Yuji Ikeno, M.D., Ph.D.

Over the past 25 years, I have been directly responsible for the pathological analyses of all animals studied in multiple Program Projects and the San Antonio Nathan Shock Aging Center. In addition to pathological analyses of aging animals, I also have multiple research projects that seek the underlying mechanisms of aging. The primary goal of my research is to test whether changes in oxidative stress and redox status in the cell attenuate aging and age-related pathology, e.g., cancer, obesity, and type-2 diabetes, using unique animal models with altered levels of various antioxidant enzymes, e.g., thioredoxin transgenic/knockout mice, Cu/ZnSOD transgenic rats.

Related Diseases: Cancer, obesity, Type 2 DM

• Professional Background

  Education

  • 1993 - PhD - Medicine/Pathology - Nagasaki University School of Medicine
  • 1987 - MD - Medicine - Nagasaki University School of Medicine

  Appointments

  • 9/2016 - Professor - , Barshop Institute
  • 9/2013 - Associate Professor with tenure - UTHSCSA, Department of Pathology, San Antonio
  • 1/2011 - Research Health Scientist - GRECC, South Texas Veterans Health Care System, Audie L. Murphy Division
  • 9/2007 - Project Pathologist - National Institutes of Health, NIA Interventions Testing Program, San Antonio
  • 9/2004 - Pathologist - Contractor - National Institutes of Health, NIA - Primate Aging Study, Lab of Experimental Gerontology, Bethesda
  • 6/2000 - Research Health Scientist - South Texas Veterans Health Care System, Audie L. Murphy Division, Research Services, San Antonio
  • 7/1997 - Director - Nathan Shock Pathology Core - UTHSCSA, Department of Barshop InstituteSan Antonio

• Instruction & Training

  • 5/2010 - Present, Membership on Supervising Committee, The University of Texas Health Science Center at San Antonio
  • 1/2010 - Present, Membership on Supervising Committee, Drexel University

• Research & Grants

  Over the past 25 years, I have been directly responsible for the pathological analyses of all animals studied in multiple Program Projects and the San Antonio Nathan Shock Aging Center.

  Research profile

  Grants

  Federal

  Funding Agency NIH/NIA Title NIH/NIA Targeting Cellular Senescence to Extend Healthspan Status Active Period 6/2019 - 1/2024 Role Principal Investigator Grant Detail The aims are to: 1) To conduct comprehensive pathological analyses of genetically- and/or pharmacologically-manipulated mice/rats and their control animals in the aging colonies; 2) To conduct cellular senescence characterization, histopathological, immunohistochemical, and morphometric analyses of tissues obtained from genetically- and/or pharmacologically-manipulated mice/rats and their control animals in the aging colonies at a specific age point; and 3) To develop a comprehensive database of histopathological findings and a tissue and digital image archive, and to provide histology services as a resource for the analysis of samples by special request and for new morphological research. (PI: J. Kirkland and S. Khosla) Funding Agency NIH/NIA Title NIH/NIA Effect of Aging on Preadipocyte Differentiation Status Active Period 4/2016 - 3/2021 Role Co-Investigator Grant Detail The aims are to: 1) delineate mechanisms and effects of targeting senescent cells in vitro, 2) test effectiveness of senolytic agents in clearing senescent cells in vivo, and 3) determine the impact of senolytic agents on healthspan phenotypes. (PI: J. Kirkland) Funding Agency NIH/NIA Title Nathan Shock Aging Center Status Active Period 7/2015 - 6/2020 Role Principal Investigator Grant Detail   Funding Agency   Title Mechanisms by which CU/ZNSOD overexpression improves metabolic health in rats Status Active Period 9/2018 - 8/2019 Role Principal Investigator Grant Detail The goal of this project is to pursue our seminal findings by assessing the specific mechanisms that improve age-related changes in metabolic health under increased adiposity in rats with enhanced levels of a major antioxidant enzyme. We will investigate whether increasing an antioxidant enzyme in skeletal muscle and/or adipose tissue attenuates age-related changes in metabolic health by reducing senescent cell accumulation and enhancing insulin signaling. Funding Agency NIA Title Center for Testing Potential Anti-Aging Interventions Status Complete Period 8/2014 - 4/2019 Role Co-Investigator Grant Detail The goal of this project is to test pharmacological interventions for their anti-aging effects in a genetically heterogeneous stock of mice at 3 separate sites. This project is beginning its 3rd 5-year cycle of funding and has discovered several drugs that have life-extending properties as well as delay physiological aspects of aging. Funding Agency NIH Title The Mouse Phenotyping and Pathological Assessment Core (Cellular Senescence and Aging) Status Active Period 5/2012 - 4/2017 Role Co-Principal Investigator Grant Detail Core B - PI: Dr. Yuji Ikeno
  Project 1 - PI: Dr. Kirkland and Dr. Ikeno - CoPI

