The Way Forward: Translation

Abstract

Chronological age is the largest risk factor for most of the age-related diseases that account for the bulk of morbidity, mortality, and health costs in developing and developed countries. These disorders, including dementias, atherosclerosis, diabetes, cancers, and arthritis among many others, share predisposing pathogenic mechanisms with processes associated with aging, including low-grade “sterile” inflammation, cellular senescence, accumulation of damaged macromolecules, and stem and progenitor cell dysfunction. These processes are the targets of many of the genetic, environmental, and pharmacological interventions that appear to be effective in extending lifespan in lower mammals. Early indications suggest these interventions may also impact healthspan and resilience, and delay age-related disorders in animal models. Because fundamental aging mechanisms are frequently conserved across a wide range of species, these interventions may be translatable into clinical treatments to prevent, delay, alleviate, or reverse a range of age-related chronic disorders in humans. A great deal of effort to complete the preclinical, clinical proof-of-concept, and formal clinical trials acceptable to regulatory agencies will be required for this to be achieved. Here, we consider some of the interventions that hold promise, the process of translating them into clinical applications, potential clinical conditions for which agents that target fundamental aging mechanisms may be first tested, personnel and resources needed to do so, and regulatory and intellectual property issues in developing feasible interventions. Although the path to clinical application of agents that target fundamental aging mechanisms will likely be difficult, tortuous, and possibly lengthy, the potential to transform health care as we know it is unparalleled.