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.

肌肉力量和肌肉质量随年龄的损失（肌肉减少症）和增益与老年人的力量训练是有据可查的，但这些反应在个体之间差异很大。这种巨大的个体间差异以及双胞胎研究表明， 力量变异的主要部分是由遗传引起的，这表明遗传因素可以解释对衰老和力量训练的力量反应的很大一部分变异。在最近的一项初步研究中，我们观察到睫状神经营养因子（CNTF）基因座的一种常见多态性，这是一项对19-95岁男性和女性进行的横断面研究中与年龄相关的力量水平的重要预测因素，并提示这一点。 变异与10年期间强度下降的个体间变异有关。本研究拟验证以下假设：1）CNTF基因座的“无效”等位基因与50-80岁男性的更高水平的力量相关，2）“无效”等位基因与7年随访期内力量下降较小相关。这些研究将在STORM队列中进行，该队列具有样本量大和年龄小的优点。 分布应最大化观察到的强度下降，这在50岁及以上时变得显著。最后，在一项针对大学生的干预试验中，我们将检验CNTF“无效”等位基因与较大的 与普通等位基因相比，响应于中等强度力量训练干预的肌肉力量增加。运动干预将联合收割机1998-1999年进行的干预研究的结果，并将招募另外60名受试者。这些 研究可以鉴定出一种遗传变异，该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获益最多。