Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction
Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction
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DOI：
10.1152/ajpcell.00305.2012
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发表时间：
2013-04-01
影响因子：
5.5
通讯作者：
Parise, Gianni
中科院分区：
文献类型：
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作者：
McKay, Bryon R.;Ogborn, Daniel I.;Parise, Gianni
McKay BR、Ogborn DI、Baker JM、Toth KG、Tarnopolsky MA、Parise G。SOCS3 升高和 IL-6 信号传导改变与年龄相关的人类肌肉干细胞功能障碍有关。 Am J Physiol Cell Physiol 304：C717-C728，2013。首次发表于 2013 年 2 月 7 日； doi:10.1152/ajpcell.00305.2012.-衰老与循环白细胞介素 6 (IL-6) 增加和生肌能力降低有关，其特征是肌肉干细胞 [卫星细胞 (SC)] 活性降低。尽管 IL-6 对于正常 SC 功能很重要，但尚不清楚与衰老相关的 IL-6 升高是否会改变 SC 功能。我们假设，老年人中轻度长期升高的 IL-6 可能通过改变 IL-6 信号传导和升高的细胞因子信号传导 3 (SOCS3) 抑制物而与 SC 反应减弱相关。九名健康老年男性（OA；69.6 +/- 3.9 岁）和 9 名年轻男性对照（YC；21. 3 +/- 3.1 岁）完成了 4 组，每组 10 次重复单侧压腿和膝关节伸展（1-RM 的 75%）。在运动前以及运动后 3、24 和 48 小时获取肌肉活检和血液。 OA 中的基础 SC 数量比 YC 中低 33%，并且 OA 中的反应减弱。 IL-6(+)/Pax7(+)细胞在OA中表现出不同的反应，YC在3小时时增加至69%，并在24小时时达到峰值(72%)，而IL-6(+)/Pax7(+)细胞在OA中直到48小时才增加(61%)。 II 型纤维相关磷酸化信号转导器和转录激活剂 (pSTAT3)(+)/Pax7(+) 细胞在 OA 中表现出类似的延迟，直到 48 小时才增加（相对于 YC 中的 3 小时）。 OA 中的 SOCS3 蛋白含量高出 86%。这些数据表明，正常 SC 功能存在与年龄相关的损伤，这似乎受到 OA SC 中 SOCS3 蛋白和 IL-6 和 pSTAT3 延迟诱导的影响。总的来说，这些数据表明，衰老导致的 IL-6 信号失调导致肌肉干细胞反应迟钝。
McKay BR, Ogborn DI, Baker JM, Toth KG, Tarnopolsky MA, Parise G. Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction. Am J Physiol Cell Physiol 304: C717-C728, 2013. First published February 7, 2013; doi:10.1152/ajpcell.00305.2012.-Aging is associated with increased circulating interleukin-6 (IL-6) and a reduced myogenic capacity, marked by reduced muscle stem cell [ satellite cell (SC)] activity. Although IL-6 is important for normal SC function, it is unclear whether elevated IL-6 associated with aging alters SC function. We hypothesized that mild chronically elevated IL-6 would be associated with a blunted SC response through altered IL-6 signaling and elevated suppressor of cytokine signaling-3 (SOCS3) in the elderly. Nine healthy older adult men (OA; 69.6 +/- 3.9 yr) and 9 young male controls (YC; 21. 3 +/- 3.1 yr) completed 4 sets of 10 repetitions of unilateral leg press and knee extension (75% of 1-RM). Muscle biopsies and blood were obtained before and 3, 24, and 48 h after exercise. Basal SC number was 33% lower in OA vs. YC, and the response was blunted in OA. IL-6(+)/Pax7(+) cells demonstrated a divergent response in OA, with YC increasing to 69% at 3 h and peaking at 24 h (72%), while IL-6(+)/Pax7(+) cells were not increased until 48 h in OA (61%). Type II fiber-associated phosphorylated signal transducer and activator of transcription (pSTAT3)(+)/Pax7(+) cells demonstrated a similar delay in OA, not increasing until 48 h (vs. 3 h in YC). SOCS3 protein was 86% higher in OA. These data demonstrate an age-related impairment in normal SC function that appears to be influenced by SOCS3 protein and delayed induction of IL-6 and pSTAT3 in the SCs of OA. Collectively, these data suggest dysregulated IL-6 signaling as a consequence of aging contributes to the blunted muscle stem cell response.