Abstract
Sarcopenia, which is characterized by a progressive decrease of skeletal muscle mass and function with aging, is closely related to several common diseases (such as cardiovascular and airway diseases) and functional impairment/disability. Strong genetic determination has been reported for muscle mass and muscle strength, two most commonly recognized and studied risk phenotypes for sarcopenia, with heritability ranging from 30 to 85% for muscle strength and 45–90% for muscle mass. Sarcopenia has been the subject of increasing genetic research over the past decade. This review is designed to comprehensively summarize the most important and representative molecular genetic studies designed to identify genetic factors associated with sarcopenia. We have methodically reviewed whole-genome linkage studies in humans, quantitative trait loci mapping in animal models, candidate gene association studies, newly reported genome-wide association studies, DNA microarrays and microRNA studies of sarcopenia or related skeletal muscle phenotypes. The major results of each study are tabulated for easy comparison and reference. The findings of representative studies are discussed with respect to their influence on our present understanding of the genetics of sarcopenia. This is a comprehensive review of molecular genetic studies of gene identification for sarcopenia, and an overarching theme for this review is that the currently accumulating results are tentative and occasionally inconsistent and should be interpreted with caution pending further investigation. Consequently, this overview should enhance recognition of the need to validate/replicate the genetic variants underlying sarcopenia in large human cohorts and animal. We believe that further progress in understanding the genetic etiology of sarcopenia will provide valuable insights into important fundamental biological mechanisms underlying muscle physiology that will ultimately lead to improved ability to recognize individuals at risk for developing sarcopenia and our ability to treat this debilitating condition.
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References
Abney M, McPeek MS, Ober C (2001) Broad and narrow heritabilities of quantitative traits in a founder population. Am J Hum Genet 68:1302–1307
Allen DL, Loh AS (2011) Posttranscriptional mechanisms involving microRNA-27a and b contribute to fast-specific and glucocorticoid-mediated myostatin expression in skeletal muscle. Am J Physiol Cell Physiol 300:C124–C137
Anderson C, Catoe H, Werner R (2006) MIR-206 regulates connexin43 expression during skeletal muscle development. Nucleic Acids Res 34:5863–5871
Arden NK, Spector TD (1997) Genetic influences on muscle strength, lean body mass, and bone mineral density: a twin study. J Bone Miner Res 12:2076–2081
Arking DE, Fallin DM, Fried LP, Li T, Beamer BA, Xue QL, Chakravarti A, Walston J (2006) Variation in the ciliary neurotrophic factor gene and muscle strength in older Caucasian women. J Am Geriatr Soc 54:823–826
Barany M (1967) ATPase activity of myosin correlated with speed of muscle shortening. J Gen Physiol 50(Suppl):197–218
Barr R, Macdonald H, Stewart A, McGuigan F, Rogers A, Eastell R, Felsenberg D, Glüer C, Roux C, Reid DM (2010) Association between vitamin D receptor gene polymorphisms, falls, balance and muscle power: results from two independent studies (APOSS and OPUS). Osteoporos Int 21:457–466
Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, Garry PJ, Lindeman RD (1998) Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 147:755–763
Baumgartner RN, Waters DL, Gallagher D (1999) Predictors of skeletal musclemass in elderly men and women. Mech Ageing Dev 107:123–136
Borecki IB, Higgins M, Schreiner PJ, Arnett DK, Mayer-Davis E, Hunt SC, Province MA (1998) Evidence for multiple determinants of the body mass index: the National Heart, Lung, and Blood Institute Family Heart Study. Obes Res 6:107–114
Bortoli S, Renault V, Eveno E, Auffray C, Butler-Browne G, Pietu G (2003) Gene expression profiling of human satellite cells during muscular aging using cDNA arrays. Gene 321:145–154
Bustamante-Ara N, Santiago C, Verde Z, Yvert T, Gómez-Gallego F, Rodríguez-Romo G, González-Gil P, Serra-Rexach JA, Ruiz JR, Lucia A (2010) ACE and ACTN3 genes and muscle phenotypes in nonagenarians. Int J Sports Med 31:221–224
Cardinali B, Castellani L, Fasanaro P, Basso A, Alema S, Martelli F, Falcone G (2009) Microrna-221 and microrna-222 modulate differentiation and maturation of skeletal muscle cells. PLoS One 4:e7607
Caretti G, Di PM, Micales B, Lyons GE, Sartorelli V (2004) The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation. Genes Dev 18:2627–2638
Carmelli D, Reed T (2000) Stability and change in genetic and environmental influences on hand-grip strength in older male twins. J Appl Physiol 89:1879–1883
Caroni P, Schneider C, Kiefer MC, Zapf J (1994) Role of muscle insulin-like growth factors in nerve sprouting: suppression of terminal sprouting in paralyzed muscle by IGF-binding protein 4. J Cell Biol 125:893–902
Chagnon YC, Chung WK, Perusse L, Chagnon M, Leibel RL, Bouchard C (1999) Linkages and associations between the leptin receptor (LEPR) gene and human body composition in the Quebec Family Study. Int J Obes Relat Metab Disord 23:278–286
Chagnon YC, Borecki IB, Perusse L, Roy S, Lacaille M, Chagnon M, Ho-Kim MA, Rice T, Province MA, Rao DC, Bouchard C (2000) Genome-wide search for genes related to the fat-free body mass in the Quebec Family Study. Metabolism 49:203–207
Chagnon YC, Rice T, Pérusse L, Borecki IB, Ho-Kim MA, Lacaille M, Paré C, Bouchard L, Gagnon J, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C (2001) HERITAGE Family Study genomic scan for genes affecting body composition before and after training in Caucasians from HERITAGE. J Appl Physiol 90:1777–1787
Charbonneau DE, Hanson ED, Ludlow AT, Delmonico MJ, Hurley BF, Roth SHM (2008) ACE genotype and the muscle hypertrophic and strength responses to strength training. Med Sci Sports Exerc 40:677–683
Chen CZ, Lodish HF (2005) MicroRNAs as regulators of mammalian hematopoiesis. Semin Immunol 17:155–165
Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38:228–233
