SARCOPENIA--UNDERLYING MECHANISMS

肌肉减少症--潜在机制

• 批准号: 6805390
• 负责人: BARRY R DWORKIN
• 金额: $ 31.44万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6805390
• 关键词: actins; aging; clinical research; gender difference; glycosylation; human middle age (35-64); human old age (65+); human subject; human very old age (85+); magnetic resonance imaging; muscle contraction; myosins; oxidative stress; posttranslational modifications; sarcopenia; young adult human (21-34)

The demographic evolution in the US, with an increasing number of elderly citizens, is probably the single most important socio- economic challenge to the American health care system, both today and in the future perspective. A number of diseases associated with aging have received intense scientific attention, such as Alzheimer's disease, diabetes mellitus, Parkinson's disease, osteoporosis, and others. The aging-related motor handicap and the impaired neuromuscular function in old age, on the other hand, have received relatively less scientific interest, especially studies bridging the gap between basic science and clinical practice. This is surprising, since slowing of movements and muscle weakness are prominent features of old age in most mammals, and by far the most commonly encountered type of muscle atrophy in man is that associated with senility. Thus, improving functional independence has become an important goal as the elderly population increases, and it is well accepted that while individuals may live longer, they do not necessarily live active, happy and independent lives. This project is the first of its kind where state-of-the-art techniques are used to study the mechanisms underlying aging- related impairments in muscle function from the whole muscle to the cellular and molecular levels in humans, and how they are affected by gender. Specific interest is focused on aging- related post-translational modifications of the motor protein myosin by oxidative stress and non-enzymatic glycosylation (glycation), and the consequences of these modifications on regulation of muscle contraction. This is of significant interest since antioxidant defense system and other intracellular factors which affect glycation may become less efficient in the aged organism. The use of whole muscle, cellular- and molecular physiological methods in combination with ultrasensitive electrophoretic protein separation, imaging and immuno/enzyme- histochemical techniques offers a unique possibility to explore the regulatory and modulatory influence of the molecular motor protein myosin on contractile speed and how this regulation is affected by aging in humans. This research project will elucidate basic mechanisms underlying the motor handicap in the elderly at the skeletal muscle level and apply this knowledge to clinical research/practice, aiming to improve the quality of life and to decrease the dependency of the increasing population of elderly US citizens.

在美国越来越多的老年公民的人口发展可能是当今和未来的观点，可能是美国医疗保健系统最重要的社会经济挑战。 与衰老有关的许多疾病受到了激烈的科学关注，例如阿尔茨海默氏病，糖尿病，米洛蒂斯，帕金森氏病，骨质疏松症等。 另一方面，与衰老相关的运动障碍和老年神经肌肉功能受损的科学兴趣相对较少，尤其是弥合基础科学与临床实践之间差距的研究。 这是令人惊讶的，因为在大多数哺乳动物中，运动和肌肉无力的放缓是老年的重要特征，而到目前为止，人类最常见的肌肉萎缩类型是与衰老有关的。 因此，随着老年人口的增加，提高功能独立性已成为一个重要目标，尽管人们可以寿命更长，但他们不一定会过着活跃，幸福和独立的生活。该项目是第一个使用最新技术来研究肌肉功能与肌肉功能相关的机制，从整个肌肉到人类细胞和分子水平，以及它们如何受性别影响。 特定的兴趣集中在通过氧化应激和非酶糖基化（糖基化）（糖基化）以及这些修饰对调节肌肉收缩的后果的衰老相关后翻译后修饰。 这引起了重大兴趣，因为抗氧化剂防御系统和其他影响糖化的细胞内因子可能在老年生物体中效率较低。 整个肌肉，细胞和分子生理方法的使用与超敏感的电泳蛋白分离，成像和免疫/酶 - 组织化学技术相结合，提供了一种独特的可能性，可以探索探索分子汽车蛋白质蛋白质蛋白质蛋白质对收缩速度和这种调节的调节性影响，并受到这种调节的影响。该研究项目将阐明在骨骼肌水平上老年人的运动障碍的基本机制，并将这些知识应用于临床研究/实践，旨在改善生活质量并减少美国老年公民人口增长的依赖性。

项目成果

Human skeletal muscle myosin function at physiological and non-physiological temperatures.

人类骨骼肌肌球蛋白在生理和非生理温度下发挥作用。

• DOI: 10.1111/j.1748-1716.2005.01516.x
• 发表时间: 2006
• 期刊: Acta physiologica (Oxford, England)
• 作者: Lionikas,A;Li,M;Larsson,L
• 通讯作者: Larsson,L

Aberrant expression of myosin isoforms in skeletal muscles from mice lacking the rev-erbAalpha orphan receptor gene.

• DOI: 10.1152/ajpregu.00690.2003
• 发表时间: 2005-02
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: P. Pircher;Patrick Chomez;Fushun Yu;Björn Vennström;Lars Larsson

There is no slowing of motility speed with increased body size in rat, human, horse and rhinoceros independent on temperature and skeletal muscle myosin isoform.

大鼠、人类、马和犀牛的运动速度不会随着体型的增加而减慢，与温度和骨骼肌肌球蛋白亚型无关。

• DOI: 10.1111/j.1748-1716.2011.02292.x
• 发表时间: 2011
• 期刊: Acta physiologica (Oxford, England)
• 作者: Li,M;Li,M;Marx,JO;Larsson,L
• 通讯作者: Larsson,L