title: WNT signaling suppression in the senescent human thymus.
abstract: Human thymus is completely developed in late fetal stages and its function peaks in newborns. After the first year of life, the thymus undergoes a progressive atrophy that dramatically decreases de novo T-lymphocyte maturation. Hormonal signaling and changes in the microRNA expression network are identified as underlying causes of human thymus involution. However, specific pathways involved in the age-related loss of thymic function remain unknown. In this study, we analyzed differential gene-expression profile and microRNA expression in elderly (70 years old) and young (less than 10 months old and 11 years old) human thymic samples. Our data have shown that WNT pathway deregulation through the overexpression of different inhibitors by the nonadipocytic component of the human thymus stimulates the age-related involution. These results are of particular interest because interference of WNT signaling has been demonstrated in both animal models and in vitro studies, with the three major hallmarks of thymic involution: (i) epithelial structure disruption, (ii) adipogenic process, and (iii) thymocyte development arrest. Thus, our results suggest that secreted inhibitors of the WNT pathway could be explored as a novel therapeutical target in the reversal of the age-related thymic involution.
authors.affiliation: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain. Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine. Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain. s.ferrandomartinez@gmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrando-Martínez
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine. Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Ruiz-Mateos
authors.affiliation: Department of Immunology and Medicine, Sloan Kettering Institute, New York City, USA.
authors.forename: Jarrod A
authors.initials: JA
authors.lastname: Dudakov
authors.affiliation: Department of Immunology and Medicine, Sloan Kettering Institute, New York City, USA.
authors.forename: Enrico
authors.initials: E
authors.lastname: Velardi
authors.affiliation: Department of Biotechnology, VIBT-BOKU, University of Natural Resources and Applied Life Sciences, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Grillari
authors.affiliation: Chair of Bioinformatics, BOKU University Vienna, Austria and Life Sciences, University of Warwick, UK.
authors.forename: David P
authors.initials: DP
authors.lastname: Kreil
authors.affiliation: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernandez
authors.affiliation: Department of Immunology and Medicine, Sloan Kettering Institute, New York City, USA.
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine. Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
mesh_terms: D017667:Adipocytes / Q000502:physiology; D000368:Aged; D000375:Aging / Q000473:pathology / Q000502:physiology*; D001284:Atrophy / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D046228:Microarray Analysis; D008875:Middle Aged; D013950:Thymus Gland / Q000473:pathology*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D035683:MicroRNAs
keywords: Aging.; Human thymus; Thymus involution; WNT pathway