James L. Kirkland, M.D., Ph.D.

Cellular Aging, Mayo Clinic

The major research focus of James L. Kirkland, M.D., Ph.D., is the impact of cellular aging (senescence) on age-related dysfunction and chronic diseases, especially developing methods for removing these cells and alleviating their effects. Senescent cells accumulate with aging and in such diseases as dementias, atherosclerosis, cancers, diabetes and arthritis.

The goal of Dr. Kirkland's current work is to develop methods to remove these cells to delay, prevent, alleviate or partially reverse age-related chronic diseases as a group and extend health span, the period of life free of disability, pain, dependence and chronic disease.

Dr. Kirkland's work is important in developing methods to enhance health span and delay onset of the chronic age-related diseases as a group, rather than one at a time. These conditions, including diabetes, dementias, atherosclerosis, cancers and arthritis, among others, account for the bulk of morbidity, mortality and health costs in most of the world.

FOCUS AREAS

  • Cellular senescence. Dr. Kirkland's team developed the idea that removing senescent cells may enhance health span, partly based on the observation that mice with mutations that increase life span have lower senescent cell burden than normal mice, and that short-lived mice have more of these cells. To test this idea, Dr. Kirkland and his team, in collaboration with others at Mayo Clinic, eliminated senescent cells from genetically modified mice, in which a drug-activated "suicide" gene was expressed only in senescent cells. They found that this process enhanced health span, at least in the context of an accelerated aging-like disease. This gave proof of principle for the notion that clearing senescent cells with a drug in non-genetically-modified individuals might be beneficial. They continue to work on developing interventions that selectively target senescent cells.

  • Diabetes, other chronic diseases and cellular senescence. Diabetes and obesity are associated with accumulation of senescent cells in fat and other tissues. Dr. Kirkland's group is working on ways to reduce severity and alleviate the complications of diabetes by clearing senescent cells or blocking them from producing factors that cause or exacerbate dysfunction. Effects of eliminating senescent cells or the factors they release are being investigated on frailty and a range of other chronic disorders in Dr. Kirkland's laboratory and with collaborators at Mayo and other institutions.

aging critical publications

  • Tchkonia T, Kirkland JL. Aging, Cell Senescence, and Chronic Disease: Emerging Therapeutic Strategies. JAMA. 2018 Oct 2; 320 (13):1319-1320

  • Xu M, Pirtskhalava T, Farr JN, Weigand BM, Palmer AK, Weivoda MM, Inman CL, Ogrodnik MB, Hachfeld CM, Fraser DG, Onken JL, Johnson KO, Verzosa GC, Langhi LGP, Weigl M, Giorgadze N, LeBrasseur NK, Miller JD, Jurk D, Singh RJ, Allison DB, Ejima K, Hubbard GB, Ikeno Y, Cubro H, Garovic VD, Hou X, Weroha SJ, Robbins PD, Niedernhofer LJ, Khosla S, Tchkonia T, Kirkland JL. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018

  • Fuhrmann-Stroissnigg H, Ling YY, Zhao J, McGowan SJ, Zhu Y, Brooks RW, Grassi D, Gregg SQ, Stripay JL, Dorronsoro A, Corbo L, Tang P, Bukata C, Ring N, Giacca M, Li X, Tchkonia T, Kirkland JL, Niedernhofer LJ, Robbins PD. Identification of HSP90 inhibitors as a novel class of senolytics. Nat Commun. 2017 Sep 4;