The loss of muscle mass and strength with age (sarcopenia), as well as their gain with strength training(ST), is highly variable among men and women. A significant fraction (30-60%) of inter-individual variability in skeletal muscle phenotypes, including strength, mass, and muscle quality, is due to genetic factors. Identifying those genes that contribute to muscle phenotypes is important in order to assess risk for skeletal muscle dysfunction, especially for the elderly. A major difficulty, however, in pursuing genetic studies in humans is determining which of the 35,000+ genes to screen, given the limited information available for most genes. Consequently, we have used micro array and quantitative PCR techniques to identify 6 candidate genes important to the strength, mass and quality of skeletal muscle in the contexts of age, sex, and ST. Moreover, we have identified 4 additional genes from the literature with known polymorphisms, and have strong preliminary data for three of these genes indicating associations with muscle size and strength in a cohort of elderly men. In the present project, we propose to identify polymorphic variation in the 6 expression-based candidate genes and determine the association of specific alleles and multi-locus genotypes within all 10 candidate genes with baseline measures of muscle strength, mass and quality, as well as ST-induced gains in these phenotypes. We will achieve these aims in two existing cohorts: 1) a cross-sectional cohort of -500 men and women across the adult age span from the Baltimore Longitudinal Study of Aging (BLSA), and 2) a cohort of 100 Caucasian and 100African American men and women (>65 yr.) who have completed a controlled 16 week ST intervention(ERC cohort). The results of this investigation will determine the influence of genetic variation within these biologically plausible candidate genes on muscle phenotypes that can be important limiting factors for physical function in the elderly. The identification of such genes will provide an important foundation for understanding the genetic architecture of muscle phenotypes, with the long-term goal of identifying individuals with genetic susceptibility for sarcopenia.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG021500-01A1
Application #
6678361
Study Section
Special Emphasis Panel (ZRG1-SMB (01))
Program Officer
Carrington, Jill L
Project Start
2003-09-15
Project End
2006-07-31
Budget Start
2003-09-15
Budget End
2004-07-31
Support Year
1
Fiscal Year
2003
Total Cost
$185,413
Indirect Cost
Name
University of Maryland College Park
Department
Miscellaneous
Type
Schools of Public Health
DUNS #
790934285
City
College Park
State
MD
Country
United States
Zip Code
20742
Walsh, Sean; Ludlow, Andrew T; Metter, E Jeffrey et al. (2016) Replication study of the vitamin D receptor (VDR) genotype association with skeletal muscle traits and sarcopenia. Aging Clin Exp Res 28:435-42
Sood, Suchi; Hanson, Erik D; Delmonico, Matthew J et al. (2012) Does insulin-like growth factor 1 genotype influence muscle power response to strength training in older men and women? Eur J Appl Physiol 112:743-53
Sheppard, Ryan L; Spangenburg, Espen E; Chin, Eva R et al. (2011) Androgen receptor polyglutamine repeat length affects receptor activity and C2C12 cell development. Physiol Genomics 43:1135-43
Roth, Stephen M; Walsh, Sean; Liu, Dongmei et al. (2008) The ACTN3 R577X nonsense allele is under-represented in elite-level strength athletes. Eur J Hum Genet 16:391-4
Walsh, Sean; Liu, Dongmei; Metter, E Jeffrey et al. (2008) ACTN3 genotype is associated with muscle phenotypes in women across the adult age span. J Appl Physiol 105:1486-91
Liu, Dongmei; Metter, E Jeffrey; Ferrucci, Luigi et al. (2008) TNF promoter polymorphisms associated with muscle phenotypes in humans. J Appl Physiol 105:859-67
Charbonneau, David E; Hanson, Erik D; Ludlow, Andrew T et al. (2008) ACE genotype and the muscle hypertrophic and strength responses to strength training. Med Sci Sports Exerc 40:677-83
Hand, Brian D; Kostek, Matthew C; Ferrell, Robert E et al. (2007) Influence of promoter region variants of insulin-like growth factor pathway genes on the strength-training response of muscle phenotypes in older adults. J Appl Physiol 103:1678-87
Delmonico, Matthew J; Kostek, Matthew C; Doldo, Neil A et al. (2007) Alpha-actinin-3 (ACTN3) R577X polymorphism influences knee extensor peak power response to strength training in older men and women. J Gerontol A Biol Sci Med Sci 62:206-12
Yao, Lili; Delmonico, Mathew J; Roth, Stephen M et al. (2007) Adrenergic receptor genotype influence on midthigh intermuscular fat response to strength training in middle-aged and older adults. J Gerontol A Biol Sci Med Sci 62:658-63

Showing the most recent 10 out of 13 publications