Life expectancy has increased by three decades since the mid-twentieth century. Parallel healthspan expansion has however not followed, largely impeded by the pandemic of chronic diseases afflicting a growing older population. The lag in quality of life is a recognized challenge that calls for prioritization of disease-free longevity. Contemporary communal, clinical and research trends aspiring to extend the health horizon are here outlined in the context of an evolving epidemiology. A shared action integrating public and societal endeavors with emerging interventions that target age-related multimorbidity and frailty is needed. A multidimensional buildout of a curative perspective, boosted by modern anti-senescent and regenerative technology with augmented decision making, would require dedicated resources and cost-effective validation to responsibly bridge the healthspan-lifespan gap for a future of equitable global wellbeing.

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Stem cell paracrine activity is implicated in cardiac repair. Linkage between secretome functionality and therapeutic outcome was here interrogated by systems analytics of biobanked human cardiopoietic cells, a regenerative biologic in advanced clinical trials. Protein chip array identified 155 proteins differentially secreted by cardiopoietic cells with clinical benefit, expanded into a 520 node network, collectively revealing inherent vasculogenic properties along with cardiac and smooth muscle differentiation and development. Next generation RNA sequencing, refined by pathway analysis, pinpointed miR-146 dependent regulation upstream of the decoded secretome. Intracellular and extracellular integration unmasked commonality across cardiovasculogenic processes. Mirroring the secretome pattern, infarcted hearts benefiting from cardiopoietic cell therapy restored the disease proteome engaging cardiovascular system functions. The cardiopoietic cell secretome thus confers a therapeutic molecular imprint on recipient hearts, with response informed by predictive systems profiling.