Ciliary neurotrophic factor and strength

老年人的肌肉力量和肌肉质量随着年龄的增长而减少(骨量减少)，以及随着力量训练而增加，这些都有很好的文献记载，但这些反应在个体之间有很大的不同。这种巨大的个体间差异，以及双胞胎研究表明，力量差异的主要原因是遗传因素，这表明遗传因素可能解释了年龄和力量训练导致的力量反应差异的很大一部分原因。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)基因的一种常见多态，在一项对19-95岁的男性和女性进行的横断面研究中，该多态是与年龄相关的力量水平的显著预测因子，并提示证据表明，这种变异与10年期间力量下降的个体间差异有关。这项研究建议检验假设：1)在50-80岁的男性中，CNTF基因座的“零”等位基因与更大的力量水平相关；2)“零”等位基因与7年随访期内较小的力量下降相关。这些研究将在风暴队列中进行，其优点是样本量大，年龄分布应最大限度地扩大所观察到的强度下降，这种下降在50岁及以上时变得显著。最后，在一项针对大学老年男性和女性的干预试验中，我们将检验这一假设，即与普通等位基因相比，CNTF“零”等位基因与中等强度力量训练干预后肌肉力量的增加更大相关。运动干预将结合1998-1999年进行的干预研究的结果，并将额外招募60名受试者。这些研究可能会发现一种基因变异，可以用来预测谁有患骨质疏松症的风险，以及谁将从力量训练干预中受益最大，以预防骨质疏松症。

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.