{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:46:46Z","timestamp":1792482406840,"version":"4.5.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200945"],"award-info":[{"award-number":["82200945"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2020MH021"],"award-info":[{"award-number":["ZR2020MH021"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sarcopenia, a degenerative condition marked by progressive skeletal muscle atrophy and impaired regeneration, is closely associated with aging, chronic inflammation, and disrupted proteostasis. While macroautophagy has been extensively studied in this context, little of the role of chaperone-mediated autophagy (CMA) has been known. In this study, we identified C1q\/TNF-related protein 9 (CTRP9) as a novel autocrine myokine secreted by skeletal muscle that exerts dual protective functions\u2014pro-differentiative and anti-atrophic. By using a replicative senescence model in C2C12 myoblasts, we observed that CTRP9 expression declined with cellular aging, accompanied by reduced levels of lysosome-associated membrane protein type 2A (LAMP2A), increased nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) accumulation, and elevated interleukin-1\u03b2 (IL-1\u03b2) secretion. Similar molecular signatures were detected in skeletal muscle tissues of CTRP9 knockout (KO) mice, further validating its role in vivo. Treatment with the biologically active globular domain of CTRP9 (gCTRP9) restored LAMP2A expression, enhanced CMA activity, and promoted selective degradation of NLRP3, thereby alleviating inflammatory stress and cellular senescence. Functionally, gCTRP9 restored myogenic differentiation markers (e.g., MYOD1) while suppressing atrophy-related genes (e.g., Fbxo32) and improving fusion potential and myotube integrity. In primary human myoblasts isolated from elderly individuals, CTRP9 and LAMP2A were significantly downregulated, and NLRP3 expression was increased\u2014changes that were partially reversed upon gCTRP9 treatment. These findings collectively demonstrate that the CTRP9\u2013LAMP2A\u2013NLRP3 axis plays a pivotal role in regulating both muscle regeneration and maintenance. By targeting CMA-mediated NLRP3 degradation, CTRP9 offers a promising therapeutic strategy for combating sarcopenia through coordinated modulation of differentiation pathways and muscle atrophy.<\/jats:p>","DOI":"10.1038\/s41419-025-08025-w","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T08:29:53Z","timestamp":1759825793000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["CTRP9 as a myokine mitigates sarcopenia via the LAMP-2A\/NLRP3 pathway"],"prefix":"10.1038","volume":"16","author":[{"given":"Linxi","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangqiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaomeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyun","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyan","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2233-4063","authenticated-orcid":false,"given":"Tingting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4178-369X","authenticated-orcid":false,"given":"Yuan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"8025_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101200","volume":"65","author":"P Wiedmer","year":"2021","unstructured":"Wiedmer P, Jung T, Castro JP, Pomatto LCD, Sun PY, Davies KJA, et al. Sarcopenia - molecular mechanisms and open questions. Ageing Res Rev. 2021;65:101200.","journal-title":"Ageing Res Rev"},{"key":"8025_CR2","doi-asserted-by":"crossref","unstructured":"Cruz-Jentoft AJ, Sayer AA. Sarcopenia. Lancet. 