Title

The Negative Effect Of Prolonged Somatotrophic/Insulin Signaling On An Adult Bone Marrow-Residing Population Of Pluripotent Very Small Embryonic-Like Stem Cells (Vsels)

Keywords

Aging; GH; IGF-1; VSELs

Abstract

It is well known that attenuated insulin/insulin-like growth factor signaling (IIS) has a positive effect on longevity in several animal species, including mice. Here, we demonstrate that a population of murine pluripotent very small embryonic-like stem cells (VSELs) that reside in bone marrow (BM) is protected from premature depletion during aging by intrinsic parental gene imprinting mechanisms and the level of circulating insulin-like growth factor-I (IGF-I). Accordingly, an increase in the circulating level of IGF-I, as seen in short-lived bovine growth hormone (bGH)-expressing transgenic mice, which age prematurely, as well as in wild-type animals injected for 2 months with bGH, leads to accelerated depletion of VSELs from bone marrow (BM). In contrast, long-living GHR-null or Ames dwarf mice, which have very low levels of circulating IGF-I, exhibit a significantly higher number of VSELs in BM than their littermates at the same age. However, the number of VSELs in these animals decreases after GH or IGF-I treatment. These changes in the level of plasma-circulating IGF-I corroborate with changes in the genomic imprinting status of crucial genes involved in IIS, such as Igf-2-H19, RasGRF1, and Ig2R. Thus, we propose that a chronic increase in IIS contributes to aging by premature depletion of pluripotent VSELs in adult tissues. © 2011 American Aging Association.

Publication Date

4-1-2013

Publication Title

Age

Volume

35

Issue

2

Number of Pages

315-330

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1007/s11357-011-9364-8

Socpus ID

84880573002 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84880573002

This document is currently not available here.

Share

COinS