{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T10:33:53Z","timestamp":1793010833917,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ultra\u2010endurance sports are increasingly popular, yet the long\u2010term physiological consequences of sustained extreme training loads remain poorly understood. In particular, the effects of prolonged ultra\u2010endurance exercise on skeletal muscle structure, function and molecular remodelling are largely unknown. This case study examined a highly experienced ultra\u2010endurance athlete who completed a world\u2010record attempt to run 30\u2009300\u2009km, with extensive phenotyping focusing on skeletal muscle adaptations and recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A 49\u2010year\u2010old male athlete (172\u2009cm, 65\u2009kg) ran ~70\u2009km daily for 15\u2009months. Musculoskeletal, cardiac and visceral ultrasonography, leg muscle strength and power measurements were performed before and after the challenge. Muscle biopsies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094) from\n                      <jats:italic>vastus lateralis<\/jats:italic>\n                      were obtained immediately after completion and during 17\u2009months of recovery to assess myosin heavy chain (MHC) composition, mitochondrial electron transport chain (ETC) complexes and proteins involved in mitochondrial turnover, autophagy and inflammation. Body composition, haematological and biochemical markers, and gut microbiota composition were monitored longitudinally.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The athlete ran 30\u2009300\u2009km over 444\u2009days, maintaining a daily distance of ~70\u2009km despite substantial musculoskeletal discomfort, including a tibial stress reaction mid\u2010challenge, which resolved gradually with continued running. Body mass decreased by ~3\u2009kg, primarily reflecting fat loss (~83%), accompanied by reductions in muscle thickness, maximal strength and power. Circulating creatine kinase (3\u201315\u2010fold), oxidative stress markers (~50%) and GDF8 (~10%\u201350%) were sustainedly increased, whereas IGF\u2010I decreased (~10%\u201340%), suggesting a reduced anabolic environment during the challenge. Muscle biopsy analyses revealed a progressive recovery of mitochondrial function during the 17\u2009months following the challenge, as evidenced by a progressive increase in ETC protein abundance and the expression of regulators of mitochondrial dynamics and quality control (MFN2, PARKIN, DRP1). In contrast, markers of autophagy, apoptosis and inflammation were decreased during the 17\u2010months post\u2010challenge (LC3A\/B\u2010I by ~50%, CASP3 by ~60% and NF\u2010\u03baB\n                      <jats:sup>Ser536<\/jats:sup>\n                      by ~20%). Muscle fibre composition showed extreme predominance of slow fibres (nearly 100% MHC\u2010I), which persisted during recovery. Most molecular and functional alterations gradually resolved within 10\u201317\u2009months. Gut microbiota diversity increased during the challenge, with enrichment of\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      during running and\n                      <jats:italic>Akkermansia<\/jats:italic>\n                      during recovery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sustaining daily ultrarunning for more than 1\u2009year induces substantial skeletal muscle remodelling, including reduced muscle size, impaired contractile function and mitochondrial maladaptations, despite largely preserved endocrine and haematological stability. These findings highlight skeletal muscle as a primary physiological system challenged during extreme endurance exercise and demonstrate that recovery from such perturbations may require more than one year.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70368","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:06:06Z","timestamp":1787983566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Musculoskeletal (Mal)adaptations in Response to a &gt;\u200930\u2009000\u2010km Running Challenge"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1956-6616","authenticated-orcid":false,"given":"Tomas","family":"Venckunas","sequence":"first","affiliation":[{"name":"Institute of Sport Science and Innovations Lithuanian Sports University  Kaunas Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5322-4150","authenticated-orcid":false,"given":"Thomas","family":"Chaillou","sequence":"additional","affiliation":[{"name":"School of Health Sciences \u00d6rebro University  \u00d6rebro Sweden"},{"name":"Institute of Metabolic and Cardiovascular Diseases INSERM\/Universit\u00e9 de Toulouse, Team MetaDiab  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2822-1836","authenticated-orcid":false,"given":"Leonardo","family":"Cesanelli","sequence":"additional","affiliation":[{"name":"Institute of Sport Science and Innovations Lithuanian Sports University  Kaunas Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2008-6150","authenticated-orcid":false,"given":"Danguole","family":"Satkunskiene","sequence":"additional","affiliation":[{"name":"Institute of Sport Science and Innovations Lithuanian Sports University  Kaunas Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saulius","family":"Rutkauskas","sequence":"additional","affiliation":[{"name":"Department of Radiology Lithuanian University of Health Sciences, Medical Academy  Kaunas Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrius","family":"Snieckus","sequence":"additional","affiliation":[{"name":"Institute of Sport Science and Innovations Lithuanian Sports University  Kaunas Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9522-6050","authenticated-orcid":false,"given":"Petras","family":"Minderis","sequence":"additional","affiliation":[{"name":"Institute of Sport Science and Innovations Lithuanian Sports University  Kaunas 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