Diverse effects of somatopause and aging on the skeleton

文摘:

ABSTRACT: Our project focuses on the modulation of bone quality during aging, which we hypothesize is controlled by osteocytes. Our studies are designed to determine the interactions between `intact aging' and somatopause in the aging skeleton and to identify the cellular mechanisms involved. Cellular and molecular analyses are aimed at linking osteocyte connectivity, mitochondrial function and metabolism to bone tissue composition. These studies capitalize on using a unique mouse model of age-induced somatopause, which is based on the use of tamoxifen-inducible (i) ubiquitously-expressed Cre in conjunction with the GHR floxed gene (iGHRKO), a previously validated model (PMID:27732088). Studies accomplished so far have revealed that somatopause in the iGHRKO impairs bone morphology, bone tissue quality, osteocyte connectivity, and osteocyte mitochondrial function. An administrative supplement is requested for complementary studies as part of all aims of the parent grant. The overall goal is to test how interventions that are known to modify the GH/IGF axis and have beneficial effect on lifespan will affect the aging skeleton.