Specific suppression of insulin sensitivity in growth hormone receptor gene-disrupted (GHR-KO) mice attenuates phenotypic features of slow aging.
Aging Cell
; 13(6): 981-1000, 2014 Dec.
Article
en En
| MEDLINE
| ID: mdl-25244225
ABSTRACT
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 ß-cells by expressing Igf-1 under the rat insulin promoter 1 (RIPIGF-1). The RIPIGF-1 transgene increased circulating insulin content in GHR-KO mice, and thusly fully normalized their insulin sensitivity, without affecting the proliferation of any non-ß-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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de Somatotropina
/
Envejecimiento
/
Resistencia a la Insulina
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Factor I del Crecimiento Similar a la Insulina
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Insulina
/
Longevidad
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
Aging Cell
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos