Evidence that hematopoietic stem cell function is preserved during aging in long-lived S6K1 mutant mice

Selman, C. , Sinclair, A., Pedroni, S. M.A., Irvine, E. E., Michie, A. M. and Withers, D. J. (2016) Evidence that hematopoietic stem cell function is preserved during aging in long-lived S6K1 mutant mice. Oncotarget, 7, 21. (doi: 10.18632/oncotarget.8729) (PMID:27083004)

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Abstract

The mechanistic target of rapamycin (mTOR) signalling pathway plays a highly conserved role in aging; mice lacking ribosomal protein S6 kinase 1 (S6K1-/-) have extended lifespan and healthspan relative to wild type (WT) controls. Exactly how reduced mTOR signalling induces such effects is unclear, although preservation of stem cell function may be important. We show, using gene expression analyses, that there was a reduction in expression of cell cycle genes in young (12 week) and aged (80 week) S6K1-/- BM-derived c-Kit+ cells when compared to age-matched WT mice, suggesting that these cells are more quiescent in S6K1-/- mice. In addition, we investigated hematopoietic stem cell (HSC) frequency and function in young and aged S6K1-/- and WT mice. Young, but not aged, S6K1-/- mice had more LSK (lineage-, c-Kit+, Sca-1+) cells (% of bone marrow (BM)), including the most primitive long-term repopulating HSC (LT-HSC) relative to WT controls. Donor-derived engraftment of LT-HSCs in recipient mice was unaffected by genotype in young mice, but was enhanced in transplants using LT-HSCs derived from aged S6K1-/- mice. Our results are the first to provide evidence that age-associated HSC functional decline is ameliorated in a long-lived mTOR mutant mouse.

Item Type:Articles
Additional Information:This work was supported through start-up funds from the University of Glasgow (College of Medical, Veterinary and Life Sciences) to CS and a Wellcome Trust Strategic Award (reference 098565/Z/12/Z) to DJW.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Selman, Professor Colin and Michie, Dr Alison and Sinclair, Miss Amy
Authors: Selman, C., Sinclair, A., Pedroni, S. M.A., Irvine, E. E., Michie, A. M., and Withers, D. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncotarget
Publisher:Impact Journals
ISSN:1949-2553
ISSN (Online):1949-2553
Published Online:13 April 2016
Copyright Holders:Copyright © 2016 Impact Journals
First Published:First published in Oncotarget
Publisher Policy:Reproduced under a Creative Commons License

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