Ciliary neurotrophic factor and strength

睫状神经营养因子和强度

• 批准号: 6352668
• 负责人: Robert Edward Ferrell
• 金额: $ 11.42万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6352668
• 关键词: age difference; clinical research; exercise; genetic polymorphism; genetic susceptibility; human genetic material tag; human old age (65+); human subject; human therapy evaluation; muscle strength; neurotrophic factors; sarcopenia; 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 inter-individual 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.

随着年龄的增长，肌肉力量和肌肉质量的损失（肌肉减少症）和在老年人中的力量训练中的增长有充分的文献记载，但这些反应在个体中的差异很大。这种个体间的较大的变异性以及双胞胎研究表明，强度方差的很大一部分是通过遗传来解释的，这表明遗传因素可能解释了对衰老和力量训练的强度响应的很大一部分。在最近的一项试点研究中，我们观察到在睫状神经营养因子（CNTF）基因座上的常见多态性，该基因座是19-95岁的男性和女性的横断面研究中与年龄相关强度水平的重要预测指标，并且是建议的证据。这种差异与十年内强度下降的个体差异有关。这项研究建议检验假设：1）CNTF基因座的“无效”等位基因与50-80岁的男性和2）“无效”等位基因与强度较小相关的强度有关在7年的随访期内。这些研究将在风暴队列中进行，该研究具有较大的样本量和年龄分布的优势，该年龄分布应最大化观察到的强度下降，大约50岁及以上。最后，在对大学老年男性和女性的干预试验中，我们将检验以下假设：与普通等位基因相比，CNTF“无效”等位基因与中等强度强度训练干预措施相比，肌肉力量的增长较大。运动干预将结合1999年至1999年进行的干预研究的结果，并将招募另外60名受试者。这些研究可能会确定一种遗传变异，可用于预测谁有肌肉减少症的风险，谁将从力量训练干预措施中受益最大以预防肌肉减少症。