The Future of Aging Dr. Kirkland Interview Series Ep 6

In this video Dr. Kirkland talks about the future of aging and how the biology of aging affects everyone and should not be thought of as only relevant to older people. He also discusses the path of bringing senolytics to wider use.

Dr. James Kirkland is Director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic and Noaber Foundation Professor of Aging Research. Dr. Kirkland's research focuses 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 and to extend healthspan. He published the first article about drugs that clear senescent cells, senolytic agents. A novel, mechanism-based, hypothesis-driven drug development paradigm was used to discover senolytic drugs. Based on the observation that senescent cells release factors that cause apoptosis of the cells around them, yet are themselves resistant to apoptosis, Dr. Kirkland hypothesized that senescent cells utilize senescent cell anti-apoptotic pathways (SCAPs) for protection from their own senescence-associated secretory phenotype (SASP). Using bioinformatics analyses of senescent vs. non-senescent cells and RNA interference, Dr. Kirkland identified these SCAPs and verified their importance for senescent cell survival. Dr. Kirkland used bioinformatics approaches to identify agents that target key nodes across the SCAP network and demonstrated these drugs are senolytic in rodent and human cultured cells and mice in vivo. These senolytic drugs include Dasatinib (D), Quercetin (Q), Fisetin, Navitoclax, and related compounds. Dr. Kirkland showed these agents delay, prevent, or alleviate multiple disorders in mouse models of human chronic diseases and aging phenotypes. Conditions alleviated in mouse models include frailty, diabetes, hepatic steatosis, cirrhosis, renal dysfunction, neuropsychiatric disorders, dementias, pulmonary fibrosis, osteoporosis, osteoarthritis, retinal degeneration, diastolic dysfunction, cardiac ischemia, vascular hyporeactivity, infertility, and skin disorders, among others. He demonstrated that intermittent, orally administered senolytics reduce senescent cell abundance in adipose tissue and blood markers of senescent cell burden in blood of patients with diabetic kidney disease. He and collaborators found that a brief course of senolytics enhances physical function and reduces frailty in patients with idiopathic pulmonary fibrosis, a fatal, cellular-senescence-driven disease for which available treatments have been unsatisfactory. Multiple clinical trials are currently underway of the senolytics that Dr. Kirkland discovered. He is a scientific advisory board member for several companies and academic organizations. In addition to being President-Elect of AFAR, he has been a member of the National Advisory Council on Aging of the National Institutes of Health, and past chair of the Biological Sciences Section of the Gerontological Society of America. 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.

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