Comparative gene expression and phenotype analyses of skeletal muscle from aged wild-type and PAPP-A-deficient mice.
Comparative gene expression and phenotype analyses of skeletal muscle from aged wild-type and PAPP-A-deficient mice.
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DOI：
10.1016/j.exger.2016.04.005
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发表时间：
2016-07
影响因子：
3.9
通讯作者：
Nair KS
中科院分区：
文献类型：
--
作者：
Conover CA;Bale LK;Nair KS
妊娠相关血浆蛋白-A（PAPP-A）缺陷的小鼠具有延长的寿命，这与老年退行性疾病（如心肌病和肾病）的发病率和严重程度降低有关。本研究探讨了PAPP-A缺乏对骨骼肌衰老的影响。对来自相同性别和来自同一窝（"子宫伴侣"）的18个月大野生型（WT）和PAPP-A敲除（KO）小鼠的比目鱼肌进行全基因组表达谱分析，以鉴定骨骼肌老化及其在PAPP-A缺乏症中延迟的潜在机制。与WT肌肉相比，PAPP-A KO中调节的顶级基因与增加的肌肉功能、增加的代谢（特别是脂质代谢）和减少的应激相关。在来自PAPP-A KO小鼠的solei中，纤维横截面积显著增加。体外收缩性实验表明PAPP-A KO小鼠的鞋底比力增加，疲劳减少。与WT小鼠相比，老年PAPP-A KO小鼠骨骼肌的固有线粒体氧化能力显著增加。此外，18个月大的PAPP-A KO小鼠在跑步机上跑步的耐力显著增强。因此，小鼠中PAPP-A缺乏与健康骨骼肌功能随年龄增长的指数相关。
Mice deficient in pregnancy-associated plasma protein-A (PAPP-A) have extended lifespan associated with decreased incidence and severity of degenerative diseases of age, such as cardiomyopathy and nephropathy. In this study, the effect of PAPP-A deficiency on aging skeletal muscle was investigated. Whole-genome expression profiling was performed on soleus muscles from 18-month-old wild-type (WT) and PAPP-A knock-out (KO) mice of the same sex and from the same litter (‘womb-mates’) to identify potential mechanisms of skeletal muscle aging and its retardation in PAPP-A deficiency. Top genes regulated in PAPP-A KO compared to WT muscle were associated with increased muscle function, increased metabolism, in particular lipid metabolism, and decreased stress. Fiber cross-sectional area was significantly increased in solei from PAPP-A KO mice. In vitro contractility experiments indicated increased specific force and decreased fatigue in solei from PAPP-A KO mice. Intrinsic mitochondrial oxidative capacity was significantly increased in skeletal muscle of aged PAPP-A KO compared to WT mice. Moreover, 18-month-old PAPP-A KO mice exhibited significantly enhanced endurance running on a treadmill. Thus, PAPP-A deficiency in mice is associated with indices of healthy skeletal muscle function with age.