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AREAS OF SPECIALTY:

  • Senolytics

  • Basic and Translational Geroscience Research

  • Gerodiagnostic Biomarkers

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

  • Cellular Aging, Mayo Clinic

  • Board Member,  American Federation for Aging Research (AFAR)

The major focus of James L. Kirkland, M.D., Ph.D.’s research is the impact of cellular senescence on age-related dysfunction as well as acute and chronic diseases across the lifespan, especially in developing methods to remove these cells and alleviate their effects. Senescent cells accumulate with aging as well as with multiple diseases and disorders throughout life, such as in childhood cancer survivors. The presence of senescent cells accentuates severity and complications of diseases such as dementia, atherosclerosis, cancers, diabetes, and arthritis. Transplanting small numbers of these cells can cause considerable dysfunction in recipients.

The goal of Dr. Kirkland's current work is to develop methods to remove senescent cells in order to delay, prevent, alleviate, or potentially even reverse multiple disorders and diseases throughout life, including loss of ability to recover after injuries, enhancing function of cells or organs to be transplanted, and even agricultural applications.

FOCUS AREAS

  • Cellular Senescence and Senolytics. Work by Dr. N. Sharpless published in 2004 indicated that enhanced healthspan from caloric restriction and other interventions correlates with reduced senescent cell burden. Based on this, to test if removing senescent cells actually alleviates age-related dysfunction, Dr. Kirkland's team began to develop senolytics. Senolytics are a new class of drugs that selectively eliminate tissue-damaging senescent cells. The Kirkland group published the first reported senolytics in 2015 and first demonstrated that reducing senescent cell burden can alleviate dysfunction in naturally aged animals. This gave proof of principle that clearing senescent cells with a drug might be beneficial and led to the first clinical trials of senolytics reported in 2019. There are now over 30 clinical trials of these agents for multiple conditions underway and many laboratories and companies around the world working on senolytics.

aging critical publications

  • Chaib, S., Tchkonia, T., Kirkland, J.L. Cellular senescence and senolytics: The path to the clinic. Nature Medicine 2022 Aug 11. doi.org/10.1038/s41591-022-01923-y. PMID: 35953721 (reviews some of the completed and ongoing clinical trials of senolytics).

  • Justice, J.N., Nambiar, A.M., Tchkonia, T., LeBrasseur, N.K., Pascual, R., Hashmi, S.K., Prata, L., Masternak, M.M., Kritchevsky, S.B., Musi, N., Kirkland, J.L. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. eBioMedicine, 2019. Jan 4. pii: S2352-3964(18)30629-7. doi: 10.1016/j.ebiom.2018.12.052. PMID: 30616998 (first reported clinical trial of senolytics).

  • 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 (fulfills Koch’s postulates: transplanting small numbers of senescent cells causes aging-like dysfunction).

  • Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A., Ding, H., Giorgadze, N., Palmer, A.K., Ikeno, Y., Borden, G., Lenburg, M., O'Hara, S.P., LaRusso, N.F., Miller, J.D., Roos, C.M., Verzosa, G.C., LeBrasseur, N.K., Wren, J.D., Farr, J.N., Khosla, S., Stout, M.B., McGowan, S.J., Fuhrmann-Stroissnigg, H., Gurkar, A.U., Zhao, J., Colangelo, D., Dorronsoro, A., Ling, Y.Y., Barghouthy, A.S., Navarro, D.C., Sano, T., Robbins, P.D., Niedernhofer, L.J., Kirkland, J.L. The Achilles' heel of senescent cells: From transcriptome to senolytic drugs. Aging Cell 14:644-658, 2015. PMID: 25754370 (first report of senolytics and first demonstration that decreasing senescent cell burden in naturally aged mice alleviates dysfunction).