{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:53:54Z","timestamp":1793051634845,"version":"4.5.0"},"reference-count":64,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Aging is associated with a progressive reduction in cellular function leading to poor health and loss of physical performance. Mitochondrial dysfunction is one of the hallmarks of aging; hence, interventions targeting mitochondrial dysfunction have the potential to provide preventive and therapeutic benefits to elderly individuals. Meta\u2010analyses of age\u2010related gene expression profiles showed that the expression of Ahnak1, a protein regulating several signal\u2010transduction pathways including metabolic homeostasis, is increased with age, which is associated with low VO\n                      <jats:sub>2MAX<\/jats:sub>\n                      and poor muscle fitness. However, the role of Ahnak1 in the aging process remained unknown. Here, we investigated the age\u2010related role of Ahnak1 in murine exercise capacity, mitochondrial function, and contractile function of cardiac and skeletal muscles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed 15\u2010 to 16\u2010month\u2010old female and male Ahnak1\u2010knockout (Ahnak1\u2010KO) and wild\u2010type (WT) mice and performed morphometric, biochemical, and bioenergetics assays to evaluate the effects of Ahnak1 on exercise capacity and mitochondrial morphology and function in cardiomyocytes and tibialis anterior (TA) muscle. A human left ventricular (LV) cardiomyocyte cell line (AC16) was used to investigate the direct role of Ahnak1 in cardiomyocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that the level of Ahnak1 protein is significantly up\u2010regulated with age in the murine LV (1.9\u2010fold) and TA (1.8\u2010fold) tissues. The suppression of Ahnak1 was associated with improved exercise tolerance, as all aged adult Ahnak1\u2010KO mice (100%) successfully completed the running programme, whereas approximately 31% male and 8% female WT mice could maintain the required running speed and distance. Transmission electron microscopic studies showed that LV and TA tissue specimens of aged adult Ahnak1\u2010KO of both sexes have significantly more enlarged\/elongated mitochondria and less small mitochondria compared with WT littermates (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01 and\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001, respectively) at basal level. Further, we observed a shift in mitochondrial fission\/fusion balance towards fusion in cardiomyocytes and TA muscle from aged adult Ahnak1\u2010KO mice. The maximal and reserve respiratory capacities were significantly higher in cardiomyocytes from aged adult Ahnak1\u2010KO mice compared with the WT counterparts (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05 and\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01, respectively). Cardiomyocyte contractility and fatigue resistance of TA muscles were significantly increased in Ahnak1\u2010KO mice of both sexes, compared with the WT groups.\n                      <jats:italic>In vitro<\/jats:italic>\n                      studies using AC16 cells have confirmed that the alteration of mitochondrial function is indeed a direct effect of Ahnak1. Finally, we presented Ahnak1 as a novel cardiac mitochondrial membrane\u2010associated protein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data suggest that Ahnak1 is involved in age\u2010related cardiac and skeletal muscle dysfunction and could therefore serve as a promising therapeutical target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12749","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T05:40:06Z","timestamp":1625204406000},"page":"1249-1265","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Age\u2010related decline in murine heart and skeletal muscle performance is attenuated by reduced Ahnak1 expression"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3094-7874","authenticated-orcid":false,"given":"Shokoufeh","family":"Mahmoodzadeh","sequence":"first","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine in the Helmholtz Association (MDC)  Berlin Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Koch","sequence":"additional","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine in the Helmholtz Association (MDC)  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Schriever","sequence":"additional","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine in the Helmholtz Association (MDC)  Berlin 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