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LJMU Research Online Baumert, P, Lake, MJ, Stewart, CE, Drust, B and Erskine, RM Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing. http://researchonline.ljmu.ac.uk/3804/ Article Citation (please note it is advisable to refer to the publisher s version if you intend to cite from this work) Baumert, P, Lake, MJ, Stewart, CE, Drust, B and Erskine, RM (2016) Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing. EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY. ISSN 1439-6319 LJMU has developed LJMU Research Online for users to access the research output of the University more effectively. Copyright and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in LJMU Research Online to facilitate their private study or for non-commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain. The version presented here may differ from the published version or from the version of the record. Please see the repository URL above for details on accessing the published version and note that access may require a subscription. For more information please contact researchonline@ljmu.ac.uk http://researchonline.ljmu.ac.uk/

Inter-individual variability in the response to maximal eccentric exercise Philipp Baumert 1, Mark J. Lake 1, Claire E. Stewart 1, Barry Drust 1 and Robert M. Erskine 1,2 1 School of Sport and Exercise Science, Liverpool John Moores University, Liverpool, UK; 2 Institute of Sport, Exercise & Health, University College London, London, UK. Address for correspondence: Dr Robert M. Erskine, School of Sport and Exercise Science, Liverpool John Moores University, Liverpool, L3 3AF, United Kingdom; Telephone: +44 (0)151 904 6256; Fax: +44 (0)151 904 6284; Email: R.M.Erskine@ljmu.ac.uk

We thank Prof. Jones and Prof. Newham for raising useful points of discussion concerning our review on the genetic association with exercise-induced muscle damage (Baumert et al. 2016). As Jones and Newham state, the inter-individual variability in elbow flexor strength loss following eccentric exercise in the study by Newham et al. (1987) (n = 8) appears to be low. Other studies, however, have demonstrated large variation in strength loss following maximal eccentric exercise. For example, Nosaka and Clarkson (1996) (n = 14) observed a 36-74% decrement in maximum elbow flexor strength immediately after eccentric exercise, while Miles et al. (2008) (n = 51) reported a 31 ± 20% (mean ± SD) loss in strength. In our laboratory, we have observed an even greater range of responses (0 to 80% strength loss) following maximal eccentric contractions in the quadriceps in over 60 untrained participants (unpublished data). Finally, in a study by Clarkson et al. (2005) (n = 157), the loss of elbow flexor strength immediately after eccentric exercise was ~49% ± ~2% (SEM), i.e. apparently similar to that found by Newham et al. (1987), but the standard deviation was ~25%. Thus, the results from these studies highlight the importance of large sample sizes to get a more complete picture of the inter-individual variability in strength loss following maximal eccentric exercise. As discussed in our review (Baumert et al. 2016), there is evidence for a genetic association with the initial phase of exercise-induced muscle damage, i.e. the mechanical disruption of the muscle fibre. For example, alpha-actinin-3, a structural protein linking the actin filaments to the Z-disk in type II skeletal muscle fibres, cannot be produced by ACTN3 XX homozygotes, and these individuals appear to be more susceptible to exercise-induced muscle damage (Vincent et al. 2010), although this may be dependent on the mode of exercise (Baumert et al. 2016). In addition to influencing the initial damage response (and therefore indirectly impacting on secondary damage responses), we agree with Jones and Newham that genetic variation is

likely to have a direct influence on the inflammatory response (possibly including the expression of heat shock proteins) and muscle regeneration following eccentric exercise. If a person is genetically predisposed to produce a greater inflammatory response, they may or may not demonstrate a quicker recovery, depending on whether the inflammation is indeed increasing the rate of muscle regeneration and recovery or further degrading damaged muscle fibres and prolonging recovery. In our review (Baumert et al. 2016), we categorised the evidence for a genetic association with exercise-induced muscle damage according to the different phases of the damage response, and we believe that the secondary and regeneration phases are of equal importance to the initial damage response.

References Baumert P, Lake MJ, Stewart CE, Drust B, Erskine RM (2016) Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing. Eur J Appl Physiol:1-31 Clarkson PM, Hoffman EP, Zambraski E, Gordish-Dressman H, Kearns A, Hubal M, Harmon B, Devaney JM (2005) ACTN3 and MLCK genotype associations with exertional muscle damage. J Appl Physiol (1985) 99 (2):564-569. doi:10.1152/japplphysiol.00130.2005 Miles MP, Andring JM, Pearson SD, Gordon LK, Kasper C, Depner CM, Kidd JR (2008) Diurnal variation, response to eccentric exercise, and association of inflammatory mediators with muscle damage variables. J Appl Physiol 104 (2):451-458 Newham D, Jones D, Clarkson P (1987) Repeated high-force eccentric exercise: effects on muscle pain and damage. J Appl Physiol 63 (4):1381-1386 Nosaka K, Clarkson PM (1996) Changes in indicators of inflammation after eccentric exercise of the elbow flexors. Med Sci Sports Exerc 28 (8):953-961 Vincent B, Windelinckx A, Nielens H, Ramaekers M, Van Leemputte M, Hespel P, Thomis MA (2010) Protective role of α-actinin-3 in the response to an acute eccentric exercise bout. J Appl Physiol 109 (2):564-573