Work

Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a

Year: 2012

Type: article

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.

Source: Blood

DOI: 10.1182/blood-2011-12-400002

Authors: Beata Berent-Maoz, Encarnacion Montecino-Rodriguez, Robert A. J. Signer, Kenneth Dorshkind

Institution: University of California, Los Angeles

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of Allergy and Infectious Diseases