{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:04:10Z","timestamp":1785416650904,"version":"3.56.0"},"reference-count":101,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002569","name":"Wonkwang University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002569","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/006776986","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic musculoskeletal pain and sarcopenia co-occur at rates exceeding epidemiological independence in older adults. However, no systematic review has examined whether exercise-induced myokine signaling suppresses shared NF-\u03baB\u2013driven inflammatory pathways to concurrently address chronic pain and sarcopenic muscle loss in older adults. Following PRISMA 2020 guidelines, we searched PubMed, Web of Science, Scopus, and Embase (January 2000\u2013March 2026) and included 32 studies (RCTs, cohort, cross-sectional, and mechanistic designs) in adults aged \u226545 years with chronic musculoskeletal pain and\/or sarcopenia; studies lacking an exercise component or human mechanistic relevance were excluded, and findings were qualitatively synthesized. The included studies suggest that persistent NF-\u03baB hyperactivation\u2014driven by SASP, LPS\u2013TLR4 signaling, and mitochondrial ROS\u2014is associated with both sarcopenic muscle loss and pain sensitization. Evidence from included studies indicates that contracting skeletal muscle secretes IL-6, IL-15, irisin, BDNF, and myostatin, which were frequently associated with suppression of NF-\u03baB activity, attenuation of NLRP3 inflammasome activation, and improvement in pain inhibition\u2014suggesting a hypothesized shared mechanistic pathway that awaits direct validation in trials enrolling older adults with co-confirmed sarcopenia and chronic pain. Multicomponent training emerged as the modality most consistently associated with concurrent benefits for both conditions across included studies. The synthesized evidence supports considering a two-phase approach\u2014pain neuroscience education followed by progressive resistance training\u2014as a hypothesis-driven framework to improve exercise adherence and myokine responses. These findings suggest that myokine signaling represents a plausible shared mechanistic pathway linking exercise to concurrent improvements in sarcopenia and chronic pain, warranting direct validation in future trials.<\/jats:p>","DOI":"10.3390\/ijms27125204","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T09:46:54Z","timestamp":1780998414000},"page":"5204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Myokine Signaling in Sarcopenia-Associated Chronic Musculoskeletal Pain: A Systematic Review of Inflammatory Mechanisms"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5902-2237","authenticated-orcid":false,"given":"Hae Sung","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Physical Education, College of Education, Wonkwang University, 460, Iksan-daero, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ijoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Sport Science, College of Arts and Science, Inha University, 100, Inha-ro, Michuhol-gu, Incheon 22212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Geun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Golf and Leisure, Daegu Technical University, 7, Songhyeon-ro, Dalseo-gu, Daegu 42734, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yae-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Sport Welfare, College of Sport, Kyungil University, 50, Gamnyang-ro, Hayang-eup, Gyeongsan-si 38428, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1080\/03009742.2016.1218543","article-title":"Chronic pain in older adults: Prevalence, incidence, and risk factors","volume":"46","author":"Larsson","year":"2017","journal-title":"Scand. J. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s40200-017-0302-x","article-title":"Prevalence of sarcopenia in the world: A systematic review and meta-analysis of general population studies","volume":"16","author":"Shafiee","year":"2017","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: Revised European consensus on definition and diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.2147\/JPR.S435866","article-title":"Sarcopenia and Chronic Pain in the Elderly: A Systematic Review and Meta-Analysis","volume":"16","author":"Chen","year":"2023","journal-title":"J. Pain Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"250","DOI":"10.4235\/agmr.23.0081","article-title":"The Relationship between Chronic Musculoskeletal Pain and Sarcopenia Risk in Community-Dwelling Older Adults: A Cross-Sectional Study","volume":"27","author":"Sahin","year":"2023","journal-title":"Ann. Geriatr. Med. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Iolascon, G., and Moretti, A. (2026). The sarcopenia-pain connection: Why mechanisms matter for patient care?. Front. Pain Res., 7.","DOI":"10.3389\/fpain.2026.1759943"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1093\/gerona\/glu057","article-title":"Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases","volume":"69","author":"Franceschi","year":"2014","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Fan","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"M326","DOI":"10.1093\/gerona\/57.5.M326","article-title":"Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: The Health ABC Study","volume":"57","author":"Visser","year":"2002","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2384664","DOI":"10.1080\/07853890.2024.2384664","article-title":"Association of interleukin-6 with sarcopenia and its components in older adults: A systematic review and meta-analysis of cross-sectional studies","volume":"56","author":"Ding","year":"2024","journal-title":"Ann. Med."},{"key":"ref_11","first-page":"24","article-title":"Recognizing the Risks of Chronic Nonsteroidal Anti-Inflammatory Drug Use in Older Adults","volume":"18","author":"Marcum","year":"2010","journal-title":"Ann. Longterm Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/art.43073","article-title":"Efficacy of a Tumor Necrosis Factor Inhibitor in Chronic Low-Back Pain with Modic Type 1 Changes: A Randomized Controlled Trial","volume":"77","author":"Gjefsen","year":"2025","journal-title":"Arthritis Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Leal, L.G., Lopes, M.A., and Batista, M.L. (2018). Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01307"},{"key":"ref_14","first-page":"A12220766","article-title":"From the discovery of myokines to exercise as medicine","volume":"70","author":"Pedersen","year":"2023","journal-title":"Dan. Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"520258","DOI":"10.1155\/2010\/520258","article-title":"The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases","volume":"2010","author":"Brandt","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.bbi.2011.02.010","article-title":"Exercise-induced myokines and their role in chronic diseases","volume":"25","author":"Pedersen","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1152\/physrev.90100.2007","article-title":"Muscle as an endocrine organ: Focus on muscle-derived interleukin-6","volume":"88","author":"Pedersen","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1001\/jama.2014.9405","article-title":"Management of persistent pain in the older patient: A clinical review","volume":"312","author":"Makris","year":"2014","journal-title":"JAMA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1136\/gutjnl-2022-327365","article-title":"A mechanism by which gut microbiota elevates permeability and inflammation in obese\/diabetic mice and human gut","volume":"72","author":"Mishra","year":"2023","journal-title":"Gut"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1093\/gerona\/glad062","article-title":"Pain Increases the Risk for Sarcopenia in Community-Dwelling Adults: Results from the English Longitudinal Study of Ageing","volume":"78","author":"Veronese","year":"2023","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"glae080","DOI":"10.1093\/gerona\/glae080","article-title":"Pain Characteristics and Progression to Sarcopenia in Chinese Middle-Aged and Older Adults: A 4-Year Longitudinal Study","volume":"79","author":"Chen","year":"2024","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1093\/gerona\/glad002","article-title":"Association Between Pain and Sarcopenia Among Adults Aged \u226565 Years from Low- and Middle-Income Countries","volume":"78","author":"Smith","year":"2023","journal-title":"J. Gerontol. Ser. A Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.maturitas.2016.11.006","article-title":"Inflammation and sarcopenia: A systematic review and meta-analysis","volume":"96","author":"Bano","year":"2017","journal-title":"Maturitas"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2004.09.027","article-title":"IKKbeta\/NF-kappaB activation causes severe muscle wasting in mice","volume":"119","author":"Cai","year":"2004","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10410","DOI":"10.1523\/JNEUROSCI.2541-04.2004","article-title":"Chronic back pain is associated with decreased prefrontal and thalamic gray matter density","volume":"24","author":"Apkarian","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.pain.2010.07.018","article-title":"Mechanisms involved in IL-6-induced muscular mechanical hyperalgesia in mice","volume":"151","author":"Manjavachi","year":"2010","journal-title":"Pain"},{"key":"ref_28","first-page":"1180","article-title":"Fecal Microbiota Transplantation Attenuates Frailty via Gut-Muscle Axis in Old Mice","volume":"16","author":"Zhu","year":"2024","journal-title":"Aging Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1002\/glia.21056","article-title":"Spinal injection of TNF-\u03b1-activated astrocytes produces persistent pain symptom mechanical allodynia by releasing monocyte chemoattractant protein-1","volume":"58","author":"Gao","year":"2010","journal-title":"Glia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1469-7793.2000.00237.x","article-title":"Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6","volume":"529","author":"Steensberg","year":"2000","journal-title":"J. