Yi Zhu1,2, Zacharias P. Anastasiadis3, Jair Machado Espindola Netto2, Tamara Evans2, Tamar Tchkonia1,2 and James L. Kirkland1,4 1Department of Physiology and Biomedical Engineering, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA 2Robert and Arlene Kogod Center on Aging, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA 3Department of Biochemistry and Molecular Biology, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA 4Division of General Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA Correspondence: kirkland.jamesmayo.edu

Cellular senescence was initially described in the early 1960s by Hayflick and Moorehead. They noted sustained cell-cycle arrest after repeated subculturing of human primary cells. Over half a century later, cellular senescence has become recognized as one of the fundamental pillars of aging. Developing senotherapeutics, interventions that selectively eliminate or target senescent cells, has emerged as a key focus in health research. In this article, we note major milestones in cellular senescence research, discuss current challenges, and point to future directions for this rapidly growing field.