The negative effect of prolonged somatotrophic/insulin signaling on an adult bone marrow-residing population of pluripotent very small embryonic-like stem cells (VSELs)

    Authors

    M. Kucia; M. Masternak; R. Liu; D. M. Shin; J. Ratajczak; K. Mierzejewska; A. Spong; J. J. Kopchick; A. Bartke;M. Z. Ratajczak

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    Abbreviated Journal Title

    Age

    Keywords

    VSELs; IGF-1; GH; Aging; GROWTH-FACTOR-I; LIFE-SPAN; HEMATOPOIETIC STEM; DWARF MICE; ENDOCRINE; REGULATION; TARGETED DISRUPTION; TRANSGENIC MICE; INSULIN; PROTEIN; RECEPTOR; Geriatrics & Gerontology

    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.

    Journal Title

    Age

    Volume

    35

    Issue/Number

    2

    Publication Date

    1-1-2013

    Document Type

    Article

    Language

    English

    First Page

    315

    Last Page

    330

    WOS Identifier

    WOS:000316065200005

    ISSN

    0161-9152

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