Center for Cardiovascular and Muscular Diseases CCMD
Distinguished Cardiovascular and Muscular Diseases Seminar Series
Speaker
James L. Kirkland, MD, PhD
Professor of Medicine and Director
Center for Advanced Gerotherapeutics
Cedars-Sinai Medical Center
Seminar Abstract: Cellular senescence is a cell fate entailing essentially irreversible replicative arrest and resistance to apoptosis that can occur in most cell types across the age range in response to damage-related signals. Senescent cells can acquire a senescence-associated secretory phenotype that includes release of multiple proteins, peptides, bioactive small molecules, and coding and non-coding nucleotides. Persisting senescent cells not removed by the immune system can become pro-inflammatory, spread senescence locally and systemically, release aggregated proteins, reshape the extracellular matrix, and sometimes escape senescence to emerge as cancer cells. Transplanting senescent cells or organs containing senescent cells can induce multiple disorders and diseases. Conversely, senolytics, agents that selectively eliminate pro-inflammatory senescent cells, appear to delay, prevent, alleviate, or treat multiple conditions in preclinical models. Clinical trials of senolytics are currently underway, with some indicating safety, tolerability, and target engagement and with a few early phase clinical trials suggesting efficacy. Much remains to be done to determine if senolytics will enter clinical practice.