Institute of Sport, Exercise and Active Living, Muscle, Ions and Exercise Group, Victoria University, Melbourne, VIC 8001, Australia.
J Appl Physiol (1985). 2012 Nov;113(10):1505-11. doi: 10.1152/japplphysiol.01032.2011. Epub 2012 Aug 30.
Aging is associated with reduced muscle mass, weakness, and increased fatigability. In skeletal muscle, the Na(+)-K(+) pump (NKA) is important in regulating Na(+)-K(+) gradients, membrane excitability, and thus contractility, but the effects of aging on muscle NKA are unclear. We investigated whether aging is linked with reduced muscle NKA by contrasting muscle NKA isoform gene expression and protein abundance, and NKA total content in 17 Elderly (66.8 ± 6.4 yr, mean ± SD) and 16 Young adults (23.9 ± 2.2 yr). Participants underwent peak oxygen consumption assessment and a vastus lateralis muscle biopsy, which was analyzed for NKA α(1)-, α(2)-, α(3)-, β(1)-, β(2)-, and β(3)-isoform gene expression (real-time RT-PCR), protein abundance (immunoblotting), and NKA total content ([(3)H]ouabain binding sites). The Elderly had lower peak oxygen consumption (-36.7%, P = 0.000), strength (-36.3%, P = 0.001), NKA α(2)- (-24.4%, 11.9 ± 4.4 vs. 9.0 ± 2.7 arbitrary units, P = 0.049), and NKA β(3)-protein abundance (-23.0%, P = 0.041) than Young. The β(3)-mRNA was higher in Elderly compared with Young (P = 0.011). No differences were observed between groups for other NKA isoform mRNA or protein abundance, or for [(3)H]ouabain binding site content. Thus skeletal muscle in elderly individuals was characterized by decreased NKA α(2)- and β(3)-protein abundance, but unchanged α(1) abundance and [(3)H]ouabain binding. The latter was likely caused by reduced α(2) abundance with aging, preventing an otherwise higher [(3)H]ouabain binding that might occur with a greater membrane density in smaller muscle fibers. Further study is required to verify reduced muscle NKA α(2) with aging and possible contributions to impaired exercise capability and daily living activities.
衰老是与肌肉质量减少、肌肉无力和疲劳增加有关。在骨骼肌中，Na(+)-K(+)泵（NKA）对于调节 Na(+)-K(+)梯度、膜兴奋性以及因此的收缩性非常重要，但是衰老对肌肉 NKA 的影响尚不清楚。我们通过对比 17 名老年人（66.8 ± 6.4 岁，平均值 ± 标准差）和 16 名年轻人（23.9 ± 2.2 岁）的肌肉 NKA 同工型基因表达和蛋白丰度以及 NKA 总量，研究了衰老与肌肉 NKA 减少之间的关系。参与者进行了峰值耗氧量评估和股外侧肌活检，并用 [(3)H]哇巴因结合位点对 NKA α(1)-、α(2)-、α(3)-、β(1)-、β(2)-和 β(3)-同工型基因表达（实时 RT-PCR）、蛋白丰度（免疫印迹）和 NKA 总量进行了分析。老年人的峰值耗氧量较低（-36.7%，P = 0.000）、力量较低（-36.3%，P = 0.001）、NKA α(2)-较低（-24.4%，11.9 ± 4.4 比 9.0 ± 2.7 任意单位，P = 0.049）、NKA β(3)-蛋白丰度较低（-23.0%，P = 0.041）。与年轻人相比，老年人的 β(3)-mRNA 更高（P = 0.011）。两组之间其他 NKA 同工型 mRNA 或蛋白丰度或 [(3)H]哇巴因结合位点含量没有差异。因此，老年人的骨骼肌表现为 NKA α(2)-和 β(3)-蛋白丰度降低，但 α(1)丰度和 [(3)H]哇巴因结合不变。后者可能是由于衰老导致 NKA α(2)减少，从而防止了由于较小肌肉纤维中膜密度增加而可能发生的更高 [(3)H]哇巴因结合。需要进一步的研究来验证衰老时肌肉 NKA α(2)减少以及对运动能力和日常活动能力受损的可能贡献。
