Format

Send to

Choose Destination
See comment in PubMed Commons below
Blood. 2012 Jun 14;119(24):5715-21. doi: 10.1182/blood-2011-12-400002. Epub 2012 May 3.

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

Author information

1
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA.

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.

PMID:
22555975
PMCID:
PMC3382931
DOI:
10.1182/blood-2011-12-400002
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center