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Lifespan of long-lived growth hormone receptor knockout mice was not normalized by housing at 30°C since weaning.
Aging Cell ( IF 7.8 ) Pub Date : 2020-02-28 , DOI: 10.1111/acel.13123
Yimin Fang 1 , Samuel McFadden 1 , Justin Darcy 2 , Erin R Hascup 1, 3 , Kevin N Hascup 1, 3, 4 , Andrzej Bartke 2
Affiliation  

Growth hormone receptor knockout (GHRKO) mice are remarkably long‐lived and have improved glucose homeostasis along with altered energy metabolism which manifests through decreased respiratory quotient (RQ) and increased oxygen consumption (VO2). Short‐term exposure of these animals to increased environmental temperature (eT) at 30°C can normalize their VO2 and RQ. We hypothesized that increased heat loss in the diminutive GHRKO mice housed at 23°C and the consequent metabolic adjustments to meet the increased energy demand for thermogenesis may promote extension of longevity, and preventing these adjustments by chronic exposure to increased eT will reduce or eliminate their longevity advantage. To test these hypotheses, GHRKO mice were housed at increased eT (30°C) since weaning. Here, we report that contrasting with the effects of short‐term exposure of adult GHRKO mice to 30°C, transferring juvenile GHRKO mice to chronic housing at 30°C did not normalize the examined parameters of energy metabolism and glucose homeostasis. Moreover, despite decreased expression levels of thermogenic genes in brown adipose tissue (BAT) and elevated core body temperature, the lifespan of male GHRKO mice was not reduced, while the lifespan of female GHRKO mice was increased, along with improved glucose homeostasis. The results indicate that GHRKO mice have intrinsic features that help maintain their delayed, healthy aging, and extended longevity at both 23°C and 30°C.

中文翻译:

自断奶以来,长期处于30°C的恒温环境无法使长寿的生长激素受体敲除小鼠的寿命正常化。

敲除生长激素受体(GHRKO)的小鼠寿命长,并具有改善的葡萄糖稳态以及改变的能量代谢,这通过降低呼吸商(RQ)和增加氧气消耗(VO 2)来体现。将这些动物短期暴露于30°C的升高的环境温度(eT)中,可使它们的VO 2正常化和RQ。我们假设,在23°C时饲养的矮小的GHRKO小鼠的热量损失增加,以及随之而来的代谢调整以满足生热的能量需求增加,可能会延长寿命,而通过长期暴露于eT升高来防止这些调整会减少或消除它们的寿命。长寿的优势。为了检验这些假设,自断奶以来将GHRKO小鼠饲养在升高的eT(30°C)下。在这里,我们报道与成年GHRKO小鼠短期暴露于30°C的影响相反,将少年GHRKO小鼠转移至30°C的慢性住房并没有使能量代谢和葡萄糖稳态的检查参数正常化。此外,尽管棕色脂肪组织(BAT)中的致热基因表达水平下降,核心体温升高,雄性GHRKO小鼠的寿命没有减少,雌性GHRKO小鼠的寿命增加了,并且葡萄糖稳态得到了改善。结果表明,GHRKO小鼠具有固有的功能,有助于在23°C和30°C下保持其延迟的健康衰老和延长寿命。
更新日期:2020-02-28
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