Ciliary neurotrophic factor and strength

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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.