Sex-related differences in neuromuscular and biological adaptations to power training in older adults The role of creatine supplementation
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Abstract
The aim of the present study was to analyze the modulatory role of sex in neuromuscular and biological adaptations induced by a power training program in older adults, as well as to explore the potential additional effect of creatine supplementation. A total of 99 participants (47 men and 52 women; 67.93 ± 1.30 years) were randomly assigned to training or control conditions, with or without supplementation. Neuromuscular performance was assessed through knee extension at 180°/s, together with biomarkers related to neuroplasticity (brain-derived neurotrophic factor [BDNF]), inflammation (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNF-α]), and enzymatic antioxidant defense (glutathione peroxidase [GPx]), before and after the intervention. Power training induced significant improvements in neuromuscular performance, with large to very large effect sizes. At the biological level, consistent adaptations were observed, characterized by increases in BDNF and GPx activity and reductions in IL-6, whereas TNF-α showed a more moderate and variable response. Regarding sex differences, differential patterns were identified in the neuromuscular response, with variations in the magnitude of adaptation between men and women depending on the supplementation condition. In contrast, biological responses were generally similar between sexes, although specific trends were observed in some biomarkers. Overall, the results suggest that sex acts as a modulator of neuromuscular adaptations to power training in older adults, whereas biological adaptations appear to be more homogeneous. Creatine supplementation may exert a modest but consistent enhancing effect on some responses, although its contribution seems secondary to the exercise stimulus.
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References
Arazi, H., Eghbali, E., & Suzuki, K. (2021). Creatine supplementation, physical exercise and oxidative stress markers: A review of the mechanisms and effectiveness. Nutrients, 13(3), 869. https://doi.org/10.3390/nu13030869 DOI: https://doi.org/10.3390/nu13030869
Bohannon, R. W. (2008). Hand-grip dynamometry predicts future outcomes in aging adults. Journal of Geriatric Physical Therapy, 31(1), 3-10. https://doi.org/10.1519/00139143-200831010-00002 DOI: https://doi.org/10.1519/00139143-200831010-00002
Candow, D. G., Forbes, S. C., Kirk, B., & Duque, G. (2021). Current evidence and possible future applications of creatine supplementation for older adults. Nutrients, 13(3), 745. https://doi.org/10.3390/nu13030745 DOI: https://doi.org/10.3390/nu13030745
Candow, D. G., Ostojic, S. M., Chilibeck, P. D., Longobardi, I., Gualano, B., Tarnopolsky, M. A., Wallimann, T., Moriarty, T., Kreider, R. B., Forbes, S. C., Schlattner, U., & Antonio, J. (2025). Creatine monohydrate supplementation for older adults and clinical populations. Journal of the International Society of Sports Nutrition, 22(sup1), 2534130. https://doi.org/10.1080/15502783.2025.2534130 DOI: https://doi.org/10.1080/15502783.2025.2534130
Clark, B. C., & Manini, T. M. (2012). What is dynapenia? Nutrition, 28(5), 495-503. https://doi.org/10.1016/j.nut.2011.12.002 DOI: https://doi.org/10.1016/j.nut.2011.12.002
Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Routledge.
Colado, J. C., & Triplett, N. T. (2009). Monitoring the intensity of aquatic resistance exercises with devices that increase the drag force: An update. Strength and Conditioning Journal, 31(3), 94-100. https://doi.org/10.1519/SSC.0b013e3181a605b2 DOI: https://doi.org/10.1519/SSC.0b013e3181a605b2
Colado, J. C., García-Massó, X., Rogers, M. E., Tella, V., Benavent, J., & Dantas, E. H. (2012). Effects of aquatic and dry land resistance training devices on body composition and physical capacity in postmenopausal women. Journal of Human Kinetics, 32, 185-195. https://doi.org/10.2478/v10078-012-0035-3 DOI: https://doi.org/10.2478/v10078-012-0035-3
Colado, J. C., Triplett, N. T., Tella, V., Saucedo, P., & Abellán, J. (2009). Effects of aquatic resistance training on health and fitness in postmenopausal women. European Journal of Applied Physiology, 106(1), 113-122. https://doi.org/10.1007/s00421-009-0996-7 DOI: https://doi.org/10.1007/s00421-009-0996-7
