Activity-dependent signaling in aging skeletal muscle
衰老骨骼肌中的活动依赖性信号传导
基本信息
- 批准号:7111735
- 负责人:
- 金额:$ 7.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-09-01 至 2008-08-31
- 项目状态:已结题
- 来源:
- 关键词:agingbinding sitesbiological signal transductionelectrostimulusenzyme activityexercisegenetic translationlaboratory ratmessenger RNAmuscle contractionmuscle hypertrophymuscle proteinsphosphatidylinositol 3 kinasephosphorylationposttranscriptional RNA processingprotein biosynthesisribosomal proteinssarcopeniaserine threonine protein kinasestriated muscles
项目摘要
DESCRIPTION (provided by applicant): The age-related loss of skeletal muscle mass is associated with well-characterized functional limitations and physical disability. Although resistance training attenuates age-related muscle loss, the cellular processes that initiate muscle hypertrophy and the extent to which they are preserved with age are not well understood. The 70-kDa S6 protein kinase (p70S6K) is a downstream target of the protein kinase B/mammalian target of rapamycin (Akt/mTOR) pathway that has been implicated in the regulation of muscle size during overload and disuse atrophy. This and other kinases of the Akt/mTOR pathway affect protein translation by regulating translational inhibitors such as glycogen synthase kinase 3 (GSK-3), phosphorylating key ribosomal proteins, and influencing the availability of eukaryotic initiation factors (elF's). We propose to test the hypotheses that 1) aging is associated with a reduced activation of the Akt/mTOR pathway 2) the reduced phosphorylation of p70S6K and mTOR results in a decreased number of elF4E-elF4G complexes and a reduction in muscle protein synthesis, and 3) chronic contractile activity results in blunted muscle hypertrophy in older animals due to a reduced activation of the Akt/mTOR pathway. We propose to use electrical stimulation to simulate acute resistance exercise in young and old rat hindlimbs, and surgical ablation of synergistic muscles to model the effects of chronic contractile activity. Specifically, we will 1) characterize Akt/mTOR signaling after a single bout of resistance exercise at young age, 2) assess the effects of resistance exercise on the number of capped mRNA binding sites (elF4E-elF4G) available for protein translation at young age, 3) compare the activation of Akt/mTOR, formation of elF4E-elF4G complexes, and protein synthesis of young, middle aged, and old rats in response to acute contractile activity, 4) compare the activation of Akt/mTOR, formation of elF4E-elF4G, and protein synthesis of young, middle aged, and old rats in response to chronic ablation of synergistic muscles. Muscle samples at several time points will be analyzed for p70S6K, Akt, mTOR, 4EBP1, and GSK-3 phosphorylation, elF4E-elF4G complexes, and skeletal muscle protein synthesis. We believe that the identification of molecular dysregulation in the Akt/mTOR pathway associated with age-related muscle atrophy will establish the groundwork for studies aimed at correcting these deficiencies and improving the efficacy of resistance training and other therapeutic interventions in the elderly.
描述(由申请人提供):与年龄相关的骨骼肌质量丧失与特征良好的功能局限性和身体残疾有关。尽管抗药性训练减弱了与年龄相关的肌肉损失,但启动肌肉肥大的细胞过程以及随着年龄的增长的保留程度。 70-KDA S6蛋白激酶(P70S6K)是蛋白激酶B/哺乳动物雷帕霉素(AKT/MTOR)途径的下游靶标,该靶标与过载和失去萎缩期间的肌肉大小相关。 AKT/MTOR途径的这种激酶和其他激酶通过调节转化抑制剂(例如糖原合酶激酶3(GSK-3),磷酸化的键核糖体蛋白质以及影响真实性化启动因子(ELF)的可用性来影响蛋白质的翻译。我们提出测试假设,即1)衰老与Akt/mTOR途径的激活减少有关2)p70S6K和MTOR的磷酸化降低导致ELF4E-FELF4G复合物的数量减少,并减少了肌肉蛋白质的降低,以及肌肉蛋白质的降低,以及在乳腺癌中降低的慢性动物,慢性合同性的动作量降低了慢性的慢性肌肉激活的慢性肌肉激活,使其慢性化的动物激活量化。 Akt/mtor途径。我们建议使用电刺激来模拟年轻大鼠和老鼠后肢的急性抗性运动,以及对协同肌肉的手术消融来模拟慢性收缩活性的影响。具体而言,我们将1)在年轻时进行一次抵抗运动后的AKT/MTOR信号传导,2)评估抵抗运动对可用于蛋白质翻译的限制mRNA结合位点(ELF4E-FELF4G)的影响,年轻时可用于蛋白质,3)比较了AKT/MTOR的激活,与AKT/MTOR的成立,较小的Elf4e-Elf4e-efforment,以及Elf4e-efforment,以及Elf4e-4G的复杂性,以及Elf4G的复杂性,以及Elf4g的综合体,大鼠响应急性收缩活性,4)比较Akt/mTOR的激活,ELF4E-FELP4G的形成以及年轻,中年和老鼠的蛋白质合成,以响应协同肌肉的慢性消融。 P70S6K,AKT,MTOR,4EBP1和GSK-3磷酸化,ELF4E-FELF4G复合物和骨骼肌蛋白蛋白合成的肌肉样本将在几个时间点进行分析。我们认为,与年龄相关的肌肉萎缩相关的AKT/MTOR途径中分子失调的鉴定将为旨在纠正这些缺陷并提高耐药性训练和其他治疗性干预措施的疗效的研究建立基础。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Roger A. Fielding其他文献
Nutrition and the biology of human ageing: Bone health & osteoporosis / sarcopenia / immune deficiency
营养与人类衰老的生物学:骨骼健康
- DOI:
- 发表时间:
2013 - 期刊:
- 影响因子:0
- 作者:
E. Offord;L. Karagounis;K. Vidal;Roger A. Fielding;S. Meydani;Josef M. Penninger - 通讯作者:
Josef M. Penninger
Creatine supplementation and age influence muscle metabolism during exercise.