2019;393:2636-46.","DOI":"10.1016\/S0140-6736(19)31138-9"},{"key":"8025_CR3","doi-asserted-by":"publisher","DOI":"10.1186\/2049-3258-72-45","volume":"72","author":"C Beaudart","year":"2014","unstructured":"Beaudart C, Rizzoli R, Bruy\u00e8re O, Reginster J-Y, Biver E. Sarcopenia: burden and challenges for public health. Arch Public Health. 2014;72:45.","journal-title":"Arch Public Health"},{"key":"8025_CR4","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","volume":"186","author":"C L\u00f3pez-Ot\u00edn","year":"2023","unstructured":"L\u00f3pez-Ot\u00edn C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186:243\u201378.","journal-title":"Cell"},{"key":"8025_CR5","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.ymeth.2015.01.003","volume":"75","author":"B Patel","year":"2015","unstructured":"Patel B, Cuervo AM. Methods to study chaperone-mediated autophagy. Methods. 2015;75:133\u201340.","journal-title":"Methods"},{"key":"8025_CR6","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1126\/science.273.5274.501","volume":"273","author":"AM Cuervo","year":"1996","unstructured":"Cuervo AM, Dice JF. A receptor for the selective uptake and degradation of proteins by lysosomes. Science. 1996;273:501\u20133.","journal-title":"Science"},{"key":"8025_CR7","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/s41580-018-0001-6","volume":"19","author":"S Kaushik","year":"2018","unstructured":"Kaushik S, Cuervo AM. The coming of age of chaperone-mediated autophagy. Nat Rev Mol Cell Biol. 2018;19:365\u201381.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"8025_CR8","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.arr.2017.11.001","volume":"41","author":"D Moreno-Blas","year":"2018","unstructured":"Moreno-Blas D, Gorostieta-Salas E, Castro-Obreg\u00f3n S. Connecting chaperone-mediated autophagy dysfunction to cellular senescence. Ageing Res Rev. 2018;41:34\u201341.","journal-title":"Ageing Res Rev"},{"key":"8025_CR9","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s40478-014-0182-y","volume":"3","author":"M Rothaug","year":"2015","unstructured":"Rothaug M, Stroobants S, Schweizer M, Peters J, Zunke F, Allerding M, et al. LAMP-2 deficiency leads to hippocampal dysfunction but normal clearance of neuronal substrates of chaperone-mediated autophagy in a mouse model for Danon disease. Acta Neuropathol Commun. 2015;3:6.","journal-title":"Acta Neuropathol Commun"},{"key":"8025_CR10","doi-asserted-by":"publisher","first-page":"2230","DOI":"10.1080\/15548627.2016.1214777","volume":"12","author":"M Xilouri","year":"2016","unstructured":"Xilouri M, Brekk OR, Polissidis A, Chrysanthou-Piterou M, Kloukina I, Stefanis L. Impairment of chaperone-mediated autophagy induces dopaminergic neurodegeneration in rats. Autophagy. 2016;12:2230\u201347.","journal-title":"Autophagy"},{"key":"8025_CR11","doi-asserted-by":"publisher","first-page":"583","DOI":"10.18632\/aging.101181","volume":"9","author":"J Zhou","year":"2017","unstructured":"Zhou J, Chong SY, Lim A, Singh BK, Sinha RA, Salmon AB, et al. Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging. Aging. 2017;9:583\u201399.","journal-title":"Aging"},{"key":"8025_CR12","first-page":"4685","volume":"15","author":"KK Zhang","year":"2023","unstructured":"Zhang KK, Zhang P, Kodur A, Erturk I, Burns CM, Kenyon C, et al. LAMP2A, and other chaperone-mediated autophagy related proteins, do not decline with age in genetically heterogeneous UM-HET3 mice. Aging. 2023;15:4685\u201398.","journal-title":"Aging"},{"key":"8025_CR13","doi-asserted-by":"crossref","unstructured":"Sayed RK, Fern\u00e1ndez-Ortiz M, Fern\u00e1ndez-Mart\u00ednez J, Aranda Mart\u00ednez P, Guerra-Librero A, Rodr\u00edguez-Santana C, et al. The impact of melatonin and NLRP3 inflammasome on the expression of microRNAs in AGED MUscle. Antioxidants. 