Clarkson PM, Devaney JM, Gordish-Dressman H, Thompson PD, Hubal MJ, Urso M, Price TB, Angelopoulos TJ, Gordon PM, Moyna NM, Pescatello LS, Visich PS, Zoeller RF, Seip RL, Hoffman EP (2005) ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women. J Appl Physiol 99:154–163
Clop A, Marcq F, Takeda H, Pirottin D, Tordoir X, Bibe B, Bouix J, Caiment F, Elsen JM, Eychenne F, Larzul C, Laville E, Meish F, Milenkovic D, Tobin J, Charlier C, Georges M (2006) A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nat Genet 38:813–818
Collins CA, Olsen I, Zammit PS, Heslop L, Petrie A, Partridge TA, Morgan JE (2005) Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell 122:289–301
Conley KE, Jubrias SA, Esselman PC (2000) Oxidative capacity and ageing in human muscle. J Physiol 526 Pt 1:203–210
Corsi AM, Ferrucci L, Gozzini A, Tanini A, Brandi ML (2002) Myostatin polymorphisms and age-related sarcopenia in the Italian population. J Am Geriatr Soc 50:1463
Crist CG, Montarras D, Pallafacchina G, Rocancourt D, Cumano A, Conway SJ, Buckingham M (2009) Muscle stem cell behavior is modified by microRNA-27 regulation of Pax3 expression. Proc Natl Acad Sci USA 106:13383–13387
Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinková E, Vandewoude M, Zamboni M (2010) European Working Group on Sarcopenia in Older People Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing 39:412–423
Danser AHJ, Schalekamp MADH, Bax WA, Vandenbrink AM, Saxena PR, Riegger GAJ, Schunkert H (1995) Angiotensin-converting enzyme in the human heart—effect of the deletion insertion polymorphism. Circulation 92:1387–1388
De Mars G, Windelinckx A, Beunen G, Delecluse C, Lefevre J, Thomis MAI (2007) Polymorphisms in the CNTF and CNTF receptor genes are associated with muscle strength in men and women. J Appl Physiol 102:1824–1831
De Mars G, Windelinckx A, Huygens W, Peeters MW, Beunen GP, Aerssens J, Vlietinck R, Thomis MA (2008a) Genome-wide linkage scan for maximum and length-dependent knee muscle strength in young men: significant evidence for linkage at chromosome 14q24.3. J Med Genet 45:275–283
De Mars G, Windelinckx A, Huygens W, Peeters MW, Beunen GP, Aerssens J, Vlietinck R, Thomis MA (2008b) Genome-wide linkage scan for contraction velocity characteristics of knee musculature in the Leuven Genes for Muscular Strength Study. Physiol Genomics 35:36–44
Dedoussis GVZ, Manios Y, Choumerianou DM, Yiannakouris N, Panagiotakos DB, Skenderi K, Zampelas A (2004) The IL-6 gene G-174C polymorphism related to health indices in Greek primary school children. Obes Res 12:1037–1041
Degens H (1998) Age-related changes in the microcirculation of skeletal muscle. Adv Exp Med Biol 454:343–348
Delbono O, O’Rourke KS, Ettinger WH (1995) Excitation-calcium release uncoupling in aged single human skeletal muscle fibers. J Membr Biol 148:211–222
Delmonico MJ, Kostek MC, Doldo NA, Hand BD, Walsh S, Conway JM, Carignan CR, Roth SM, Hurley BF (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 62:206–212
Delmonico MJ, Zmuda JM, Taylor BC, Cauley JA, Harris TB, Manini TM, Schwartz A, Li R, Roth SM, Hurley BF, Bauer DC, Ferrell RE, Newman A (2008) Association of the ACTN3 genotype and physical functioning with age in older adults. J Gerontol A Biol Sci Med Sci 63:1227–1234
Deng HW, Lai DB, Conway T, Li J, Xu FH, Davies KM, Recker RR (2001) Characterization of genetic and lifestyle factors for determining variation in body mass index, fat mass, percentage of fat mass, and lean mass. J Clin Densitom 4:353–361
Deng FY, Xiao P, Lei SF, Zhang L, Yang F, Tang ZH, Liu PY, Liu YJ, Recker RR, Deng HW (2007) Bivariate whole genome linkage analysis for femoral neck geometric parameters and total body lean mass. J Bone Miner Res 22:808–816
Dennis RA, Przybyla B, Gurley C, Kortebein PM, Simpson P, Sullivan DH, Peterson CA (2008) Aging alters gene expression of growth and remodeling factors in human skeletal muscle both at rest and in response to acute resistance exercise. Physiol Genomics 32:393–400
Dirks AJ, Leeuwenburgh C (2005) The role of apoptosis in age-related skeletal muscle atrophy. Sports Med 35:473–483
Drummond MJ, McCarthy JJ, Fry CS, Esser KA, Rasmussen BB (2008) Aging differentially affects human skeletal muscle microRNA expression at rest and after an anabolic stimulus of resistance exercise and essential amino acids. Am J Physiol Endocrinol Metab 295:E1333–E1340
Endo I, Inoue D, Mitsui T, Umaki Y, Akaike M, Yoshizawa T (2003) Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology 144:5138–5144
Evans W (1997) Functional and metabolic consequences of sarcopenia. J Nutr 127:998S–1003S
Evans WJ (2010) Skeletal muscle loss: cachexia, sarcopenia, and inactivity. Am J Clin Nutr 91:1123S–1127S
Eynon N, Duarte JA, Oliveira J, Sagiv M, Yamin C, Meckel Y, Sagiv M, Goldhammer E (2009) ACTN3 R577X polymorphism and Israeli top-level athletes. Int J Sports Med 30:695–698
Fairbrother UL, Tanko LB, Walley AJ, Christiansen C, Froguel P, Blakemore AIF (2007) Leptin receptor genotype at Gln223Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women. J Bone Miner Res 22:544–550
Ferrell RE, Conte V, Lawrence EC, Roth SM, Hagberg JM, Hurley BF (1999) Frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes. Genomics 62:203–207
Folland J, Leach B, Little T, Hawker K, Myerson S, Montgomery H, Jones D (2000) Angiotensin-converting enzyme genotype affects the response of human skeletal muscle to functional overload. Exp Physiol 85:575–579
Frederiksen H, Gaist D, Petersen HC, Hjelmborg J, McGue M, Vaupel JW, Christensen K (2002) Hand grip strength: a phenotype suitable for identifying genetic variants affecting mid- and late-life physical functioning. Genet Epidemiol 23:110–122
Frederiksen H, Bathum L, Worm C, Christensen K, Puggaard L (2003) ACE genotype and physical training effects: a randomized study among elderly Danes. Aging Clin Exp Res 15:284–291
Galvao DA, Taaffe DR, Spry N, Joseph D, Turner D, Newton RU (2008) Reduced muscle strength and functional performance in men with prostate cancer undergoing androgen suppression: a comprehensive cross-sectional investigation. Prostate Cancer Prostatic Dis 12:198–203
Geusens P, Vandevyver C, Vanhoof J, Cassiman JJ, Boonen S, Raus J (1997) Quadriceps and grip strength are related to vitamin D receptor genotype in elderly nonobese women. J Bone Miner Res 12:2082–2088
