Open AccessSpecific suppression of insulin sensitivity in growth hormone receptor gene‐disrupted ( GHR ‐ KO ) mice attenuates phenotypic features of slow aging
Author(s) -
Arum Oge,
Boparai Ravneet K.,
Saleh Jamal K.,
Wang Feiya,
Dirks Angela L.,
Turner Jeremy G.,
Kopchick John J.,
Liu JunLi,
Khardori Romesh K.,
Bartke Andrzej
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12262
Subject(s) - biology , growth hormone receptor , endocrinology , medicine , insulin , transgene , longevity , receptor , genetically modified mouse , senescence , knockout mouse , hormone , phenotype , gene , microbiology and biotechnology , growth hormone , genetics
Summary In addition to their extended lifespans, slow‐aging growth hormone receptor/binding protein gene‐disrupted (knockout) ( GHR ‐ KO ) mice are hypoinsulinemic and highly sensitive to the action of insulin. It has been proposed that this insulin sensitivity is important for their longevity and increased healthspan. We tested whether this insulin sensitivity of the GHR ‐ KO mouse is necessary for its retarded aging by abrogating that sensitivity with a transgenic alteration that improves development and secretory function of pancreatic β‐cells by expressing Igf‐1 under the rat insulin promoter 1 ( RIP :: IGF ‐1). The RIP :: IGF ‐1 transgene increased circulating insulin content in GHR ‐ KO mice, and thusly fully normalized their insulin sensitivity, without affecting the proliferation of any non‐β‐cell cell types. Multiple (nonsurvivorship) longevity‐associated physiological and endocrinological characteristics of these mice (namely beneficial blood glucose regulatory control, altered metabolism, and preservation of memory capabilities) were partially or completely normalized, thus supporting the causal role of insulin sensitivity for the decelerated senescence of GHR ‐ KO mice. We conclude that a delayed onset and/or decreased pace of aging can be hormonally regulated.