• Publications

  Abstract

  Roman MG, Flores LC, Cunningham GM, Zhang Y, Salmon A, Liu Y, Hubbard GB, Kirkland J, Pirtskhalava T, Tchkonia T, Ikeno Y. Mechanisms that extend lifespan in Sprague-Dawley rats overexpressing Cu/ZnSOD; 2015 Jan. (AGE). Cunningham GM, Roman MG, Flores LC, Zhang Y, Salmon A, Liu Y, Hubbard GB, Ikeno Y. Overexpression of thioredoxin in mitochondria combined with downregulation in the cytosol alters aging in mice; 2015 Jan. (AGE).

  Electronic/Web Publication

  Ikeno Y. New insights and current concepts of the oxidative stress theory of aging doi: 10.1016/j.abb; 2015 Jan. Zhu Y, Tchkonia T, Pirtskhalava T, Gower A, Ding H, Giorgadze N, Palmer AK, Ikeno Y, Borden G, Lenburg M, O'Hara SP, LaRusso NF, Miller JD, Roos CM, Verzosa GC, LeBrasseur NK, Wren JD, Farr JN, Khosla S, Stout MB, McGowan SJ, Fuhrmann-Stroissnigg H, Gurkar AU, Zhao J, Colangelo D, Dorronsoro A, Ling YY, Barghouthy AS, Navarro DC, Sano T, Robbins PD, Dorronsoro A, Ling YY, Barghouthy AS, Navarro DC, Sano T, Robbins PD, Niedernhofer LJ, Kirkland JL. The achilles' heel of sensecent cells: from transcriptome to senolytic drugs doi: 10.1111/acel.12344; 2015 Jan.

  Journal Article

  Mitchell, S.J., Bernier, M., Mattison, J.A., Aon, M.A., Kaiser, T.A., Anson, R.M., Ikeno, Y., Anderson, R.M., Ingram, D.K., and de Cabo, R. Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories Cell Metab 2019 Jan;29(1):221-228.e3.

  Ogrodnik, M., Zhu, Y., Langhi, L.G.P., Tchkonia, T., Kruger, P., Fielder, E., Vitorelli, S., Ruswhandi, R.A., Giorgadze, N., Pirtskhalava, T., Podgorni, O., Enikolopov, G., Johnson, K.O., Xu, M., Inman, C., Palmer, A.K., Schafer, M., Weigl, M., Ikeno, Y., Burns, T.C., Passos, J.F., von Zglinicki, T., Kirkland, J.L., and Jurk, D. Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis Cell Metab 2019 Jan;S1550(18):30745-9.

  Xu, M., Pirtskhalava, T., Farr, J.N., Weigand, B.M., Palmer, A.K., Weivoda, M.M., Inman, C.L., Ogrodnik, M.B., Hachfeld, C.M., Fraser, D.G., Onken, J.L., Johnson, K.O., Verzosa, G.C., Langhi, L.G.P., Weigl, M., Giorgadze, N., LeBrasseur, N.K., Miller, J.D., Jurk, D., Singh, R.J., Allison, D.B., Ejima, K., Hubbard, G.B., Ikeno, Y., Cubro, H., Garovic, V.D., Hou, X., Weroha, S.J., Robbins, P.D., Niedernhofer, L.J., Khosla, S., Tchkonia, T., and Kirkland, J.L. Senolytics improve physical function and increase lifespan in old age Nat Med 2018 Jan;24(8):1246-1256.

  Mao, K., Quipildor, G.F., Tabrizian, T., Novaj, A., Guan, F., Walters, R.O., Delahaye, F., Hubbard, G.B., Ikeno, Y., Ejima, K., Li, P., Allison, D.B., Salimi-Moosavi, H., Beltran, P.J., Cohen, P., Barzilai, N., and Huffman, D.M. Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice Nat Commun 2018 Jan;9(1).