Geusens P, Vandevyver C, Stinissen P, Vanhoof J, Raus J, Michiels L (2001) Type I alfa 1 collagen gene polymorphism is associated with bone density, muscle strength and susceptibility for fractures in elderly women. J Bone Miner Res 16:S472
Giaccaglia V, Nicklas B, Kritchevsky S, Mychaleckyz J, Messier S, Bleecker E, Pahor M (2008) Interaction between angiotensin converting enzyme insertion/deletion genotype and exercise training on knee extensor strength in older individuals. Int J Sports Med 29:40–44
Giles JT, Post W, Blumenthal RS, Bathon JM (2006) Therapy insight: managing cardiovascular risk in patients with rheumatoid arthritis. Nat Clin Pract Rheumatol 2:320–329
Gillette-Guyonnet S, Nourhashemi F, Andrieu S, Cantet C, Albarede JL, Vellas B, Grandjean H (2003) Body composition in French women 75+ years of age: the EPIDOS study. Mech Ageing Dev 124:311–316
Giresi PG, Stevenson EJ, Theilhaber J, Koncarevic A, Parkington J, Fielding RA, Kandarian SC (2005) Identification of a molecular signature of sarcopenia. Physiol Genomics 21:253–263
Glass DJ (2005) Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 37:1974–1984
González-Freire M, Rodríguez-Romo G, Santiago C, Bustamante-Ara N, Yvert T, Gómez-Gallego F, Serra Rexach JA, Ruiz JR, Lucia A (2010) The K153R variant in the myostatin gene and sarcopenia at the end of the human lifespan. Age (Dordr) 32:405–409
Gordon SE, Davis BS, Carlson CJ, Booth FW (2001) ANG II is required for optimal overload-induced skeletal muscle hypertrophy. Am J Physiol Endocrinol Metabol 280:E150–E159
Grundberg E, Brandstrom H, Ribom EL, Ljunggren O, Mallmin H, Kindmark A (2004) Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Eur J Endocrinol 150:323–328
Grundberg E, Ribom EL, Brandstrom H, Ljunggren O, Mallmin H, Kindmark A (2005) A TA-repeat polymorphism in the gene for the estrogen receptor alpha does not correlate with muscle strength or body composition in young adult Swedish women. Maturitas 50:153–160
Guadalupe-Grau A, Rodríguez-González FG, Dorado C, Olmedillas H, Fuentes T, Pérez-Gómez J, Delgado-Guerra S, Vicente-Rodríguez G, Ara I, Guerra B, Arteaga-Ortiz R, Calbet JA, Díaz-Chico BN (2010) Androgen receptor gene polymorphisms lean mass and performance in young men. Br J Sports Med (in press)
Hand BD, Kostek MC, Ferrell RE, Delmonico MJ, Douglass LW, Roth SM, Hagberg JM, Hurley BF (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 103:1678–1687
Hawley JA (2009) Molecular responses to strength and endurance training: are they incompatible? Appl Physiol Nutr Metab 34:355–361
Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T, Wichmann HE, Meitinger T, Hunter D, Hu FB, Colditz G, Hinney A, Hebebrand J, Koberwitz K, Zhu X, Cooper R, Ardlie K, Lyon H, Hirschhorn JN, Laird NM, Lenburg ME, Lange C, Christman MF (2006) A common genetic variant is associated with adult and childhood obesity. Science 312:279–283
Hetzel L, Smith A (2001) The 65 years and over population: 2000 (Census 2000 Brief, C2KBR/01-10). Retrieved September 3, 2002, from http://www.census.gov/prod/2001pubs/c2kbrOl-lO.pdf
Hopkinson NS, Nickol AH, Payne J, Hawe E, Man W, Moxham J, Montgomery H, Polkey MI (2004) ACE gene and strength in chronic obstructive pulmonary disease. Am J Resp Crit Care Med 170:395–399
Hopkinson NS, Li KW, Kehoe A, Humphries SE, Roughton M, Moxham J, Montgomery H, Polkey MI (2008) Vitamin D receptor genotypes influence quadriceps strength in chronic obstructive pulmonary disease. Am J Clin Nutr 87:385–390
Houweling PJ, North KN (2009) Sarcomeric α-actinins and their role in human muscle disease. Future Neurol 4:731–743
Hsu FC, Lenchik L, Nicklas BJ, Lohman K, Register TC, Mychaleckyj J, Langefeld CD, Freedman BI, Bowden DW, Carr JJ (2005) Heritability of body composition measured by DXA in the diabetes heart study. Obes Res 13:312–319
Huygens W, Thomis MA, Peeters MW, Aerssens J, Janssen R, Vlietinck RF, Beunen G (2004a) Linkage of myostatin pathway genes with knee strength in humans. Physiol Genomics 17:264–270
Huygens W, Thomis MA, Peeters MW, Aerssens J, Janssen RG, Vlietinck RF, Beunen G (2004b) A quantitative trait locus on 13q14.2 for trunk strength. Twin Res 7:603–606
Huygens W, Thomis MA, Peeters MW, Vlietinck RF, Beunen GP (2004c) Determinants and upper-limit heritabilities of skeletal muscle mass and strength. Can J Appl Physiol 29:186–200
Huygens W, Thomis MA, Peeters MW, Aerssens J, Vlietinck R, Beunen GP (2005) Quantitative trait loci for human muscle strength: linkage analysis of myostatin pathway genes. Physiol Genomics 22:390–397
Iannuzzi-Sucich M, Prestwood KM, Kenny AM (2002) Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol A Biol Sci Med Sci 57:M772–M777
Ishigai Y, Mori T, Ikeda T, Fukuzawa A, Shibano T (1997) Role of bradykinin-NO pathway in prevention of cardiac hypertrophy by ACE inhibitor in rat cardiomyocytes. Am J Physiol Heart Circ Physiol 273:H2659–H2663
Janssen I (2006) Influence of sarcopenia on the development of physical disability: the Cardiovascular Health Study. J Am Geriatr Soc 54:56–62
Janssen I, Shepard DS, Katzmarzyk PT, Roubenoff R (2004) The healthcare costs of sarcopenia in the United States. J Am Geriatr Soc 52:80–85
Jones A, Woods DR (2003) Skeletal muscle RAS and exercise performance. Int J Biochem Cell Biol 35:855–866
Jozsi AC, Dupont-Versteegden EE, Taylor-Jones JM, Evans WJ, Trappe TA, Campbell WW, Peterson CA (2000) Aged human muscle demonstrates an altered gene expression profile consistent with an impaired response to exercise. Mech Ageing Dev 120:45–56
Karasik D, Kiel DP (2008) Genetics of the musculoskeletal system: a pleiotropic approach. J Bone Miner Res 23:788–802
Karasik D, Zhou Y, Cupples LA, Hannan MT, Kiel DP, Demissie S (2009) Bivariate genome-wide linkage analysis of femoral bone traits and leg lean mass: Framingham study. J Bone Miner Res 24:710–718
Kayo T, Allison DB, Weindruch R, Prolla TA (2001) Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys. Proc Natl Acad Sci USA 98:5093–5098
Kenny AM, Mcgee D, Joseph C, Covault J, Abreu C, Raisz LG (2005) Lack of association between androgen receptor polymorphisms and bone mineral density or physical function in older men. Endocr Res 31:285–293
Kim J, Heshka S, Gallagher D, Kotler DP, Mayer L, Albu J, Shen W, Freda PU, Heymsfield SB (2004) Intermuscular adipose tissue-free skeletal muscle mass: estimation by dual-energy X-ray absorptiometry in adults. J Appl Physiol 97:655–660
