Serum and muscle interleukin-15 levels decrease in aging mice: correlation with declines in soluble interleukin-15 receptor alpha expression.

Serum and muscle interleukin-15 levels decrease in aging mice: correlation with declines in soluble interleukin-15 receptor alpha expression.
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DOI:
10.1016/j.exger.2009.10.012
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发表时间:
2010-02
影响因子:
3.9
通讯作者:
Wolden-Hanson, Tami
Wolden-Hanson, Tami
中科院分区:
医学2区
文献类型:
--
作者:
Quinn, LeBris S.;Anderson, Barbara G.;Strait-Bodey, Lena;Wolden-Hanson, Tami

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白介素15(IL-15)是一种骨骼肌源性细胞因子,对肌肉质量和身体成分有良好的影响。调节IL-15水平被认为是治疗骨质疏松症和与年龄相关的肥胖症的一种方法。然而,目前尚不清楚IL-15水平在衰老过程中是否会发生变化,因为在小鼠体内测量生理浓度的IL-15在技术上一直很困难,而且IL-15的翻译调节也很复杂。此外,IL-15受体α(IL-15Rα)可以是膜相关受体复合体的一部分,也可以是一种稳定IL-15、促进IL-15分泌的可溶性形式。在这里,我们报告了对小鼠IL-15生理水平的测量,并确定肌肉和血清IL-15水平随着年龄的增长而逐渐下降。然而,IL-15mRNA和IL-15受体的膜相关亚单位在肌肉中的表达不随年龄变化。SIL-15Rα(sIL-15Rα)表达随增龄下降5倍,血清IL-15水平与肌肉sIL-15mRNA表达水平高度相关,提示sIL-15Rα表达下降导致循环IL-15水平在增龄过程中下降。这些发现补充了描述人类IL-15Rα基因中影响肌肉和肥胖的几个单核苷酸多态性的研究,并为进一步研究IL-15和sIL-15Rα作为人类模型在确定衰老小鼠体成分方面提供了技术基础。
Interleukin-15 (IL-15) is a skeletal muscle-derived cytokine with favorable effects on muscle mass and body composition. Modulation of IL-15 levels has been suggested as a treatment for sarcopenia and age-associated increases in adiposity. However, it is unclear whether IL-15 levels change during aging, as measurement of IL-15 at physiological concentrations in mice has been technically difficult, and translational regulation of IL-15 is complex. Moreover, the IL-15 receptor alpha (IL-15Rα) can comprise part of a membrane-associated receptor complex, or appear as a soluble form which stabilizes IL-15 and facilitates IL-15 secretion. Here, we report measurement of physiological levels of murine IL-15, and determine that muscle and serum IL-15 levels decline progressively with age. However, expression of IL-15 mRNA and membrane-associated subunits of the IL-15 receptor did not change with age in muscle. Expression of soluble IL-15Rα (sIL-15Rα) mRNA declined 5-fold with age, and serum IL-15 levels correlated highly with muscle sIL-15 mRNA expression, suggesting declines in sIL-15Rα expression lead to decreased circulating IL-15 levels during aging. These findings complement studies which described several single-nucleotide polymorphisms in the human IL-15Rα gene which impact muscularity and adiposity, and provide a technical basis for further investigation of IL-15 and the sIL-15Rα in determining body composition in aging mice, as a model for humans.
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发表时间: 2007-04-01
影响因子: 5.5
作者:
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期刊: SCIENCE
影响因子: 56.9
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