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fj.01-0507fje","article-title":"Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: Influence of muscle glycogen content","volume":"15","author":"Keller","year":"2001","journal-title":"FASEB J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1006\/excr.2002.5624","article-title":"Overexpression of interleukin-15 induces skeletal muscle hypertrophy: Implications for treatment of muscle wasting disorders","volume":"280","author":"Quinn","year":"2002","journal-title":"Exp. Cell Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.cmet.2013.09.008","article-title":"Exercise induces hippocampal BDNF through a PGC-1\u03b1\/FNDC5 pathway","volume":"18","author":"Wrann","year":"2013","journal-title":"Cell Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1210\/en.2012-1773","article-title":"IL-15 overexpression promotes endurance, oxidative energy metabolism, and muscle PPAR\u03b4, SIRT1, PGC-1\u03b1, and PGC-1\u03b2 expression in male mice","volume":"154","author":"Quinn","year":"2013","journal-title":"Endocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.mad.2009.11.002","article-title":"Exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats","volume":"131","author":"Koltai","year":"2010","journal-title":"Mech. Ageing Dev."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Liu, H.-W., and Chang, S.-J. (2018). Moderate exercise suppresses NF-\u03baB signaling and activates the SIRT1-AMPK-PGC1\u03b1 Axis to attenuate muscle loss in diabetic db\/db mice. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00636"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hu, S., Wu, Z., Liu, X., Ding, Y., Chen, J., and Wang, X. (2025). The role and mechanism of irisin\/NLRP3 signal in aerobic exercise ameliorating blood glucose homeostasis in pre-diabetic mice. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0336395"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4103\/ijpvm.IJPVM_310_17","article-title":"Skeletal Muscle Hypertrophy, Insulin-like Growth Factor 1, Myostatin and Follistatin in Healthy and Sarcopenic Elderly Men: The Effect of Whole-body Resistance Training","volume":"10","author":"Negaresh","year":"2019","journal-title":"Int. J. Prev. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"114272","DOI":"10.1016\/j.physbeh.2023.114272","article-title":"The effects of resistance training on myostatin and follistatin in adults: A systematic review and meta-analysis","volume":"269","author":"Khalafi","year":"2023","journal-title":"Physiol. Behav."},{"key":"ref_40","first-page":"CD002759","article-title":"Progressive resistance strength training for improving physical function in older adults","volume":"2009","author":"Liu","year":"2009","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Wen, K., Zhang, X., and Sun, Y. (2025). Effects of resistance training on muscle mass, strength, and physical function in older women with sarcopenia: A systematic review and meta-analysis. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1735899"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Liao, C.-D., Huang, S.-W., Chen, H.-C., Huang, Y.-Y., Liou, T.-H., and Lin, C.-L. (2023). Effects of Protein Supplementation Combined with Resistance Exercise Training on Walking Speed Recovery in Older Adults with Knee Osteoarthritis and Sarcopenia. Nutrients, 15.","DOI":"10.3390\/nu15071552"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Tayebi, S.M., Poorhabibi, H., Heidary, D., Amini, M.A., and Sadeghi, A. (2025). Impact of aerobic exercise on chronic inflammation in older adults: A systematic review and meta-analysis. BMC Sports Sci. Med. Rehabil., 17.","DOI":"10.1186\/s13102-025-01279-z"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1186\/s13690-024-01441-y","article-title":"The effectiveness of multicomponent exercise in older adults with cognitive frailty: A systematic review and meta-analysis","volume":"82","author":"Luo","year":"2024","journal-title":"Arch. Public Health"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1007\/s12603-021-1665-8","article-title":"International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines","volume":"25","author":"Izquierdo","year":"2021","journal-title":"J. Nutr. Health Aging"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jpain.2020.04.003","article-title":"Exercise-Induced Hypoalgesia in Healthy Individuals and People with Chronic Musculoskeletal Pain: A Systematic Review and Meta-Analysis","volume":"22","author":"Wewege","year":"2021","journal-title":"J. Pain"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Xue, J., Han, X., Zheng, Y., Zhang, Q., and Kong, L. (2024). Effectiveness of resistance training in modulating inflammatory biomarkers among Asian patients with sarcopenia: A systematic review and meta-analysis of randomized controlled trials. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1385902"},{"key":"ref_48","first-page":"603","article-title":"The use of pain neuroscience education in older adults with chronic back and\/or lower extremity pain","volume":"35","author":"Rufa","year":"2019","journal-title":"Physiother. Theory Pract."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"39157","DOI":"10.1038\/s41598-025-23951-7","article-title":"Pain neuroscience education with physical activity improves physical and psychological outcomes in older women with chronic low back pain","volume":"15","author":"Abiko","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1159\/000537936","article-title":"Blood Profiles of Community-Dwelling People with Sarcopenia: Analysis Based on the China Health and Retirement Longitudinal Study","volume":"70","author":"He","year":"2024","journal-title":"Gerontology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.jpain.2017.03.008","article-title":"The Dorsolateral Prefrontal Cortex in Acute and Chronic Pain","volume":"18","author":"Seminowicz","year":"2017","journal-title":"J. Pain"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Kami, K., Tajima, F., and Senba, E. (2022). Brain Mechanisms of Exercise-Induced Hypoalgesia: To Find a Way Out from \u201cFear-Avoidance Belief\u201d. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052886"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1146\/annurev-physiol-020518-114339","article-title":"The physiology of optimizing health with a focus on exercise as medicine","volume":"81","author":"Pedersen","year":"2019","journal-title":"Annu. Rev. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"820","DOI":"10.18632\/aging.100696","article-title":"Dysregulation of SIRT-1 in aging mice increases skeletal muscle fatigue by a PARP-1-dependent mechanism","volume":"6","author":"Mohamed","year":"2014","journal-title":"Aging"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"25","DOI":"10.14336\/AD.2022.0622","article-title":"The Role of Sirtuins in Sarcopenia and Frailty","volume":"14","author":"Anwar","year":"2023","journal-title":"Aging Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1038\/sj.emboj.7600244","article-title":"Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase","volume":"23","author":"Yeung","year":"2004","journal-title":"EMBO J."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yang, H., Zhang, W., Pan, H., Feldser, H.G., Lainez, E., Miller, C., Leung, S., Zhong, Z., Zhao, H., and Sweitzer, S. (2012). SIRT1 Activators Suppress Inflammatory Responses through Promotion of p65 Deacetylation and Inhibition of NF-\u03baB Activity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046364"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1016\/j.bbamcr.2013.04.005","article-title":"Poly (ADP-ribose) polymerase-1-induced NAD+ depletion promotes nuclear factor-\u03baB transcriptional activity by preventing p65 de-acetylation","volume":"1833","author":"Kauppinen","year":"2013","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"R198","DOI":"10.1152\/ajpregu.00325.2009","article-title":"Calcineurin activates interleukin-6 transcription in mouse skeletal muscle in vivo and in C2C12 myotubes in vitro","volume":"298","author":"Allen","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.cmet.2012.12.012","article-title":"Exercise metabolism and the molecular regulation of skeletal muscle adaptation","volume":"17","author":"Egan","year":"2013","journal-title":"Cell Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1152\/japplphysiol.00971.2016","article-title":"Muscle damage and inflammation during recovery from exercise","volume":"122","author":"Peake","year":"2017","journal-title":"J. Appl. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cmet.2017.09.015","article-title":"Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment","volume":"27","author":"Hojman","year":"2018","journal-title":"Cell Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1113\/jphysiol.2006.113175","article-title":"Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle","volume":"576","author":"Dreyer","year":"2006","journal-title":"J. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1007\/s00223-014-9925-9","article-title":"The molecular basis for load-induced skeletal muscle hypertrophy","volume":"96","author":"Marcotte","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"MacKenzie, M.G., Hamilton, D.L., Pepin, M., Patton, A., and Baar, K. (2013). Inhibition of Myostatin Signaling through Notch Activation following Acute Resistance Exercise. