James L. Kirkland, M.D., Ph.D.
Cellular Aging, Mayo Clinic
The major focus of James L. Kirkland, M.D., Ph.D.’s research is the impact of cellular senescence on age-related dysfunction and chronic diseases, especially in developing methods to remove these cells and alleviate their effects. Senescent cells accumulate with aging and their presence accelerates the severity of diseases such as dementia, atherosclerosis, cancers, diabetes and arthritis.
The goal of Dr. Kirkland's current work is to develop methods to remove senescent cells in order to delay, prevent, or partially reverse age-related chronic diseases as a whole and to extend health span.
Cellular Senescence. Dr. Kirkland's team has found that, removing senescent cells may enhance health span. To test this idea, Dr. Kirkland, 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 that clearing senescent cells with a drug in non-genetically-modified individuals might be beneficial.
Diabetes and other chronic diseases. Diabetes and obesity are associated with accumulation of senescent cells in fat and other tissues. Dr. Kirkland's group is working on ways to alleviate the complications of diabetes by clearing senescent cells or blocking them from producing factors that cause or exacerbate dysfunction.
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;