{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:53:19Z","timestamp":1790938399455,"version":"4.1.0"},"reference-count":48,"publisher":"PAGEPress Publications","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Transl Myol"],"abstract":"<jats:p>With advancing age, cardiac weakness and a progressive loss of skeletal muscle mass and contractile strength, is observed in most humans. Although considerable inter-individual differences exist in the degree of age-related muscle wasting, progressive cardiac impairment and sarcopenia play a key role during the natural aging process and form an integral part of the frailty syndrome. Here, we have used comparative bottom-up proteomic profiling to study age-related changes in an established murine model of sarcopenia. The simultaneous assessment of heart and diaphragm muscle aging using peptide mass spectrometry showed that senescence is associated with myofiber degeneration, considerable changes in metabolic processes and increased extracellular matrix deposition. A striking reduction in two mitochondrial enzymes, NAD(P) transhydrogenase and hydroxymethylglutaryl-CoA synthase, was identified by proteomics in the senescent heart and diaphragm muscle, respectively. Bioinformatic analyses revealed abundance changes in distinct protein families and potential alterations in protein-protein interaction patterns. The altered protein profile of the heart-diaphragm system, as determined by comparative discovery proteomics, can be helpful to establish an improved biomarker signature for diagnostic, prognostic and therapeutic monitoring of muscle aging.<\/jats:p>","DOI":"10.4081\/ejtm.2026.16061","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:55:52Z","timestamp":1790934952000},"source":"Crossref","is-referenced-by-count":0,"title":["Proteomic and bioinformatic profiling of the aging mouse heart-diaphragm system&lt;b&gt;&lt;\/b&gt;"],"prefix":"10.4081","author":[{"given":"Paul","family":"Dowling","sequence":"first","affiliation":[{"name":"Department of Biology, Maynooth University, National University of Ireland, Maynooth, Co. Kildare, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5615-1869","authenticated-orcid":true,"given":"Margit","family":"Zweyer","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases, Bonn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2749-7163","authenticated-orcid":true,"given":"Felix","family":"Nebeling","sequence":"additional","affiliation":[{"name":"Department of Neurooncology, Center for Neurology, University Hospital Bonn, Bonn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Swandulla","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Medical Faculty, University of Bonn, Bonn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-4510","authenticated-orcid":true,"given":"Kay","family":"Ohlendieck","sequence":"additional","affiliation":[{"name":"Department of Biology, Maynooth University, National University of Ireland, Maynooth, Co. Kildare, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2549","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"254336","doi-asserted-by":"crossref","unstructured":"1. Sieck GC, Fogarty MJ. Diaphragm muscle: a pump that can not fail. Physiol Rev 2025;105:2589\u20132656.","DOI":"10.1152\/physrev.00043.2024"},{"key":"254337","doi-asserted-by":"crossref","unstructured":"2. Anderson RH, Razavi R, Taylor AM. Cardiac anatomy revisited. J Anat 2004;205:159\u201377.","DOI":"10.1111\/j.0021-8782.2004.00330.x"},{"key":"254338","doi-asserted-by":"crossref","unstructured":"3. Kelley RC, Ferreira LF. Diaphragm abnormalities in heart failure and aging: mechanisms and integration of cardiovascular and respiratory pathophysiology. Heart Fail Rev 2017;22:191\u2013207.","DOI":"10.1007\/s10741-016-9549-4"},{"key":"254339","doi-asserted-by":"crossref","unstructured":"4. Salah HM, Goldberg LR, Molinger J, et al. Diaphragmatic function in