Aging is the major risk factor for the conditions that account for the bulk of morbidity, mortality, and health costs, including diabetes, frailty and sarcopenia, loss of resilience, dementias and neurodegenerative diseases, lung diseases, many cancers, bone and joint disease, atherosclerosis, and impaired vascular reactivity. Senescent cells are at sites of pathology in these conditions. Interventions that target fundamental aging processes, including genetic or pharmacological targeting of senescent cells or their products, may delay, prevent, or alleviate most of these conditions. Here we discuss the development of drugs that target senescent cells- senolytics – and potential paths to clinical translation, focusing on diabetes and adipose tissue dysfunction.
Upon completion of this activity, participants should be able to:
Describe the relation between fundamental aging mechanisms and age-related chronic diseases and dysfunction
Discuss the emerging role of cellular senescence and senolytic agents
Identify issues about translating agents that affect fundamental aging processes in model organisms into clinical interventions
James L. Kirkland, M.D., Ph.D. is the Director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic and Noaber Foundation Professor of Aging Research. Dr. Kirkland’s research is on cellular senescence, age-related adipose tissue and metabolic dysfunction, and development of agents and strategies for targeting fundamental aging mechanisms to treat age-related chronic diseases and disabilities. He recently published the first article about drugs that clear senescent cells – senolytic agents. He is a scientific advisory board member for several companies and academic organizations. He is a member of the National Advisory Council on Aging of the National Institutes of Health, past chair of the Biological Sciences Section of the Gerontological Society of America, and a member of the Board of the American Federation for Aging Research. He holds honorary appointments at Boston University and the University of Groningen in the Netherlands. He is a board certified specialist in internal medicine, geriatrics, and endocrinology and metabolism.