. The "Predictive Human Mechanistic Markers Network"is devoted to the development of predictive markers of aging, for target engagement when testing novel interventions for healthy aging. Conclusion: We describe here the significance, the unique study design, categories of data sets, analytical strategies, and a data portal to facilitate open science and sharing of resources from these longevity studies to identify and validate potential therapeutic targets for healthy aging.