Ciliary neurotrophic factor and strength

睫状神经营养因子和强度

• 批准号: 6210913
• 负责人: Robert Edward Ferrell
• 金额: $ 14.1万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-25 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6210913
• 关键词: alleles; clinical research; disease /disorder proneness /risk; exercise; genetic polymorphism; human data; human genetic material tag; human old age (65+); human population genetics; human subject; human therapy evaluation; muscle disorders; muscle strength; neurotrophic factors; young adult human (21-34)

Losses of muscular strength and muscle mass with age (sarcopenia) and gains with strength training in the elderly are well documented, but these responses vary substantially among individuals. This large inter-individual variability and the fact that Twin studies show that a major portion of the variance in strength is accounted for by heredity, suggest that genetic factors may explain a large portion of the variation in strength responses to aging and strength training. In a recent pilot study, we observed a common polymorphism at the ciliary neurotrophic factor (CNTF) locus that was a significant predictor of age-associated strength levels in a cross-sectional study of 19-95 year old men and women, and suggestive evidence that this variation was associated with interindividual variation in declines in strength over a 10 year period. This study proposes to test the hypothesis: 1) that the "null" allele at the CNTF locus is associated with greater levels of strength in 50-80 year old men and 2) that the "null" allele is associated with smaller declines in strength over.a 7 year follow-up period. The studies, to be carried out in the STORM cohort, which offers the advantages of a large sample size and an age distribution that should maximize the observed declines in strength, which become significant around 50 years of age and older. Finally, in a intervention trial of college aged males and females, we will test the hypothesis that the CNTF "null" allele is associated with larger gains in muscle strength in response to a moderate intensity strength training intervention compared to the common allele. The exercise intervention will combine results from an intervention study carried out in 1998-1999 and will enroll an additional 60 subjects. These studies may identify a genetic variant which can be used to predict who is at risk of sarcopenia, and who will benefit most from strength training intervention to prevent sarcopenia.

老年人的肌肉力量和肌肉质量随着年龄的增长而下降（肌肉减少症），而随着力量训练的增加，这些情况都有据可查，但这些反应因人而异。这种巨大的个体差异以及双胞胎研究表明， 力量差异的主要部分是由遗传引起的，这表明遗传因素可以解释年龄和力量训练引起的力量反应的大部分差异。在最近的一项试点研究中，我们在一项针对 19-95 岁男性和女性的横断面研究中观察到了睫状神经营养因子 (CNTF) 基因座的常见多态性，该多态性是与年龄相关的力量水平的重要预测因子，并且有提示性证据那个这个 变异与 10 年期间个体间力量下降的差异有关。本研究旨在检验以下假设：1) CNTF 基因座的“无效”等位基因与 50-80 岁男性的较大力量水平相关，2)“无效”等位基因与较小的力量下降相关超过 7 年的随访期。这些研究将在 STORM 队列中进行，具有样本量大和年龄大的优势 分布应最大化观察到的力量下降，这种下降在 50 岁及以上时变得显着。最后，在一项针对大学年龄男性和女性的干预试验中，我们将检验 CNTF“无效”等位基因与较大年龄相关的假设。 与常见等位基因相比，中等强度力量训练干预后肌肉力量的增加。运动干预将结合 1998-1999 年进行的一项干预研究的结果，并将另外招募 60 名受试者。这些 研究可能会发现一种基因变异，可用于预测谁有患肌肉减少症的风险，以及谁将从预防肌肉减少症的力量训练干预中受益最多。