Kim HK, Lee YS, Sivaprasad U, Malhotra A, Dutta A (2006a) Muscle-specific microRNA miR-206 promotes muscle differentiation. J Cell Biol 174:677–687
Kim J, Shen W, Gallagher D, Jones A Jr, Wang Z, Wang J, Heshka S, Heymsfield SB (2006b) Total-body skeletal muscle mass: estimation by dual-energy X-ray absorptiometry in children and adolescents. Am J Clin Nutr 84:1014–1020
Kostek MC, Delmonico MJ, Reichel JB, Roth SM, Douglass L, Ferrell RE, Hurley BF (2005) Muscle strength response to strength training is influenced by insulin-like growth factor 1 genotype in older adults. J Appl Physiol 98:2147–2154
Kostek MA, Angelopoulos TJ, Clarkson PM, Gordon PM, Moyna NM, Visich PS, Zoeller RF, Price TB, Seip RL, Thompson PD, Devaney JM, Gordish-Dressman H, Hoffman EP, Pescatello LS (2009) Myostatin and follistatin polymorphisms interact with muscle phenotypes and ethnicity. Med Sci Sports Exerc 41:1063–1071
Kostek M, Hubal MJ, Pescatello LS (2011) The role of genetic variation in muscle strength. Am J Lifestyle Med 5:156–170
Kritchevsky SB, Nicklas BJ, Visser M, Simonsick EM, Newman AB, Harris TB, Lange EM, Penninx BW, Goodpaster BH, Satterfield S, Colbert LH, Rubin SM, Pahor M (2005) Angiotensin-converting enzyme insertion/deletion genotype, exercise, and physical decline. JAMA 294:691–698
Kuang W, Tan J, Duan Y, Duan J, Wang W, Jin F, Jin Z, Yuan X, Liu Y (2009) Cyclic stretch induced miR-146a upregulation delays C2C12 myogenic differentiation through inhibition of Numb. Biochem Biophys Res Commun 378:259–263
Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12:735–739
Lapauw B, Goemaere S, Crabbe P, Kaufman JM, Ruige JB (2007) Is the effect of testosterone on body composition modulated by the androgen receptor gene CAG repeat polymorphism in elderly men? Eur J Endocrinol 156:395–401
Larsson L, Li X, Teresi A, Salviati G (1994) Effects of thyroid hormone on fast- and slow-twitch skeletal muscles in young and old rats. J Physiol 481(Pt 1):149–161
Larsson O, Wahlestedt C, Timmons JA (2005) Considerations when using the significance analysis of microarrays (SAM) algorithm. BMC Bioinformatics 6:129
Lau EM, Lynn HS, Woo JW, Kwok TC, Melton LJ III (2005) Prevalence of and risk factors for sarcopenia in elderly Chinese men and women. J Gerontol A Biol Sci Med Sci 60:213–216
Lauretani F, Bandinelli S, Bartali B, Di Iorio A, Giacomini V, Corsi AM, Guralnik JM, Ferrucci L (2006) Axonal degeneration affects muscle density in older men and women. Neurobiol Aging 27:1145–1154
Lecomte E, Herbeth B, Nicaud V, Rakotovao R, Artur Y, Tiret L (1997) Segregation analysis of fat mass and fat-free mass with age- and sex-dependent effects: the Stanislas Family Study. Genet Epidemiol 14:51–62
Lee CK, Klopp RG, Weindruch R, Prolla TA (1999) Gene expression profile of aging and its retardation by caloric restriction. Science 285:1390–1393
Lee SJ, Reed LA, Davies MV, Girgenrath S, Goad ME, Tomkinson KN, Wright JF, Barker C, Ehrmantraut G, Holmstrom J (2005) Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc Natl Acad Sci USA 102:18117–18122
Lee CE, McArdle A, Griffiths RD (2007) The role of hormones, cytokines and heat shock proteins during age-related muscle loss. Clin Nutr 26:524–534
Leger B, Derave W, De Bock K, Hespel P, Russell AP (2008) Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation. Rejuvenation Res 11:163–175B
Lima RM, de Abreu BS, Gentil P, Lima Lins TC, Grattapaglia D, Pereira RW, de Oliveira RJ (2007) Lack of association between vitamin D receptor genotypes and haplotypes with fat-free mass in postmenopausal Brazilian women. J Gerontol A Biol Sci Med Sci 62(9):966–972
Lima RM, Leite TK, Pereira RW, Rabelo HT, Roth SM, Oliveira RJ (2011) ACE and ACTN3 Genotypes in older women: muscular phenotypes. Int J Sports Med 32:66–72
Lionikas A, Blizard DA, Vandenbergh DJ, Glover MG, Stout JT, Vogler GP, McClearn GE, Larsson L (2003) Genetic architecture of fast- and slow-twitch skeletal muscle weight in 200-day-old mice of the C57BL/6J and DBA/2J lineage. Physiol Genomics 16:141–152
Lionikas A, Blizard DA, Gerhard GS, Vandenbergh DJ, Stout JT, Vogler GP, McClearn GE, Larsson L (2005) Genetic determinants of weight of fast- and slow-twitch skeletal muscle in 500-day-old mice of the C57BL/6J and DBA/2J lineage. Physiol Genomics 21:184–192
Lionikas A, Blizard DA, Vandenbergh DJ, Stout JT, Vogler GP, McClearn GE, Larsson L (2006) Genetic determinants of weight of fast- and slow-twitch skeletal muscles in old mice. Mamm Genome 17:615–628
Liu PY, Li YM, Li MX, Malkin I, Qin YJ, Chen XD, Liu YJ, Deng HW (2004a) Lack of evidence for a major gene in the Mendelian transmission of BMI in Chinese. Obes Res 12:1967–1973
Liu YJ, Rocha-Sanchez SMS, Liu PY, Long JR, Lu Y, Elze L, Recker RR, Deng HW (2004b) Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families. Physiological Genomics 17:101–106
Liu DM, Metter EJ, Ferrucci L, Roth SM (2008a) TNF promoter polymorphisms associated with muscle phenotypes in humans. J Appl Physiol 105:859–867
Liu X, Zhao LJ, Liu YJ, Xiong DH, Recker RR, Deng HW (2008b) The MTHFR gene polymorphism is associated with lean body mass but not fat body mass. Hum Genet 123:189–196
Liu XG, Tan LJ, Lei SF, Liu YJ, Shen H, Wang L, Yan H, Guo YF, Xiong DH, Chen XD, Pan F, Yang TL, Zhang YP, Guo Y, Tang NL, Zhu XZ, Deng HY, Levy S, Recker RR, Papasian CJ, Deng HW (2009) Genome-wide association and replication studies identified TRHR as an important gene for lean body mass. Am J Hum Genet 84:418–423
Livshits G, Kato BS, Wilson SG, Spector TD (2007) Linkage of genes to total lean body mass in normal women. J Clin Endocrinol Metab 92:3171–3176
Lopez-Alarcon M, Hunter GR, Gower BA, Fernandez JR (2007) IGF-I polymorphism is associated with lean mass, exercise economy, and exercise performance among premenopausal women. Arch Med Res 38:56–63
Lu J, McKinsey TA, Zhang CL, Olson EN (2000) Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases. Mol Cell 6:233–244
MacArthur DG, Seto JT, Raftery JM, Quinlan KG, Huttley GA, Hook JW, Lemckert FA, Kee AJ, Edwards MR, Berman Y, Hardeman EC, Gunning PW, Easteal S, Yang N, North KN (2007) Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat Genet 39:1261–1265