2021;10:524.","DOI":"10.3390\/antiox10040524"},{"key":"8025_CR14","doi-asserted-by":"crossref","unstructured":"De Biase D, Piegari G, Prisco F, Cimmino I, d\u2019Aquino I, Baldassarre V, et al. Implication of the NLRP3 inflammasome in bovine age-related sarcopenia. Int J Mol Sci. 2021;22:3609.","DOI":"10.3390\/ijms22073609"},{"key":"8025_CR15","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02349-y","volume":"18","author":"J Chen","year":"2021","unstructured":"Chen J, Mao K, Yu H, Wen Y, She H, Zhang H, et al. p38-TFEB pathways promote microglia activation through inhibiting CMA-mediated NLRP3 degradation in Parkinson\u2019s disease. J Neuroinflam. 2021;18:295.","journal-title":"J Neuroinflam"},{"key":"8025_CR16","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1161\/CIRCRESAHA.121.318908","volume":"129","author":"L Qiao","year":"2021","unstructured":"Qiao L, Ma J, Zhang Z, Sui W, Zhai C, Xu D, et al. Deficient chaperone-mediated autophagy promotes inflammation and atherosclerosis. Circ Res. 2021;129:1141\u201357.","journal-title":"Circ Res"},{"key":"8025_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2020.109094","volume":"329","author":"A Zuo","year":"2020","unstructured":"Zuo A, Li J, Zhao X, Li T, Lei S, Chen J, et al. Globular CTRP9 protects cardiomyocytes from palmitic acid-induced oxidative stress by enhancing autophagic flux. Chem Biol Interact. 2020;329:109094.","journal-title":"Chem Biol Interact"},{"key":"8025_CR18","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1407883","volume":"15","author":"S Ruan","year":"2024","unstructured":"Ruan S, Li J, Lei S, Zhang S, Xu D, Zuo A, et al. Knockout of C1q\/tumor necrosis factor-related protein-9 aggravates cardiac fibrosis in diabetic mice by regulating YAP-mediated autophagy. Front Pharm. 2024;15:1407883.","journal-title":"Front Pharm"},{"key":"8025_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2024.109694","volume":"131","author":"S Lei","year":"2024","unstructured":"Lei S, Li X, Zuo A, Ruan S, Guo Y. CTRP9 alleviates diet induced obesity through increasing lipolysis mediated by enhancing autophagy-initiation complex formation. J Nutr Biochem. 2024;131:109694.","journal-title":"J Nutr Biochem"},{"key":"8025_CR20","first-page":"1054","volume":"42","author":"Q Li","year":"2018","unstructured":"Li Q, Zhu Z, Wang C, Cai L, Lu J, Wang Y, et al. CTRP9 ameliorates cellular senescence via PGC\u20111\u03b1\/AMPK signaling in mesenchymal stem cells. Int J Mol Med. 2018;42:1054\u201363.","journal-title":"Int J Mol Med"},{"key":"8025_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2020.111114","volume":"521","author":"J Lee","year":"2021","unstructured":"Lee J, Yoo JH, Kim HS, Cho YK, Lee YL, Lee WJ, et al. C1q\/TNF-related protein-9 attenuates palmitic acid-induced endothelial cell senescence via increasing autophagy. Mol Cell Endocrinol. 2021;521:111114.","journal-title":"Mol Cell Endocrinol"},{"key":"8025_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109694","volume":"73","author":"A Rezabakhsh","year":"2020","unstructured":"Rezabakhsh A, Sadeghpour Y, Ghaderi S, Rahbarghazi R, Geranmayeh MH. CTRP9: An emerging potential anti-aging molecule in brain. Cell Sig. 2020;73:109694.","journal-title":"Cell Sig"},{"key":"8025_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.105934","volume":"77","author":"H Zhang","year":"2019","unstructured":"Zhang H, Gong X, Ni S, Wang Y, Zhu L, Ji N. C1q\/TNF-related protein-9 attenuates atherosclerosis through AMPK-NLRP3 inflammasome singling pathway. Int Immunopharmacol. 2019;77:105934.","journal-title":"Int Immunopharmacol"},{"key":"8025_CR24","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1002\/tox.23452","volume":"37","author":"B Wang","year":"2022","unstructured":"Wang B, Li Y, Hu S, Peng K. C1q\/tumor necrosis factor-related protein 9 protects cultured chondrocytes from IL-1\u03b2-induced inflammatory injury by inhibiting NLRP3 inflammasome activation via the AdipoR1\/AMPK axis. Environ Toxicol. 