肌酸补充和年龄会影响运动过程中的肌肉代谢。
- DOI:
- 发表时间:
1998 - 期刊:
- 影响因子:3.3
- 作者:
Sinclair A. Smith;S. Montain;R. Matott;G. Zientara;F. Jolesz;Roger A. Fielding - 通讯作者:
Roger A. Fielding
Risk of mortality in older adults with loss of appetite: An analysis of Medicare fee-for-service data.
食欲不振的老年人的死亡风险:医疗保险服务收费数据分析。
- DOI:
10.1016/j.jnha.2023.100035 - 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Simon Dagenais;Sunday Clark;Roger A. Fielding;Cera Cantu;Sapna Prasad;Feng Dai;John D Groarke - 通讯作者:
John D Groarke
Marginal protein intake results in reduced plasma IGF-I levels and skeletal muscle fiber atrophy in elderly women.
边缘蛋白质摄入量会导致老年女性血浆 IGF-I 水平降低和骨骼肌纤维萎缩。
- DOI:
- 发表时间:
2000 - 期刊:
- 影响因子:0
- 作者:
C. Castaneda;Patricia L. Gordon;Roger A. Fielding;W. J. Evans;M. C. Crim - 通讯作者:
M. C. Crim
Sarcopenia Trials in Specific Diseases: Report by the International Conference on Frailty and Sarcopenia Research Task Force.
特定疾病中的肌肉减少症试验:国际衰弱和肌肉减少症研究工作组会议的报告。
- DOI:
- 发表时间:
2016 - 期刊:
- 影响因子:0
- 作者:
Bruno Vellas;Roger A. Fielding;Shalender Bhasin;F. Cerreta;B. Goodpaster;J. Guralnik;S. Kritchevsky;V. Legrand;C. Forkin;Jay Magaziner;John E. Morley;Leocadio Rodríguez;R. Roubenoff;Stephanie A. Studenski;Dennis T. Villareal;Matteo Cesari - 通讯作者:
Matteo Cesari
Roger A. Fielding的其他文献
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{{ truncateString('Roger A. Fielding', 18)}}的其他基金
Activity-dependent signaling in aging skeletal muscle
衰老骨骼肌中的活动依赖性信号传导
- 批准号:
6989263 - 财政年份:2005
- 资助金额:
$ 7.18万 - 项目类别:
LOWER EXTREMITY MUSCLE POWER AND FUNCTION IN THE ELDERLY
老年人下肢肌肉的力量和功能
- 批准号:
7206250 - 财政年份:2004
- 资助金额:
$ 7.18万 - 项目类别:
Lower Extremity Muscle Power and Function in the Elderly
老年人下肢肌肉的力量和功能
- 批准号:
7042168 - 财政年份:2003
- 资助金额:
$ 7.18万 - 项目类别:
LOWER EXTREMITY MUSCLE POWER AND FUNCTION IN THE ELDERLY
老年人下肢肌肉的力量和功能
- 批准号:
6509943 - 财政年份:2001
- 资助金额:
$ 7.18万 - 项目类别:
Lower Extremity Muscle Power and Function in the Elderly
老年人下肢肌肉的力量和功能
- 批准号:
6930285 - 财政年份:2001
- 资助金额:
$ 7.18万 - 项目类别:
LOWER EXTREMITY MUSCLE POWER AND FUNCTION IN THE ELDERLY
老年人下肢肌肉的力量和功能
- 批准号:
6230385 - 财政年份:2001
- 资助金额:
$ 7.18万 - 项目类别:
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