MacArthur DG, Seto JT, Chan S, Quinlan KG, Raftery JM, Turner N, Nicholson MD, Kee AJ, Hardeman EC, Gunning PW, Cooney GJ, Head SI, Yang N, North KN (2008) An Actn3 knockout mouse provides mechanistic insights into the association between {alpha}-actinin-3 deficiency and human athletic performance. Hum Mol Genet 17:1076–1086
Mahoney DJ, Parise G, Melov S, Safdar A, Tarnopolsky MA (2005) Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise. FASEB J 19:1498–1500
Marvelle AF, Lange LA, Qin L, Adair LS, Mohlke KL (2008) Association of FTO with obesity-related traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) cohort. Diabetes 57:1987–1991
Masinde GL, Li X, Gu W, Davidson H, Hamilton-Ulland M, Wergedal J, Mohan S, Baylink DJ (2002a) Quantitative trait loci (QTL) for lean body mass and body length in MRL/MPJ and SJL/J F(2) mice. Funct Integr Genomics 2:98–104
Masinde GL, Li X, Gu W, Hamilton-Ulland M, Mohan S, Baylink DJ (2002b) Quantitative trait loci that harbor genes regulating muscle size in (MRL/MPJ x SJL/J) F(2) mice. Funct Integr Genomics 2:120–125
Massidda M, Vona G, Calo CM (2009) Association between the ACTN3 R577X polymorphism and artistic gymnastic performance in Italy. Genet Test Mol Biomarkers 13:377–380
McCarthy JJ, Esser KA (2007) MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy. J Appl Physiol 102:306–313
McCauley T, Mastana SS, Hossack J, Macdonald M, Folland JP (2009) Human angiotensin-converting enzyme I/D and alpha-actinin 3 R577X genotypes and muscle functional and contractile properties. Exp Physiol 94:81–89
McCauley T, Mastana SS, Folland JP (2010) ACE I/D and ACTN3 R/X polymorphisms and muscle function and muscularity of older Caucasian men. Eur J Appl Physiol 109:269–277
McPherron AC, Lawler AM (1997) Lee SJ: regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387:83–90
Melov S, Tarnopolsky MA, Beckman K, Felkey K, Hubbard A (2007) Resistance exercise reverses aging in human skeletal muscle. PLoS One 2:e465
Melton LJ III, Khosla S, Crowson CS, O’Connor MK, O’Fallon WM, Riggs BL (2000) Epidemiology of sarcopenia. J Am Geriatr Soc 48:625–630
Middelbos IS, Vester BM, Karr-Lilienthal LK, Schook LB, Swanson KS (2009) Age and diet affect gene expression profile in canine skeletal muscle. PLoS One 4:e4481
Mikkola TM, Sipilä S, Rantanen T, Sievänen H, Suominen H, Tiainen K, Kaprio J, Koskenvuo M, Kauppinen M, Heinonen A (2009) Muscle cross-sectional area and structural bone strength share genetic and environmental effects in older women. J Bone Miner Res 24:338–345
Moran CN, Vassilopoulos C, Tsiokanos A, Jamurtas AZ, Bailey ME, Montgomery HE, Wilson RH, Pitsiladis YP (2006) The associations of ACE polymorphisms with physical, physiological and skill parameters in adolescents. Eur J Hum Genet 14:332–339
Murphy KT, Koopman R, Naim T, Leger B, Trieu J, Ibebunjo C, Lynch GS (2010) Antibody-directed myostatin inhibition in 21-months-old mice reveals novel roles for myostatin signaling in skeletal muscle structure and function. FASEB J 24:4433–4442
Muscaritoli M, Anker SD, Argilés J, Aversa Z, Bauer JM, Biolo G, Boirie Y, Bosaeus I, Cederholm T, Costelli P, Fearon KC, Laviano A, Maggio M, Rossi Fanelli F, Schneider SM, Schols A, Sieber CC (2010) Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics”. Clin Nutr 29:154–159
Naguibneva I, meyar-Zazoua M, Polesskaya A, it-Si-Ali S, Groisman R, Souidi M, Cuvellier S, Harel-Bellan A (2006) The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat Cell Biol 8:278–284
Nair KS (1995) Muscle protein turnover: methodological issues and the effect of aging. J Gerontol A Biol Sci Med Sci 50 Spec No:107–112
Naya FJ, Olson E (1999) MEF2: a transcriptional target for signaling pathways controlling skeletal muscle growth and differentiation. Curr Opin Cell Biol 11:683–688
Newman AB, Kupelian V, Visser M, Simonsick E, Goodpaster B, Nevitt M, Kritchevsky SB, Tylavsky FA, Rubin SM, Harris TB (2003) Sarcopenia: alternative definitions and associations with lower extremity function. J Am Geriatr Soc 51:1602–1609
Nielsen TL, Hagen C, Wraae K, Bathum L, Larsen R, Brixen K, Andersen M (2010) The impact of the CAG repeat polymorphism of the androgen receptor gene on muscle and adipose tissues in 20–29-year-old Danish men: Odense Androgen Study. Eur J Endocrinol 162:795–804
Norman B, Esbjornsson M, Rundqvist H, Osterlund T, von WF, Tesch PA (2009) Strength, power, fiber types, and mRNA expression in trained men and women with different ACTN3 R577X genotypes. J Appl Physiol 106:959–965
North KN, Yang N, Wattanasirichaigoon D, Mills M, Easteal S, Beggs AH (1999) A common nonsense mutation results in alpha-actinin-3 deficiency in the general population. Nat Genet 21:353–354
Onder G, Capoluongo E, Danese P, Settanni S, Russo A, Concolino P, Bernabei R, Landi F (2008) Vitamin D receptor polymorphisms and falls among older adults living in the community: results from the ilSIRENTE study. J Bone Miner Res 23:1031–1036
Park SK, Prolla TA (2005) Gene expression profiling studies of aging in cardiac and skeletal muscles. Cardiovasc Res 66:205–212
Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Muller P, Spring J, Srinivasan A, Fishman M, Finnerty J, Corbo J, Levine M, Leahy P, Davidson E, Ruvkun G (2000) Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408:86–89
Pattison JS, Folk LC, Madsen RW, Childs TE, Booth FW (2003) Transcriptional profiling identifies extensive downregulation of extracellular matrix gene expression in sarcopenic rat soleus muscle. Physiol Genomics 15:34–43
Pescatello LS, Kostek MA, Gordish-Dressman H, Thompson PD, Seip RL, Price TB, Angelopoulos TJ, Clarkson PM, Gordon PM, Moyna NM, Visich PS, Zoeller RF, Devaney JM, Hoffman EP (2006) ACE ID genotype and the muscle strength and size response to unilateral resistance training. Med Sci Sports Exerc 38:1074–1081
Philip B, Lu Z, Gao Y (2005) Regulation of GDF-8 signaling by the p38 MAPK. Cell Signal 17:365–375
Pistilli EE, Gordish-Dressman H, Seip RL, Devaney JM, Thompson PD, Price TB, Angelopoulos TJ, Clarkson PM, Moyna NM, Pescatello LS, Visich PS, Zoeller RF, Hoffman EP, Gordon PM (2007) Resistin polymorphisms are associated with muscle, bone, and fat phenotypes in white men and women. Obesity (Silver Spring) 15:392–402
Potthoff MJ, Olson EN, Bassel-Duby R (2007) Skeletal muscle remodeling. Curr Opin Rheumatol 19:542–549