2022;37:889\u201398.","journal-title":"Environ Toxicol"},{"key":"8025_CR25","doi-asserted-by":"publisher","first-page":"3773","DOI":"10.1002\/jcb.23308","volume":"112","author":"AP Sharples","year":"2011","unstructured":"Sharples AP, Al-Shanti N, Lewis MP, Stewart CE. Reduction of myoblast differentiation following multiple population doublings in mouse C2 C12 cells: a model to investigate ageing?. J Cell Biochem. 2011;112:3773\u201385.","journal-title":"J Cell Biochem"},{"key":"8025_CR26","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1161\/ATVBAHA.115.305706","volume":"35","author":"J-R Lin","year":"2015","unstructured":"Lin J-R, Shen W-L, Yan C, Gao P-J. Downregulation of dynamin-related protein 1 contributes to impaired autophagic flux and angiogenic function in senescent endothelial cells. Arterioscler Thrombosis Vasc Biol. 2015;35:1413\u201322.","journal-title":"Arterioscler Thrombosis Vasc Biol"},{"key":"8025_CR27","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1016\/j.exger.2004.07.008","volume":"39","author":"P Lorenzon","year":"2004","unstructured":"Lorenzon P, Bandi E, de Guarrini F, Pietrangelo T, Sch\u00e4fer R, Zweyer M, et al. Ageing affects the differentiation potential of human myoblasts. Exp Gerontol. 2004;39:1545\u201354.","journal-title":"Exp Gerontol"},{"key":"8025_CR28","doi-asserted-by":"publisher","first-page":"3122","DOI":"10.1002\/jcsm.13100","volume":"13","author":"IS Sinam","year":"2022","unstructured":"Sinam IS, Chanda D, Thoudam T, Kim M-J, Kim B-G, Kang H-J, et al. Pyruvate dehydrogenase kinase 4 promotes ubiquitin-proteasome system-dependent muscle atrophy. J Cachexia Sarcopenia Muscle. 2022;13:3122\u201336.","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"8025_CR29","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1002\/jcsm.13166","volume":"14","author":"X Jiang","year":"2023","unstructured":"Jiang X, Ji S, Yuan F, Li T, Cui S, Wang W, et al. Pyruvate dehydrogenase B regulates myogenic differentiation via the FoxP1-Arih2 axis. J Cachexia Sarcopenia Muscle. 2023;14:606\u201321.","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"8025_CR30","doi-asserted-by":"publisher","first-page":"E222","DOI":"10.1152\/ajpendo.00060.2017","volume":"313","author":"MJ McBride","year":"2017","unstructured":"McBride MJ, Foley KP, D\u2019Souza DM, Li YE, Lau TC, Hawke TJ, et al. The NLRP3 inflammasome contributes to sarcopenia and lower muscle glycolytic potential in old mice. Am J Physiol Endocrinol Metab. 2017;313:E222\u2013E32.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"8025_CR31","doi-asserted-by":"crossref","unstructured":"Jorquera G, Russell J, Monsalves-\u00c1lvarez M, Cruz G, Valladares-Ide D, Basualto-Alarc\u00f3n C, et al. NLRP3 inflammasome: potential role in obesity related low-grade inflammation and insulin resistance in skeletal muscle. Int J Mol Sci. 2021;22:3254.","DOI":"10.3390\/ijms22063254"},{"key":"8025_CR32","doi-asserted-by":"crossref","unstructured":"Moustogiannis A, Philippou A, Taso O, Zevolis E, Pappa M, Chatzigeorgiou A, et al. The effects of muscle cell aging on myogenesis. Int J Mol Sci. 2021;22:3721.","DOI":"10.3390\/ijms22073721"},{"key":"8025_CR33","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1002\/jcsm.13228","volume":"14","author":"BY-H Wang","year":"2023","unstructured":"Wang BY-H, Chen Y-F, Hsiao AW-T, Chen W-J, Lee C-W, Lee OK-S. Ginkgolide B facilitates muscle regeneration via rejuvenating osteocalcin-mediated bone-to-muscle modulation in aged mice. J Cachexia Sarcopenia Muscle. 