{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:07:30Z","timestamp":1790856450118,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"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":[[2025,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Ageing is an irreversible process involving the gradual decline of cellular functions in all tissues. In male mice, age\u2010related loss of muscle force is accompanied by the formation of tubular aggregates, which are honeycomb\u2010like structures composed of membrane tubules, proteins and Ca\n 2+<\/jats:sup>\n deposits. Tubular aggregates are also found in tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK), two clinically overlapping human disorders affecting skeletal muscle, bones, skin, spleen and platelets. TAM\/STRMK is caused by gain\u2010of\u2010function mutations in the ubiquitously expressed Ca\n 2+<\/jats:sup>\n sensor STIM1 and results in excessive extracellular Ca\n 2+<\/jats:sup>\n entry and the dysregulation of Ca\n 2+<\/jats:sup>\n homeostasis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n To understand the correlation between ageing, tubular aggregate formation, Ca\n 2+<\/jats:sup>\n and STIM1, we conducted comparative analyses of WT and\n Stim1<\/jats:italic>\n \n +\/\u2212<\/jats:italic>\n <\/jats:sup>\n male mice until 18 months of age. We examined growth, general and specific muscle force, fatigability and muscle structure.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Stim1<\/jats:italic>\n \n +\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice were born with the expected Mendelian ratio and showed unremarkable postnatal development with normal body and organ weight. However, at 18 months,\n Stim1<\/jats:italic>\n \n +\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice manifested delayed muscle contraction (\n \u0394<\/jats:italic>\n \u2009=\u200928%,\n p<\/jats:italic>\n \u2009<\u20090.05) and relaxation (\n \u0394<\/jats:italic>\n \u2009=\u200940%,\n p<\/jats:italic>\n \u2009<\u20090.01) kinetics as well as exacerbated fatigue (\n \u0394<\/jats:italic>\n \u2009=\u200928%,\n p<\/jats:italic>\n \u2009<\u20090.05) compared with age\u2010matched controls. Morphological investigations of\n Stim1<\/jats:italic>\n \n +\/\u2212<\/jats:italic>\n <\/jats:sup>\n muscle sections by light and electron microscopy uncovered a shift towards slow myofibres and mitochondrial proliferation accompanied by enhanced SDH activity (\n \u0394<\/jats:italic>\n \u2009=\u200927%,\n p<\/jats:italic>\n \u2009<\u20090.0001), an almost twofold increase in ROS production (\n p<\/jats:italic>\n \u2009<\u20090.05), and signs of mitophagy\u2014all representing histopathological hallmarks of age\u2010related deterioration of muscle function known as sarcopenia. Strikingly, tubular aggregates\u2014though abundant in WT muscles at 18 months\u2014were absent in\n Stim1<\/jats:italic>\n \n +\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Taken together, STIM1 depletion by 50% had no discernible effect on muscle function in young adult male mice, but compromised muscle performance and resistance to fatigue at later life stages. These findings highlight a critical role of STIM1 and Ca\n 2+<\/jats:sup>\n balance in the maintenance of muscle physiology, fibre type composition and mitochondrial bioenergetics. The absence of tubular aggregates in\n Stim1<\/jats:italic>\n \n +\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice indicates that tubular aggregates possibly play a protective role and may contribute to the prevention of age\u2010related muscle alterations.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70151","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T01:00:23Z","timestamp":1765155623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["STIM1 Reduction Prevents Tubular Aggregate Formation and Compromises Muscle Performance in Ageing Mice"],"prefix":"10.1002","volume":"16","author":[{"given":"Laura","family":"P\u00e9rez\u2010Gu\u00e0rdia","sequence":"first","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), INSERM U1258, CNRS UMR7104 University of Strasbourg Illkirch France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0349-4283","authenticated-orcid":false,"given":"Roberto","family":"Silva\u2010Rojas","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), INSERM U1258, CNRS UMR7104 University of Strasbourg Illkirch France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"Laporte","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), INSERM U1258, CNRS UMR7104 University of Strasbourg Illkirch France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-9504","authenticated-orcid":false,"given":"Johann","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), INSERM U1258, CNRS UMR7104 University of Strasbourg Illkirch France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2018.07.008"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23899"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2018.10.004"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.08.006"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.12.007"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu477"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1312520111"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10071730"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1832"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102014\u2010102623"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2003.11.007"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2011.12.006"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004180000211"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010011\u20109211\u2010y"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.07.012"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.10.021"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200604166"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1574"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201012157"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlw096"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103044"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12938"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900082"},{"key":"e_1_2_10_25_1","first-page":"467","article-title":"The Distribution and Relative Sized of Fibre Types in the Extensor Digitorum Longus and Soleus Muscles of the Adult rat","volume":"123","author":"Pullen A. 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