INTERVENTIONS TARGETING CELLULAR SENESCENCE: THE PATH TO TRANSLATION

INTERVENTIONS TARGETING CELLULAR SENESCENCE(definition): THE PATH TO TRANSLATION J. Kirkland, Mayo Clinic, Rochester, Minnesota Aging is the major risk factor for the chronic diseases that account for the bulk of morbidity, mortality, and health costs, including diabetes, frailty, sarcopenia, loss of resilience, dementias, neurodegenerative diseases, lung diseases, many cancers, bone and joint disease, atherosclerosis, and impaired vascular reactivity. Cellular senescence is a cell fate induced by potentially oncogenic insults, inflammation, or metabolic signals. Senescent cells accumulate in multiple tissues with aging and at sites of pathology in age-related chronic diseases. Senescent cells can be eliminated using genetic or pharmacological interventions –senolytic drugs– or their pro-inflammatory senescence-associated secretory phenotype (SASP) alleviated using SASP-inhibitors. Agents that target senescent cells or their products reduce age- and senescence-related dysfunction in vitro and in vivo as well as multiple chronic disease phenotypes in mice. Senolytics(definition) and SASP-inhibitors may one day be translated into clinical use to delay, prevent, or alleviate many of the major age-related chronic diseases in humans.