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068743"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4361","DOI":"10.1007\/s00018-014-1689-x","article-title":"Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways","volume":"71","author":"Rodriguez","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"C1124","DOI":"10.1152\/ajpcell.00043.2009","article-title":"Myostatin inhibits IGF-I-induced myotube hypertrophy through Akt","volume":"297","author":"Morissette","year":"2009","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/2211-5463.13028","article-title":"Effect of endurance exercise duration on muscle hypertrophy induced by functional overload","volume":"11","author":"Shirai","year":"2021","journal-title":"FEBS Open Bio"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Cui, X., Liu, H., Liu, Y., Yu, Z., Wang, D., Wei, W., and Wang, S. (2025). The role and mechanisms of myokines in sarcopenia: New intervention strategies for the challenges of aging. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1665708"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/crt2.43","article-title":"Skeletal muscle myostatin gene expression and sarcopenia in overweight and obese middle-aged and older adults","volume":"6","author":"Ryan","year":"2021","journal-title":"JCSM Clin. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Cheon, Y.-H., Lee, C.-H., Chung, C.-H., Kim, J.-Y., and Lee, M.-S. (2024). Vigeo Promotes Myotube Differentiation and Protects Dexamethasone-Induced Skeletal Muscle Atrophy via Regulating the Protein Degradation, AKT\/mTOR, and AMPK\/Sirt-1\/PGC1alpha Signaling Pathway In Vitro and In Vivo. Nutrients, 16.","DOI":"10.3390\/nu16162687"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8779","DOI":"10.1002\/fsn3.4550","article-title":"Exploring the Relationship Between Gut Microbiota and Sarcopenia Based on Gut\u2013Muscle Axis","volume":"12","author":"Li","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e2508024","DOI":"10.4014\/jmb.2508.08024","article-title":"Gut Microbiota Modulation by Lacticaseibacillus paracasei EFEL6501 Ameliorates Muscle Atrophy","volume":"35","author":"Pyeon","year":"2025","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41538-025-00698-z","article-title":"Composite dietary fiber alleviates obesity-induced skeletal muscle atrophy by regulating gut microbiota-derived short-chain fatty acids in mice","volume":"10","author":"Xie","year":"2026","journal-title":"npj Sci. Food"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Zhao, M., Zhang, L., and Liu, Z. (2025). Gut microbiota-mediated pain sensitization: Mechanisms and therapeutic implications. Front. Pain Res., 6.","DOI":"10.3389\/fpain.2025.1626515"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s10194-025-02260-4","article-title":"The role of gut microbiota in neuropathic pain: Insights into immune mechanisms","volume":"27","author":"Gong","year":"2025","journal-title":"J. Headache Pain"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Jiang, H., Wang, X., Zhou, W., Huang, Z., and Zhang, W. (2025). Gut microbiota dysbiosis in diabetic nephropathy: Mechanisms and therapeutic targeting via the gut-kidney axis. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1661037"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/jcsm.12129","article-title":"Toll-like receptor 4 signalling mediates inflammation in skeletal muscle of patients with chronic kidney disease","volume":"8","author":"Verzola","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"100045","DOI":"10.1016\/j.ynpai.2020.100045","article-title":"Microbes, microglia, and pain","volume":"7","author":"Kerr","year":"2020","journal-title":"Neurobiol. Pain"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"116769","DOI":"10.1016\/j.biopha.2024.116769","article-title":"Lactobacillus Plantarum intake mitigates neuropathic pain behavior via enhancing macrophage M2 polarization in a rat model of peripheral neuropathy","volume":"175","author":"Huang","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Fang, J., Yan, W., Sun, X., and Chen, J. (2025). The role of exercise-induced short-chain fatty acids in the gut-muscle axis: Implications for sarcopenia prevention and therapy. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1665551"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Min, L., Ablitip, A., Wang, R., Luciana, T., Wei, M., and Ma, X. (2024). Effects of Exercise on Gut Microbiota of Adults: A Systematic Review and Meta-Analysis. Nutrients, 16.","DOI":"10.3390\/nu16071070"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Ren, N., Wang, W.-F., Zou, L., Zhao, Y.-L., Miao, H., and Zhao, Y.-Y. (2024). The nuclear factor kappa B signaling pathway is a master regulator of renal fibrosis. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1335094"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1089\/rej.2015.1671","article-title":"Serum 25-Hydroxyvitamin D and Osteoarthritis in Older People: The Progetto Veneto Anziani Study","volume":"18","author":"Veronese","year":"2015","journal-title":"Rejuvenation Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"111090","DOI":"10.1016\/j.exger.2020.111090","article-title":"The effect of 12-week resistance exercise training on serum levels of cellular aging process parameters in elderly men","volume":"141","author":"Eskandari","year":"2020","journal-title":"Exp. Gerontol."