cardiovascular disease: JACC review topic of the week. J Am Coll Cardiol 2022;80:1647\u201359.","DOI":"10.1016\/j.jacc.2022.08.760"},{"key":"254340","doi-asserted-by":"crossref","unstructured":"5. Castro C, Delwarde C, Shi Y, Roh J. Geroscience in heart failure: the search for therapeutic targets in the shared pathobiology of human aging and heart failure. J Cardiovasc Aging 2025;5:10.20517\/jca.2024.15.","DOI":"10.20517\/jca.2024.15"},{"key":"254341","doi-asserted-by":"crossref","unstructured":"6. Sayer AA, Cooper R, Arai H, et al. Sarcopenia. Nat Rev Dis Primers 2024;10:68.","DOI":"10.1038\/s41572-024-00550-w"},{"key":"254342","doi-asserted-by":"crossref","unstructured":"7. Picca A, Coelho-Junior HJ, Calvani R, et al. 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Lifelong dietary protein restriction accelerates skeletal muscle loss and reduces muscle fibre size by impairing proteostasis and mitochondrial homeostasis. Redox Biol 2024;69:102980.","DOI":"10.1016\/j.redox.2023.102980"},{"key":"254357","doi-asserted-by":"crossref","unstructured":"22. Soffe Z, Radley-Crabb HG, McMahon C, et al. Effects of loaded voluntary wheel exercise on performance and muscle hypertrophy in young and old male C57Bl\/6J mice. Scand J Med Sci Sports 2016;26:172\u201388.","DOI":"10.1111\/sms.12416"},{"key":"254358","doi-asserted-by":"crossref","unstructured":"23. Dowling P, Gargan S, Zweyer M, et al. Proteomic reference map for sarcopenia research: mass spectrometric identification of key muscle proteins located in the sarcomere, cytoskeleton and the extracellular matrix. Eur J Transl Myol 2024;34:12564.","DOI":"10.4081\/ejtm.2024.12564"},{"key":"254359","doi-asserted-by":"crossref","unstructured":"24. Gargan S, Dowling P, Zweyer M, et al. Proteomic identification of markers of membrane repair, regeneration and fibrosis in the aged and dystrophic diaphragm. Life (Basel) 2022;12:1679.","DOI":"10.3390\/life12111679"},{"key":"254360","doi-asserted-by":"crossref","unstructured":"25. Murphy S, Zweyer M, Henry M, et al. Proteomic analysis of the sarcolemma-enriched fraction from dystrophic mdx-4cv skeletal muscle. J Proteomics 2019;191:212\u201327.","DOI":"10.1016\/j.jprot.2018.01.015"},{"key":"254361","doi-asserted-by":"crossref","unstructured":"26. Dowling P, Gargan S, Zweyer M, et al. Protocol for the bottom-up proteomic analysis of mouse spleen. STAR Protoc 2020;1:100196.","DOI":"10.1016\/j.xpro.2020.100196"},{"key":"254362","doi-asserted-by":"crossref","unstructured":"27. Dowling P, Gargan S, Zweyer M, et al. Proteomic reference map for sarcopenia research: mass spectrometric identification of key muscle proteins of organelles, cellular signaling, bioenergetic metabolism and molecular chaperoning. 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Deciphering the transcriptomic signatures of aging across organs in mice. Aging Cell 2026;25:e70357.","DOI":"10.1111\/acel.70357"},{"key":"254383","doi-asserted-by":"crossref","unstructured":"48. Wang Q, Xu Z, Ding X, et al. Ten mouse organs proteome and metabolome atlas from adult to aging. Genome Med 2025;17:116.","DOI":"10.1186\/s13073-025-01535-4"}],"container-title":["European Journal of Translational Myology"],"original-title":[],"link":[{"URL":"https:\/\/www.pagepressjournals.org\/bam\/article\/download\/16061\/14540","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.pagepressjournals.org\/bam\/article\/download\/16061\/14540","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:56:01Z","timestamp":1790934961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.pagepressjournals.org\/bam\/article\/view\/16061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,2]]},"references-count":48,"URL":"https:\/\/doi.org\/10.4081\/ejtm.2026.16061","relation":{},"ISSN":["2037-7460","2037-7452"],"issn-type":[{"value":"2037-7460","type":"electronic"},{"value":"2037-7452","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10,2]]}}}