Colado, J. C., García-Massó, X., Triplett, N. T., Flandez, J., Borreani, S., & Tella, V. (2012). Concurrent validation of the OMNI-resistance exercise scale of perceived exertion with Thera-Band resistance bands. Journal of Strength and Conditioning Research, 26(11), 3018-3024. https://doi.org/10.1519/JSC.0b013e318245c0c9 DOI: https://doi.org/10.1519/JSC.0b013e318245c0c9
Colado, J. C., Gene-Morales, J., Jiménez-Martínez, P., Hammami, R., Juesas, A., & Babiloni-Lopez, C. (2025). Psychological and physical predictors of perceived effort in elastic band training: A velocity-based approach. International Journal of Sports Physical Therapy, 20(8), 1232-1242. https://doi.org/10.26603/001c.142236 DOI: https://doi.org/10.26603/001c.142236
Critchlow, A. J., Alexander, S. E., Hiam, D. S., Ferrucci, L., Scott, D., & Lamon, S. (2025). Associations between female sex hormones and skeletal muscle ageing: The Baltimore Longitudinal Study of Aging. Journal of Cachexia, Sarcopenia and Muscle, 16(3), e13786. https://doi.org/10.1002/jcsm.13786 DOI: https://doi.org/10.1002/jcsm.13786
Erickson, K. I., Voss, M. W., Prakash, R. S., Basak, C., Szabo, A., Chaddock, L., Kim, J. S., Heo, S., Alves, H., White, S. M., Wojcicki, T. R., Mailey, E., Vieira, V. J., Martin, S. A., Pence, B. D., Woods, J. A., McAuley, E., & Kramer, A. F. (2011). Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences, 108(7), 3017-3022. https://doi.org/10.1073/pnas.1015950108 DOI: https://doi.org/10.1073/pnas.1015950108
Gargallo, P., Tamayo, E., Jiménez-Martínez, P., Juesas, A., Casaña, J., Benítez-Martínez, J. C., Gene-Morales, J., Fernández-Garrido, J., Saez, G. T., & Colado, J. C. (2024). Multicomponent and power training with elastic bands improve metabolic and inflammatory parameters, body composition and anthropometry, and physical function in older women with metabolic syndrome: A 20-week randomized, controlled trial. Experimental Gerontology, 185, 112340. https://doi.org/10.1016/j.exger.2023.112340 DOI: https://doi.org/10.1016/j.exger.2023.112340
Gene-Morales, J., Juesas, A., Saez-Berlanga, A., Martin, E. G., Garrigues-Pelufo, L., Sandoval-Camargo, B. S., Martin-Rivera, F., Chulvi-Medrano, I., Jiménez-Martínez, P., Alix-Fages, C., Gargallo, P., Fernández-Garrido, J., Caballero, O., Jerez-Martínez, A., & Colado, J. C. (2025). Dietary nucleotides enhance neurogenesis, cognitive capacity, muscle function, and body composition in older adults: A randomized, triple-blind, controlled clinical trial. Nutrients, 17(9), 1431. https://doi.org/10.3390/nu17091431 DOI: https://doi.org/10.3390/nu17091431
Gleeson, M., Bishop, N. C., Stensel, D. J., Lindley, M. R., Mastana, S. S., & Nimmo, M. A. (2011). The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nature Reviews Immunology, 11(9), 607-615. https://doi.org/10.1038/nri3041 DOI: https://doi.org/10.1038/nri3041
Gómez-Cabrera, M. C., Domenech, E., & Viña, J. (2008). Moderate exercise is an antioxidant: Upregulation of antioxidant genes by training. Free Radical Biology and Medicine, 44(2), 126-131. https://doi.org/10.1016/j.freeradbiomed.2007.02.001 DOI: https://doi.org/10.1016/j.freeradbiomed.2007.02.001
Hawley, S. E., Bell, Z. W., Huang, Y., Gibbs, J. C., & Churchward-Venne, T. A. (2023). Evaluation of sex-based differences in resistance exercise training-induced changes in muscle mass, strength, and physical performance in healthy older (≥60 y) adults: A systematic review and meta-analysis. Ageing Research Reviews, 91, 102023. https://doi.org/10.1016/j.arr.2023.102023 DOI: https://doi.org/10.1016/j.arr.2023.102023
Hortobágyi, T., Vetrovsky, T., Brach, J. S., van Haren, M., Volesky, K., Radaelli, R., Lopez, P., & Granacher, U. (2023). Effects of Exercise Training on Muscle Quality in Older Individuals: A Systematic Scoping Review with Meta-Analyses. Sports Medicine - Open, 9(1), 41. https://doi.org/10.1186/s40798-023-00585-5 DOI: https://doi.org/10.1186/s40798-023-00585-5
Hunter, S. K. (2014). Sex differences in human fatigability: mechanisms and insight to physiological responses. Acta Physiologica, 210(4), 768-789. https://doi.org/10.1111/apha.12234 DOI: https://doi.org/10.1111/apha.12234
Ji, L. L., Kang, C., & Zhang, Y. (2016). Exercise-induced hormesis and skeletal muscle health. Free Radical Biology and Medicine, 98, 113-122. https://doi.org/10.1016/j.freeradbiomed.2016.02.025 DOI: https://doi.org/10.1016/j.freeradbiomed.2016.02.025