  Flores, L.C., Roman, M.G., Cunningham, G.M., Cheng, C., Dube, S., Allen, C., Van Remmen, H., Hubbard, G.B., Saunders, T.L., and Ikeno, Y. Continuous overexpression of thioredoxin 1 enhances cancer development and does not extend maximum lifespan in male C57BL/6 mice Pathobiol Aging Age Relat Dis 2018 Jan;8(1). Habermehl, T.L., Parkinson, K.C., Hubbard, G.B., Ikeno, Y., Engelmeyer, L.I., Schumacher, B., and Mason, J.B. Extension of longevity and reduction of inflammation is ovarian-dependent, but germ cell-independent in post-reproductive female mice Geroscience 2018 Jan;.

  Cunningham, G.M., Flores, L.C., Roman, M.G., Cheng, C., Dube, S., Allen, C., Valentine, J.M., Hubbard, G.B., Bai, Y., Saunders, T.L., and Ikeno, Y. Thioredoxin overexpression in both the cytosol and mitochondria accelerates age-related disease and shortens lifespan in male C57BL/6 mice Geroscience 2018 Jan;40(5-6):453-468. Zhang, Y., Unnikrishnan, A., Deepa, S.S., Liu, Y., Li, Y., Ikeno, Y., Sosnowska, D., Van Remmen, H., and Richardson, A. A New Role for Oxidative Stress in Aging: The accelerated aging phenotype in Sod1-/- mice is correlated to increased cellular senescence Redox Biol 2017 Jan;11:30-37. 2.

  Ashpole, N.M., Logan, S., Yabluchanskiy, A., Mitschelen, M.C., Yan, H., Farley, J.A., Hodges, E.L., Ungvari, Z., Csiszar, A., Chen, S., Georgescu, C., Hubbard, G.B., Ikeno, Y., and Sonntag, W.E. IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan Geroscience 2017 Jan;39(2):129-145. Sataranatarajan K, Ikeno Y, Bokov A, Feliers D, Yalamanchili H, Lee HJ, Mariappan MM, Tabatabai-Mir H, Diaz V, Prasad S, Javors MA, Choudhury GG, Hubbard GB, Barnes JL, Richardson A, Kasinath BS. Rapamycin increases mortality in db/db mice, a mouse model of type-2 diabetes J Gerontol A Biol Sci Med Sci 2016 Jan;71:850-857.

  Ashpole NM, Herron JC, Mitschelen MC, Farley JA, Logan S, Yan H, Ungvari Z, Hodges EL, Csiszar A, Ikeno Y, Humphrey MB, Sonntag WE. IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms J Bone Miner Res 2015 Aug;.

  Ladiges W, Ikeno Y, Niedernhofer L, Mclndoe RA, Ciol M, Ritchey J, Liggitt D. The Geropathology Research Network. An interdisciplinary approach for integrating pathology into research on aging J Gerontol A Biol Sci Med Sci 2015 Aug;pii.

  Brandhorst S, Choi I, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Dubeau L, Yap LP, Park R, Vinciguerra M, Di Biase S, Mirzaei H, Mirisola MG, Childress P, Ji L, Groshen S, Penna F, Odetti P, Perin L, Conti PS, Ikeno Y, Kennedy BK, Cohen P, Morgan TE, Dorff TB, Longo VD. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance and healthspan Cell Metab 2015 Jul;22(1):86-99.

  List EO, Berryman DE, Ikeno Y, Hubbard GB, Funk K, Comisford R, Young JA, Stout MB, Tchkonia T, Masternak MM, Bartke A, Kirkland JL, Miller RA, Kopchick JJ. Removal of growth hormone receptor (GHR) in muscle of male mice replicates some of the health benefits seen in global GHR-/- mice Aging 2015 Jun;.

  Salmon AB, Lerner C, Ikeno Y, Motch Perrine SM, McCarter R, Sell C. Altered metabolism and resistance to obesity in long-lived mice producing reduced levels of IGF-I Am

  J Physiol Endocrinol Metab 2015 Apr;308(7):545-553. Cunningham GM, Roman MG, Flores LC, Zhang Y, Salmon A, Liu Y, Hubbard GB, Ikeno Y. The paradoxical role of thioredoxin on oxidative stress and aging Arch Biochem Biophys 2015 Jan;576:32-38.

  Liu Y, Qi W, Richardson A, Van Remmen H, Ikeno Y, Salmon AB. Oxidative damage associated with obesity is prevented by overexpression of CuZn- or Mn-superoxide dismutase Biochem Biophys Res Commun 2013 Jul;438(1):78-83.