},{"key":"ref_86","first-page":"1075","article-title":"Kinesiophobia and Fear Avoidance in Older Adults: A Scoping Review on the State of Research Activity","volume":"30","author":"Alpalhao","year":"2022","journal-title":"J. Aging Phys. Act."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Larsson, C., Hansson, E.E., Sundquist, K., and Jakobsson, U. (2016). Impact of pain characteristics and fear-avoidance beliefs on physical activity levels among older adults with chronic pain: A population-based, longitudinal study. BMC Geriatr., 16.","DOI":"10.1186\/s12877-016-0224-3"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.neucli.2022.08.001","article-title":"The influence of kinesiophobia and pain catastrophizing on pain-induced corticomotor modulation in healthy participants: A cross sectional study","volume":"52","author":"Duport","year":"2022","journal-title":"Neurophysiol. Clin."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1093\/brain\/awh098","article-title":"Pain catastrophizing and neural responses to pain among persons with fibromyalgia","volume":"127","author":"Gracely","year":"2004","journal-title":"Brain"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"102793","DOI":"10.1016\/j.jelekin.2023.102793","article-title":"Role of kinesiophobia in the selective motor control during gait in patients with low back-related leg pain","volume":"71","author":"Castro","year":"2023","journal-title":"J. Electromyogr. Kinesiol."},{"key":"ref_91","first-page":"13636","article-title":"Levels of catastrophizing pain and kinesiophobia in patients with osteoarthritis and their association","volume":"35","author":"Vitsa","year":"2025","journal-title":"Eur. J. Transl. Myol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/s41531-025-01113-w","article-title":"New perspectives on molecular mechanisms underlying exercise-induced benefits in Parkinson\u2019s disease","volume":"11","author":"Chen","year":"2025","journal-title":"npj Park. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7555\/JBR.37.20230133","article-title":"Irisin\/BDNF signaling in the muscle-brain axis and circadian system: A review","volume":"38","author":"Inyushkin","year":"2023","journal-title":"J. Biomed. Res."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Liu, S., Cui, F., Ning, K., Wang, Z., Fu, P., Wang, D., and Xu, H. (2022). Role of irisin in physiology and pathology. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.962968"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"306","DOI":"10.4103\/NRR.NRR-D-24-01034","article-title":"Aerobic exercise-induced myokine irisin release: A novel strategy to promote neuroprotection and improve cognitive function","volume":"21","author":"Choi","year":"2026","journal-title":"Neural Regen. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"15489","DOI":"10.1038\/srep15489","article-title":"Defective mitochondrial fission augments NLRP3 inflammasome activation","volume":"5","author":"Park","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Alfonso-Loeches, S., Urena-Peralta, J.R., Morillo-Bargues, M.J., Oliver-De La Cruz, J., and Guerri, C. (2014). Role of mitochondria ROS generation in ethanol-induced NLRP3 inflammasome activation and cell death in astroglial cells. Front. Cell. Neurosci., 8.","DOI":"10.3389\/fncel.2014.00216"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Xiong, H.-Y., Hendrix, J., Schabrun, S., Wyns, A., Van Campenhout, J., Nijs, J., and Polli, A. (2024). The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation. Biomolecules, 14.","DOI":"10.3390\/biom14010071"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Long, Y., Xie, X., Wang, Y., Xu, J., Gao, Z., Fang, X., Xu, T., Zhang, N., Lv, D., and Wu, T. (2024). Atrophy patterns in hippocampal subregions and their relationship with cognitive function in fibromyalgia patients with mild cognitive impairment. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1380121"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Liu, Y., Fu, X., Zhao, X., Cui, R., and Yang, W. (2024). The role of exercise-related FNDC5\/irisin in depression. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1461995"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Marmondi, F., Ferrando, V., Filipas, L., Codella, R., Ruggeri, P., La Torre, A., Faelli, E.L., and Bonato, M. (2025). Exercise-Induced Biomarker Modulation in Sarcopenia: From Inflamm-Aging to Muscle Regeneration. Sports, 13.","DOI":"10.3390\/sports13120444"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5204\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:28:56Z","timestamp":1781324936000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":101,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125204"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125204","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]}}}