Jones, M. D., Wewege, M. A., Hackett, D. A., Keogh, J. W. L., & Hagstrom, A. D. (2021). Sex Differences in Adaptations in Muscle Strength and Size Following Resistance Training in Older Adults: A Systematic Review and Meta-analysis. Sports Medicine, 51(3), 503-517. https://doi.org/10.1007/s40279-020-01388-4 DOI: https://doi.org/10.1007/s40279-020-01388-4
Juesas, A., Saez-Berlanga, A., Gene-Morales, J., Jiménez-Martínez, P., Alix-Fages, C., Fernández-Garrido, J., Caballero, O., Janicijevic, D., Zarza, V., & Colado, J. C. (2025). Effects of high-resistance elastic band training and a curcumin-based formulation on neuro-oxidative and functional health in sedentary older adults. Healthcare, 13(9), 1055. https://doi.org/10.3390/healthcare13091055 DOI: https://doi.org/10.3390/healthcare13091055
Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., Candow, D. G., Kleiner, S. M., Almada, A. L., & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14, 18. https://doi.org/10.1186/s12970-017-0173-z DOI: https://doi.org/10.1186/s12970-017-0173-z
Liu, C. J., & Latham, N. K. (2009). Progressive resistance strength training for physical disability in older people. Cochrane Database of Systematic Reviews, CD002759. https://doi.org/10.1002/14651858.CD002759 DOI: https://doi.org/10.1002/14651858.CD002759
Mahato, N. K., Davis, A., Simon, J. E., & Clark, B. C. (2024). Assessing muscular power in older adults: evaluating the predictive capacity of the 30-second chair rise test. Frontiers in Aging, 5, 1302574. https://doi.org/10.3389/fragi.2024.1302574 DOI: https://doi.org/10.3389/fragi.2024.1302574
Mattson, M. P., & Arumugam, T. V. (2018). Hallmarks of brain aging: Adaptive and pathological modification by metabolic states. Cell Metabolism, 27(6), 1176-1199. https://doi.org/10.1016/j.cmet.2018.05.011 DOI: https://doi.org/10.1016/j.cmet.2018.05.011
Müller, P., Duderstadt, Y., Lessmann, V., & Müller, N. G. (2020). Lactate and BDNF: Key mediators of exercise induced neuroplasticity? Journal of Clinical Medicine, 9(4), 1136. https://doi.org/10.3390/jcm9041136 DOI: https://doi.org/10.3390/jcm9041136
Newman, A. B., Kupelian, V., Visser, M., Simonsick, E. M., Goodpaster, B. H., Kritchevsky, S. B., Tylavsky, F. A., Rubin, S. M., & Harris, T. B. (2006). Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. Journal of Gerontology A, 61(1), 72-77. https://doi.org/10.1093/gerona/61.1.72 DOI: https://doi.org/10.1093/gerona/61.1.72
Pedersen, B. K. (2019). Physical activity and muscle-brain crosstalk. Nature Reviews Endocrinology, 15(7), 383-392. https://doi.org/10.1038/s41574-019-0174-x DOI: https://doi.org/10.1038/s41574-019-0174-x
Refalo, M. C., Nuckols, G., Galpin, A. J., Gallagher, I. J., Hamilton, D. L., & Fyfe, J. J. (2025). Sex differences in absolute and relative changes in muscle size following resistance training in healthy adults: a systematic review with Bayesian meta-analysis. PeerJ, 13, e19042. https://doi.org/10.7717/peerj.19042 DOI: https://doi.org/10.7717/peerj.19042
Reid, K. F., & Fielding, R. A. (2012). Skeletal muscle power: A critical determinant of physical functioning in older adults. Exercise and Sport Sciences Reviews, 40(1), 4-12. https://doi.org/10.1097/JES.0b013e31823b5f13 DOI: https://doi.org/10.1097/JES.0b013e31823b5f13
Saez-Berlanga, A., Gene-Morales, J., Babiloni-Lopez, C., Jiménez-Martínez, P., Juesas, A., & Colado, J. C. (2026). Optimizing elastic band resistance training for metabolic syndrome components in older adults: A systematic review, meta-analysis, and meta-regression of randomized controlled trials. Archives of Physical Medicine and Rehabilitation. https://doi.org/10.1016/j.apmr.2026.02.485 DOI: https://doi.org/10.1016/j.apmr.2026.02.485
Scharfman, H. E., & MacLusky, N. J. (2006). Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS. Frontiers in Neuroendocrinology, 27(4), 415-435. https://doi.org/10.1016/j.yfrne.2006.09.004 DOI: https://doi.org/10.1016/j.yfrne.2006.09.004
Straub, R. H. (2007). The complex role of estrogens in inflammation. Endocrine Reviews, 28(5), 521-574. https://doi.org/10.1210/er.2007-0001 DOI: https://doi.org/10.1210/er.2007-0001
Tam, R., Mitchell, L., & Forsyth, A. (2025). Does creatine supplementation enhance performance in active females? A systematic review. Nutrients, 17(2), 238. https://doi.org/10.3390/nu17020238 DOI: https://doi.org/10.3390/nu17020238
Tøien, T., Berg, O. K., Modena, R., Brobakken, M. F., & Wang, E. (2025). Heavy strength training in older adults: Implications for health, disease and physical performance. Journal of Cachexia, Sarcopenia and Muscle, 16(2), e13804. https://doi.org/10.1002/jcsm.13804 DOI: https://doi.org/10.1002/jcsm.13804