Pownall ME, Gustafsson MK, Emerson CP Jr (2002) Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos. Annu Rev Cell Dev Biol 18:747–783
Prior SJ, Roth SM, Wang X, Kammerer C, Miljkovic-Gacic I, Bunker CH, Wheeler VW, Patrick AL, Zmuda JM (2007) Genetic and environmental influences on skeletal muscle phenotypes as a function of age and sex in large, multigenerational families of African heritage. J Appl Physiol 103:1121–1127
Purcell S, Cherny SS, Sham PC (2003) Genetic power calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19:149–150
Rao PK, Kumar RM, Farkhondeh M, Baskerville S, Lodish HF (2006) Myogenic factors that regulate expression of muscle-specific microRNAs. Proc Natl Acad Sci USA 103:8721–8726
Rebbapragada A, Benchabane H, Wrana JL, Celeste AJ (2003) Attisano L: myostatin signals through a transforming growth factor beta-like signaling pathway to block adipogenesis. Mol Cell Biol 23:7230–7242
Reecy JM, Spurlock DM, Stahl CH (2006) Gene expression profiling: insights into skeletal muscle growth and development. J Anim Sci 84(Suppl):E150–E154
Rice T, Borecki IB, Bouchard C, Rao DC (1993) Segregation analysis of fat mass and other body composition measures derived from underwater weighing. Am J Hum Genet 52:967–973
Roberts SB (1995) Effects of aging on energy requirements and the control of food intake in men. J Gerontol A Biol Sci Med Sci 50 Spec No:101–106
Rodríguez-Romo G, Ruiz JR, Santiago C, Fiuza-Luces C, González-Freire M, Gómez-Gallego F, Morán M, Lucia A (2010) Does the ACE I/D polymorphism, alone or in combination with the ACTN3 R577X polymorphism, influence muscle power phenotypes in young, non-athletic adults? Eur J Appl Physiol 110:1099–1106
Rosenberg MI, Georges SA, Asawachaicharn A, Analau E, Tapscott SJ (2006) MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206. J Cell Biol 175:77–85
Roth SM, Schrager MA, Ferrell RE, Riechman SE, Metter EJ, Lynch NA, Lindle RS, Hurley BF (2001) CNTF genotype is associated with muscular strength and quality in humans across the adult age span. J Appl Physiol 90:1205–1210
Roth SM, Ferrell RE, Peters DG, Metter EJ, Hurley BF, Rogers MA (2002) Influence of age, sex, and strength training on human muscle gene expression determined by microarray. Physiol Genomics 10:181–190
Roth SM, Metter EJ, Lee MR, Hurley BF, Ferrell RE (2003a) C174T polymorphism in the CNTF receptor gene is associated with fat-free mass in men and women. J Appl Physiol 95:1425–1430
Roth SM, Schrager MA, Lee MR, Metter EJ, Hurley BF, Ferrell RE (2003b) Interleukin-6 (IL6) genotype is associated with fat-free mass in men but not women. J Gerontol A Biol Sci Med Sci 58:B1085–B1088
Roth SM, Zmuda JM, Cauley JA, Shea PR, Ferrell RE (2004) Vitamin D receptor genotype is associated with fat-free mass and sarcopenia in elderly men. J Gerontol A Biol Sci Med Sci 59:10–15
Roubenoff R (2000) Sarcopenic obesity: does muscle loss cause fat gain? Lessons from rheumatoid arthritis and osteoarthritis. Ann N Y Acad Sci 904:553–557
Roubenoff R (2004) Sarcopenic obesity: the confluence of two epidemics. Obes Res 12:887–888
Roubenoff R, Heymsfield SB, Kehayias JJ, Cannon JG, Rosenberg IH (1997) Standardization of nomenclature of body composition in weight loss. Am J Clin Nutr 66:192–196
Sabourin LA, Rudnicki MA (2000) The molecular regulation of myogenesis. Clin Genet 57:16–25
Salmen T, Heikkinen AM, Mahonen A, Kroger H, Komulainen M, Saarikoski S, Honkanen R, Partanen J, Maenpaa PH (2002) Relation of estrogen receptor-alpha gene polymorphism and hormone replacement therapy to fall risk and muscle strength in early postmenopausal women. Ann Med 34:64–72
San Juan AF, Gomez-Gallego F, Canete S, Santiago C, Perez M, Lucia A (2006) Does complete deficiency of muscle alpha actinin 3 alter functional capacity in elderly women? A preliminary report. Br J Sports Med 40:e1
Santiago C, Ruiz JR, Rodríguez-Romo G, Fiuza-Luces C, Yvert T, Gonzalez-Freire M, Gómez-Gallego F, Morán M, Lucia A (2011) The K153R polymorphism in the myostatin gene and muscle power phenotypes in young, non-athletic men. PLoS One 6:e16323
Sayer AA, Syddall H, O’Dell SD, Chen XH, Briggs PJ, Briggs R, Day IN, Cooper C (2002) Polymorphism of the IGF2 gene, birth weight and grip strength in adult men. Age Ageing 31:468–470
Schrager MA, Roth SM, Ferrell RE, Metter EJ, Russek-Cohen E, Lynch NA, Lindle RS, Hurley BF (2004) Insulin-like growth factor-2 genotype, fat-free mass, and muscle performance across the adult life span. J Appl Physiol 97:2176–2183
Seibert MJ, Xue QL, Fried LP, Walston JD (2001) Polymorphic variation in the human myostatin (GDF-8) gene and association with strength measures in the Women’s Health and Aging Study II cohort. J Am Geriatr Soc 49:1093–1096
Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5:R13
Sermet-Gaudelus I, Souberbielle JC, Azhar I, Ruiz JC, Magnine P, Colomb V, Le BC, Folio D, Lenoir G (2003) Insulin-like growth factor I correlates with lean body mass in cystic fibrosis patients. Arch Dis Child 88:956–961
Siu PM, Pistilli EE, Alway SE (2008) Age-dependent increase in oxidative stress in gastrocnemius muscle with unloading. J Appl Physiol 105(6):1695–1705
Smyth DJ, Cooper JD, Bailey R, Field S, Burren O, Smink LJ, Guja C, Ionescu-Tirgoviste C, Widmer B, Dunger DB, Savage DA, Walker NM, Clayton DG, Todd JA (2006) A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Nat Genet 38:617–619
Sokol NS, Ambros V (2005) Mesodermally expressed Drosophila microRNA-1 is regulated by Twist and is required in muscles during larval growth. Genes Dev 19:2343–2354
Stepto NK, Coffey VG, Carey AL, Ponnampalam AP, Canny BJ, Powell D, Hawley JA (2009) Global gene expression in skeletal muscle from well-trained strength and endurance athletes. Med Sci Sports Exerc 41:546–565
Sun G, Gagnon J, Chagnon Y, Perusse L, Despres J, Leon A, Wilmore J, Skinner J, Borecki I, Rao D, Bouchard C (1999) Association and linkage between an insulin-like growth factor-1 gene polymorphism and fat free mass in the HERITAGE Family Study. Int J Obes 23:929–935
Szulc P, Beck TJ, Marchand F, Delmas PD (2005) Low skeletal muscle mass is associated with poor structural parameters of bone and impaired balance in elderly men—the MINOS study. J Bone Miner Res 20:721–729