2023;14:1349\u201364.","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"8025_CR34","doi-asserted-by":"crossref","unstructured":"Sharpless NE. Ink4a\/Arf links senescence and aging. Exp Gerontol. 2004;39:1751\u20139.","DOI":"10.1016\/j.exger.2004.06.025"},{"key":"8025_CR35","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1002\/1097-0029(20000915)50:6<500::AID-JEMT7>3.0.CO;2-7","volume":"50","author":"D Pette","year":"2000","unstructured":"Pette D, Staron RS. Myosin isoforms, muscle fiber types, and transitions. Microsc Res Tech. 2000;50:500\u20139.","journal-title":"Microsc Res Tech"},{"key":"8025_CR36","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1002\/jcsm.13034","volume":"13","author":"AD Brown","year":"2022","unstructured":"Brown AD, Stewart CE, Burniston JG. Degradation of ribosomal and chaperone proteins is attenuated during the differentiation of replicatively aged C2C12 myoblasts. J Cachexia Sarcopenia Muscle. 2022;13:2562\u201375.","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"8025_CR37","doi-asserted-by":"publisher","first-page":"3048","DOI":"10.1002\/jcsm.13062","volume":"13","author":"M Eggelbusch","year":"2022","unstructured":"Eggelbusch M, Shi A, Broeksma BC, V\u00e1zquez-Cruz M, Soares MN, de Wit GMJ, et al. The NLRP3 inflammasome contributes to inflammation-induced morphological and metabolic alterations in skeletal muscle. J Cachexia Sarcopenia Muscle. 2022;13:3048\u201361.","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"8025_CR38","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1080\/15548627.2024.2395158","volume":"21","author":"S Yang","year":"2025","unstructured":"Yang S, Li M, Lian G, Wu Y, Cui J, Wang L. ABHD8 antagonizes inflammation by facilitating chaperone-mediated autophagy-mediated degradation of NLRP3. Autophagy. 2025;21:338\u201351.","journal-title":"Autophagy"},{"key":"8025_CR39","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.arr.2015.05.001","volume":"22","author":"A Kalinkovich","year":"2015","unstructured":"Kalinkovich A, Livshits G. Sarcopenia-The search for emerging biomarkers. Ageing Res Rev. 2015;22:58\u201371.","journal-title":"Ageing Res Rev"},{"key":"8025_CR40","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1111\/j.1474-9726.2012.00869.x","volume":"11","author":"AP Sharples","year":"2012","unstructured":"Sharples AP, Player DJ, Martin NRW, Mudera V, Stewart CE, Lewis MP. Modelling in vivo skeletal muscle ageing in vitro using three-dimensional bioengineered constructs. Aging Cell. 2012;11:986\u201395.","journal-title":"Aging Cell"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-08025-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-08025-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-08025-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T21:10:25Z","timestamp":1759871425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-08025-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,7]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8025"],"URL":"https:\/\/doi.org\/10.1038\/s41419-025-08025-w","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,7]]},"assertion":[{"value":"20 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Human sample collection and experimental procedures were approved by the Ethics Committee of Qilu Hospital of Shandong University. Specifically, Approval No. KYLL-202306(XZ)-028-1 was granted for the collection of serum samples, and Approval No. KYLL-202504-032 was granted for the acquisition of skeletal muscle biopsies. All participants provided written informed consent prior to enrollment. The study was conducted in accordance with the principles of the Declaration of Helsinki and the CIOMS (Council for International Organizations of Medical Sciences) guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"710"}}