Interventions that target fundamental aging mechanisms: myths and realities

Fundamental aging processes appear to be the root cause contributors to the chronic diseases that account for the bulk of morbidity, hospital admissions, mortality, and health costs. They may also contribute to causing aging phenotypes, geriatric syndromes (e.g., frailty, sarcopenia, cognitive impairment, falling, and incontinence), and loss of physical resilience (e.g., delayed or prolonged recovery and increased mortality from injury, infection, or surgery, inadequate response to vaccination, and adverse drug reactions), which is the geroscience hypothesis. In this review, we discuss these fundamental aging processes or “hallmarks of aging,” their interconnectedness (the Unitary Theory of Fundamental Aging Mechanisms), and interventions targeting these hallmarks that have been reported, are being tested, or may be developed. Next, we propose ideas about how to intervene at points that would impact different hallmarks of aging simultaneously or sequentially, potentially to achieve additive or synergistic benefits in enhancing health span by delaying, preventing, or alleviating chronic diseases, the geriatric syndromes, aging phenotypes, and/or enhancing physical resilience.