Tan RS, Culberson JW (2003) An integrative review on current evidence of testosterone replacement therapy for the andropause. Maturitas 45:15–27
Teran-Garcia M, Rankinen T, Koza RA, Rao DC, Bouchard C (2005) Endurance training-induced changes in insulin sensitivity and gene expression. Am J Physiol Endocrinol Metab 288:E1168–E1178
Thomas DC, Haile RW, Duggan D (2005) Recent developments in genomewide association scans: a workshop summary and review. Am J Hum Genet 77:337–345
Thomas LB, Harrison AL, Stemple JC (2007) Aging thyroarytenoid and limb skeletal muscle: lessons in contrast. J Voice 22:430–450
Thomis MA, Beunen GP, Van Leemputte M, Maes HH, Blimkie CJ, Claessens AL, Marchal G, Willems E, Vlietinck RF (1998) Inheritance of static and dynamic arm strength and some of its determinants. Acta Physiol Scand 163:59–71
Thomis MA, Huygens W, Heuninckx S, Chagnon M, Maes HH, Claessens AL, Vlietinck R, Bouchard C, Beunen GP (2004) Exploration of myostatin polymorphisms and the angiotensin-converting enzyme insertion/deletion genotype in responses of human muscle to strength training. Eur J Appl Physiol 92:267–274
Tiainen K, Sipila S, Alen M, Heikkinen E, Kaprio J, Koskenvuo M, Tolvanen A, Pajala S, Rantanen T (2004) Heritability of maximal isometric muscle strength in older female twins. J Appl Physiol 96:173–180
Tiainen K, Sipila¨ S, Alen M, Heikkinen E, Kaprio J, Koskenvuo M, Tolvanen A, Pajala S, Rantanen T (2005) Shared genetic and environmental effects on strength and power in older female twins. Med Sci Sports Exerc 37:72–78
Tiainen KM, Perola M, Kovanen VM, Sipilä S, Tuononen KA, Rikalainen K, Kauppinen MA, Widen EI, Kaprio J, Rantanen T, Kujala UM (2008) Genetics of maximal walking speed and skeletal muscle characteristics in older women. Twin Res Hum Genet 11:321–334
Tiainen K, Sipilä S, Kauppinen M, Kaprio J, Rantanen T (2009) Genetic and environmental effects on isometric muscle strength and leg extensor power followed up for three years among older female twins. J Appl Physiol 106:1604–1610
Timmons JA, Larsson O, Jansson E, Fischer H, Gustafsson T, Greenhaff PL, Ridden J, Rachman J, Peyrard-Janvid M, Wahlestedt C, Sundberg CJ (2005) Human muscle gene expression responses to endurance training provide a novel perspective on Duchenne muscular dystrophy. FASEB J 19:750–760
Tinsley JM, Potter AC, Phelps SR, Fisher R, Trickett JI, Davies KE (1996) Amelioration of the dystrophic phenotype of mdx mice using a truncated utrophin transgene. Nature 384:349–353
Trendelenburg AU, Meyer A, Rohner D, Boyle J, Hatakeyama S, Glass DJ (2009) Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am J Physiol Cell Physiol 296:C1258–C1270
Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 98:5116–5121
Van Pottelbergh I, Goemaere S, Nuytinck L, De Paepe A, Kaufman JM (2001) Association of the type I collagen alpha1 Sp1 polymorphism, bone density and upper limb muscle strength in community-dwelling elderly men. Osteoporos Int 12:895–901
van Rossum EF, Voorhoeve PG, te Velde SJ, Koper JW, Delemarre-van de Waal HA, Kemper HC, Lamberts SW (2004) The ER22/23EK polymorphism in the glucocorticoid receptor gene is associated with a beneficial body composition and muscle strength in young adults. J Clin Endocrinol Metab 89:4004–4009
Vigano A, Trutschnigg B, Kilgour RD, Hamel N, Hornby L, Lucar E, Foulkes W, Tremblay ML, Morais JA (2009) Relationship between angiotensin-converting enzyme gene polymorphism and body composition, functional performance, and blood biomarkers in advanced cancer patients. Clin Cancer Res 15:2442–2447
Vincent B, De Bock K, Ramaekers M, Van den EE, Van Leemputte M, Hespel P, Thomis MA (2007) ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics 32:58–63
Visser M (2009) Towards a definition of sarcopenia–results from epidemiologic studies. Nutr Health Aging 13:713–716
von Wnuck LK, Keul P, Lucke S, Heusch G, Wohlschlaeger J, Baba HA, Levkau B (2006) Degraded collagen induces calpain-mediated apoptosis and destruction of the X-chromosome-linked inhibitor of apoptosis (xIAP) in human vascular smooth muscle cells. Cardiovasc Res 69:697–705
Wagner H, Thaller S, Dahse R, Sust M (2006) Biomechanical muscle properties and angiotensin-converting enzyme gene polymorphism: a model-based study. Eur J Appl Physiol 98:507–515
Walsh S, Zmuda JM, Cauley JA, Shea PR, Metter EJ, Hurley BF, Ferrell RE, Roth SM (2005) Androgen receptor CAG repeat polymorphism is associated with fat-free mass in men. J Appl Physiol 98:132–137
Walsh S, Metter EJ, Ferrucci L, Roth SM (2007) Activin-type II receptor B (ACVR2B) and follistatin haplotype associations with muscle mass and strength in humans. J Appl Physiol 102:2142–2148
Walsh S, Liu DM, Metter EJ, Ferrucci L, Roth SM (2008) ACTN3 genotype is associated with muscle phenotypes in women across the adult age span. J Appl Physiol 105:1486–1491
Walsh S, Kelsey BK, Angelopoulos TJ, Clarkson PM, Gordon PM, Moyna NM, Visich PS, Zoeller RF, Seip RL, Bilbie S, Thompson PD, Hoffman EP, Price TB, Devaney JM, Pescatello LS (2009) CNTF 1357 G ->A polymorphism and the muscle strength response to resistance training. J Appl Physiol 107:1235–1240
Walston J, Arking DE, Fallin D, Li T, Beamer B, Xue Q, Ferrucci L, Fried LP, Chakravarti A (2005) IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women. Exp Gerontol 40:344–352
Wang P, Ma L, Zhao B, Wang H, Tan S, Feng L, Ma R (2003) Elite Chinese power athletes and CNTF (ciliary neurotrophic factor) genetic polymorphism. Med Sci Sports Exer 35
Wang P, Ma LH, Wang HY, Zhang W, Tian Q, Cao DN, Zheng GX, Sun YL (2006) Association between polymorphisms of vitamin D receptor gene Apal, Bsml and Taql and muscular strength in young Chinese women. Int J Sports Med 27:182–186
Wang H, Garzon R, Sun H, Ladner KJ, Singh R, Dahlman J, Cheng A, Hall BM, Qualman SJ, Chandler DS, Croce CM, Guttridge DC (2008a) NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell 14:369–381
Wang XL, Deng FY, Tan LJ, Deng HY, Liu YZ, Papasian CJ, Recker RR, Deng HW (2008b) Bivariate whole genome linkage analyses for total body lean mass and BMD. J Bone Miner Res 23:447–452
Wang H, Sun H, Guttridge DC (2009a) microRNAs: novel components in a muscle gene regulatory network. Cell Cycle 8:1833–1837
