A Novel Stable Isotope Approach Demonstrates Surprising Degree of Age-Related Decline in Skeletal Muscle Collagen Proteostasis.
A Novel Stable Isotope Approach Demonstrates Surprising Degree of Age-Related Decline in Skeletal Muscle Collagen Proteostasis.
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DOI：
10.1093/function/zqab028
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Miller BF
中科院分区：
文献类型：
--
作者：
Abbott CB;Lawrence MM;Kobak KA;Lopes EBP;Peelor FF 3rd;Donald EJ;Van Remmen H;Griffin TM;Miller BF
胶原蛋白的周转中的胶原蛋白相关恶化加速细胞外基质纤维化并阻碍对外部刺激的适应。这个项目试图通过研究我们所说的动态蛋白库来了解随着年龄增长骨骼肌纤维化的因素。我们假设，肌肉胶原蛋白的动态蛋白池大小随年龄的增长而减少，从而表明蛋白质稳态维持（即，维持蛋白质稳态的能力）的减少，并且未能解释这些变化会影响示踪剂测量的合成率的解释。我们在成年（6个月）和老年（23个月）小鼠中使用氧化氘（D2O）标记长达60天。成人骨骼肌中的动态蛋白质库在胫骨前肌（TA）中为65%，但在腓肠肌（Gastroc）中仅为28%。在老年肌肉中，动态蛋白池进一步下降到只有35%和14%，分别为TA和Gastroc。我们发现，这种动态池大小的损失与纤维化标志物的增加和蛋白质稳定维持的减少有关。我们证明，老年肌肉具有较高的胶原蛋白合成率和较低的胶原蛋白分解率，这导致胶原蛋白积累。我们进一步证明了蛋白质完全更新的正常假设和同位素标记单个样本的标准实践对解释纤维化的发生具有深远的影响。随着年龄的增长，保持肌肉功能的策略应该集中在动态蛋白质库上，并注意评估这些变化的方法策略。
Age-related deterioration in turnover of collagen proteins accelerates extracellular matrix fibrosis and hinders adaptation to external stimuli. This project sought to understand factors that increase skeletal muscle fibrosis with age by studying what we term the dynamic protein pool. We hypothesized that the dynamic protein pool size of muscle collagen decreases with age, thus indicating a decrease in proteostatic maintenance (ie, ability to maintain proteostasis), and that failure to account for these changes impacts the interpretation of tracer-measured synthesis rates. We used deuterium oxide (D2O) labeling for up to 60 days in adult (6 months) and old (23 months) mice. The dynamic protein pool in adult skeletal muscle was 65% in tibialis anterior (TA), but only 28% in gastrocnemius (Gastroc). In aged muscle, the dynamic protein pool was further decreased to only 35% and 14% for TA and Gastroc, respectively. We showed that this loss in dynamic pool size was associated with increases in markers of fibrosis and decreased proteostatic maintenance. We demonstrate that aged muscle has higher rates of collagen protein synthesis and lower rates of collagen protein breakdown, which causes collagen accumulation. We further demonstrated that the normal assumption of complete protein renewal and the standard practice of taking a single sample with isotope labeling have profound impacts on interpretation of the genesis of fibrosis. Strategies to maintain muscle function with aging should focus on the dynamic protein pool with attention to methodological strategies to assess those changes.
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影响因子：
5.6
作者：
Lawrence, Marcus M.;Van Pelt, Douglas W.;Dupont-Versteegden, Esther E.
通讯作者：
Dupont-Versteegden, Esther E.
DOI：
10.1152/ajpendo.00300.2005
发表时间：
2006-01-01
影响因子：
5.1
作者：
Miller, BF;Hansen, M;Kjaer, M
通讯作者：
Kjaer, M
影响因子：
2.8
作者：
GOLDSPINK, G;FERNANDES, K;WELLS, DJ
通讯作者：
WELLS, DJ
DOI：
10.1096/fj.12-225599
发表时间：
2013-05
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Heinemeier KM;Schjerling P;Heinemeier J;Magnusson SP;Kjaer M
通讯作者：
Kjaer M
影响因子：
8.3
作者：
Fleenor, Bradley S.;Ouyang, An;Emter, Craig A.
通讯作者：
Emter, Craig A.