title: Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a.
abstract: Involution of the thymus results in reduced production of naive T cells, and this in turn is thought to contribute to impaired immunity in the elderly. Early T-cell progenitors (ETPs), the most immature intrathymic T-cell precursors, harvested from the involuted thymus exhibit a diminished proliferative potential and increased rate of apoptosis and as a result their number is significantly reduced. In the present study, we show that these age-induced alterations result in part from increased expression of the Ink4a tumor-suppressor gene in ETPs. We also show that repression of Ink4a in aged ETPs results in their partial rejuvenation and that this can be accomplished by in vivo fibroblast growth factor 7 administration. These results define a genetic basis for thymocyte progenitor aging and demonstrate that the senescence-associated gene Ink4a can be pharmacologically repressed in ETPs to partially reverse the effects of aging.
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Berent-Maoz
authors.forename: Encarnacion
authors.initials: E
authors.lastname: Montecino-Rodriguez
authors.forename: Robert A J
authors.initials: RA
authors.lastname: Signer
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dorshkind
mesh_terms: D000375:Aging / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D016922:Cellular Senescence / Q000187:drug effects* / Q000276:immunology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; C496453:FGF7 protein, human; D051523:Fibroblast Growth Factor 7