Impact of aging and oxidative stress on specific components of excitation contraction coupling in regulating force generation.
Impact of aging and oxidative stress on specific components of excitation contraction coupling in regulating force generation.
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DOI：
10.1126/sciadv.add7377
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发表时间：
2022-10-28
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
与肌肉减少症相关的肌肉无力是老年人健康寿命和生活质量降低的主要原因。然而，衰老中肌肉无力的潜在机制尚未完全确定。我们研究了氧化应激和衰老对小鼠肌肉力量产生的特定分子机制的影响，以及缺乏抗氧化酶CuZnSod（Sod1KO）的小鼠和衰老（24个月大）野生型小鼠的皮肤透化单纤维。在两种模型中均发生肌肉力量丧失，可能是由于NKA信号传导和RyR稳定性改变导致的膜兴奋性降低、纤维Ca2+敏感性降低和通过修饰Cys674残基抑制SERCA活性、SR和胞质Ca2+稳态失调以及线粒体Ca2+缓冲和呼吸受损。我们的研究结果提供了一个更好的理解衰老和氧化应激对肌肉无力相关机制的具体影响，这可能指向未来对抗肌肉无力的干预措施。氧化修饰改变EC偶联的分子组分，导致衰老中的肌无力。
Muscle weakness associated with sarcopenia is a major contributor to reduced health span and quality of life in the elderly. However, the underlying mechanisms of muscle weakness in aging are not fully defined. We investigated the effect of oxidative stress and aging on specific molecular mechanisms involved in muscle force production in mice and skinned permeabilized single fibers in mice lacking the antioxidant enzyme CuZnSod (Sod1KO) and in aging (24-month-old) wild-type mice. Loss of muscle strength occurs in both models, potentially because of reduced membrane excitability with altered NKA signaling and RyR stability, decreased fiber Ca2+ sensitivity and suppressed SERCA activity via modification of the Cys674 residue, dysregulated SR and cytosolic Ca2+ homeostasis, and impaired mitochondrial Ca2+ buffering and respiration. Our results provide a better understanding of the specific impacts of aging and oxidative stress on mechanisms related to muscle weakness that may point to future interventions for countering muscle weakness. Oxidative modifications alter molecular components of EC coupling leading to muscle weakness in aging.
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影响因子：
7.8
作者：
Bhaskaran S;Pollock N;C Macpherson P;Ahn B;Piekarz KM;Staunton CA;Brown JL;Qaisar R;Vasilaki A;Richardson A;McArdle A;Jackson MJ;Brooks SV;Van Remmen H
通讯作者：
Van Remmen H
影响因子：
5.3
作者：
Lowe, DA;Husom, AD;Thompson, LV
通讯作者：
Thompson, LV
影响因子：
3.7
作者：
Bloemberg D;Quadrilatero J
通讯作者：
Quadrilatero J
影响因子：
4.8
作者：
Jang, Youngmok C.;Lustgarten, Michael S.;Van Remmen, Holly
通讯作者：
Van Remmen, Holly
影响因子：
4.6
作者：
Sodhi K;Nichols A;Mallick A;Klug RL;Liu J;Wang X;Srikanthan K;Goguet-Rubio P;Nawab A;Pratt R;Lilly MN;Sanabria JR;Xie Z;Abraham NG;Shapiro JI
通讯作者：
Shapiro JI