Wang Y, O’Connell JR, McArdle PF, Wade JB, Dorff SE, Shah SJ, Shi X, Pan L, Rampersaud E, Shen H, Kim JD, Subramanya AR, Steinle NI, Parsa A, Ober CC, Welling PA, Chakravarti A, Weder AB, Cooper RS, Mitchell BD, Shuldiner AR, Chang YP (2009b) From the cover: whole-genome association study identifies STK39 as a hypertension susceptibility gene. Proc Natl Acad Sci USA 106:226–231
Welle S, Bhatt K, Thornton CA (2000) High-abundance mRNAs in human muscle: comparison between young and old. J Appl Physiol 89:297–304
Welle S, Brooks AI, Delehanty JM, Needler N, Thornton CA (2003) Gene expression profile of aging in human muscle. Physiol Genomics 14:149–159
Welle S, Brooks AI, Delehanty JM, Needler N, Bhatt K, Shah B, Thornton CA (2004) Skeletal muscle gene expression profiles in 20–29 year old and 65–71 year old women. Exp Gerontol 39:369–377
Whittemore LA, Song K, Li X, Aghajanian J, Davies M, Girgenrath S, Hill JJ, Jalenak M, Kelley P, Knight A, Maylor R, O’Hara D, Pearson A, Quazi A, Ryerson S, Tan XY, Tomkinson KN, Veldman GM, Widom A, Wright JF, Wudyka S, Zhao L, Wolfman NM (2003) Inhibition of myostatin in adult mice increases skeletal muscle mass and strength. Biochem Biophys Res Commun 300:965–971
Williams AG, Day SH, Folland JP, Gohlke P, Dhamrait S, Montgomery HE (2005) Circulating angiotensin converting enzyme activity is correlated with muscle strength. Med Sci Sports Exerc 37:944–948
Windelinckx A, De Mars G, Beunen G, Aerssens J, Delecluse C, Lefevre J, Thomis MA (2007) Polymorphisms in the vitamin D receptor gene are associated with muscle strength in men and women. Osteoporos Int 18:1235–1242
Windelinckx A, De Mars G, Huygens W, Peeters MW, Vincent B, Wijmenga C, Lambrechts D, Delecluse C, Roth SM, Metter EJ, Ferrucci L, Aerssens J, Vlietinck R, Beunen GP, Thomis MA (2011) Comprehensive fine mapping of chr12q12–14 and follow-up replication identify activin receptor 1B (ACVR1B) as a muscle strength gene. Eur J Hum Genet 19:208–215
Wittwer M, Billeter R, Hoppeler H, Fluck M (2004) Regulatory gene expression in skeletal muscle of highly endurance-trained humans. Acta Physiol Scand 180:217–227
Wong CF, Tellam RL (2008) MicroRNA-26a targets the histone methyltransferase Enhancer of Zeste homolog 2 during myogenesis. J Biol Chem 283:9836–9843
Woods D, Onambele G, Woledge R, Skelton D, Bruce S, Humphries SE, Montgomery H (2001) Angiotensin-I converting enzyme genotype-dependent benefit from hormone replacement therapy in isometric muscle strength and bone mineral density. J Clin Endocrinol Metab 86:2200–2204
Xiong DH, Liu XG, Guo YF, Tan LJ, Wang L, Sha BY, Tang ZH, Pan F, Yang TL, Chen XD, Lei SF, Yerges LM, Zhu XZ, Wheeler VW, Patrick AL, Bunker CH, Guo Y, Yan H, Pei YF, Zhang YP, Levy S, Papasian CJ, Xiao P, Lundberg YW, Recker RR, Liu YZ, Liu YJ, Zmuda JM, Deng HW (2009) Genome-wide association and follow-up replication studies identified ADAMTS18 and TGFBR3 as bone mass candidate genes in different ethnic groups. Am J Hum Genet 84:388–398
Brazilian women J Gerontol A Biol Sci Med Sci 62:966–972
Yamamoto M, Kuroiwa A (2003) Hoxa-11 and Hoxa-13 are involved in repression of MyoD during limb muscle development. Dev Growth Differ 45:485–498
Yamin C, Amir O, Sagiv M, Attias E, Meckel Y, Eynon N, Sagiv M, Amir RE (2007) ACE ID genotype affects blood creatine kinase response to eccentric exercise. J Appl Physiol 103:2057–2061
Yang N, Garton F, North K (2009) Alpha-actinin-3 and performance. Med Sport Sci 54:88–101
Yoshihara A, Tobina T, Yamaga T, Ayabe M, Yoshitake Y, Kimura Y, Shimada M, Nishimuta M, Nakagawa N, Ohashi M, Hanada N, Tanaka H, Kiyonaga A, Miyazaki H (2009) Physical function is weakly associated with angiotensin-converting enzyme gene I/D polymorphism in elderly Japanese subjects. Gerontology 55:387–392
Yoshioka M, Tanaka H, Shono N, Snyder EE, Shindo M, St-Amand J (2003) Serial analysis of gene expression in the skeletal muscle of endurance athletes compared to sedentary men. FASEB J 17:1812–1819
Yoshioka M, Tanaka H, Shono N, Shindo M, St-Amand J (2007) Gene expression profile of sprinter’s muscle. Int J Sports Med 28:1053–1058
Zahn JM, Sonu R, Vogel H, Crane E, Mazan-Mamczarz K, Rabkin R, Davis RW, Becker KG, Owen AB, Kim SK (2006) Transcriptional profiling of aging in human muscle reveals a common aging signature. PLoS Genet 2:e115
Zang H, Davis SR (2008) Androgen replacement therapy in androgen-deficient women with hypopituitarism. Drugs 68:2085–2093
Zempo H, Tanabe K, Murakami H, Iemitsu M, Maeda S, Kuno S (2010) ACTN3 polymorphism affects thigh muscle area. Int J Sports Med 31:138–142
Zhai G, Stankovich J, Ding C, Scott F, Cicuttini F, Jones G (2004) The genetic contribution to muscle strength, knee pain, cartilage volume, bone size, and radiographic osteoarthritis: a sibpair study. Arthritis Rheum 50:805–810
Zhai G, Ding C, Stankovich J, Cicuttini F, Jones G (2005) The genetic contribution to longitudinal changes in knee structure and muscle strength: a sibpair study. Arthritis Rheum 52:2830–2834
Zhao LJ, Xiao P, Liu YJ, Xiong DH, Shen H, Recker RR, Deng HW (2007) A genome-wide linkage scan for quantitative trait loci underlying obesity related phenotypes in 434 Caucasian families. Hum Genet 121:145–148
Zitzmann M, Gromoll J, von Eckardstein A, Nieschlag E (2003) The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men. Diabetologia 46:31–39
Acknowledgments
The study was partially supported by the Natural Science Foundation of China (NSFC) (30771222, 30900810), NSFC—Canadian Institutes of Health Research (CIHR) Joint Health Research Initiative Proposal (30811120436), NSFC/RGC Joint Research Scheme (30731160618), Shanghai Leading Academic Discipline Project (S30501), a grant from Ministry of Education to ShangHai University of Science and Technology and startup fund from the University of Shanghai for Science and Technology. HWD was partially supported by grants from NIH (R01 AR050496-01, R21 AG027110, R01 AG026564, P50 AR055081 and R01 AR057049).
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The authors L.-J. Tan and S.-L. Liu contributed equally to this study.
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Tan, LJ., Liu, SL., Lei, SF. et al. Molecular genetic studies of gene identification for sarcopenia. Hum Genet 131, 1–31 (2012). https://doi.org/10.1007/s00439-011-1040-7
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DOI: https://doi.org/10.1007/s00439-011-1040-7