{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:50:59Z","timestamp":1780098659188,"version":"3.54.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,7,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The activation of AT2 (angiotensin II type 2 receptor ) and Mas receptor by angiotensin II and angiotensin\u2010(1\u20107), respectively, is the primary process that counteracts activation of the canonical renin\u2010angiotensin system (RAS). Although inhibition of canonical RAS could delay the progression of physiological aging, we recently reported that deletion of Mas had no impact on the aging process in mice. Here, we used male mice with a deletion of only AT2 or a double deletion of AT2 and Mas to clarify whether these receptors contribute to the aging process in a complementary manner, primarily by focusing on aging\u2010related muscle weakness.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Serial changes in grip strength of these mice up to 24\u00a0months of age showed that AT2\/Mas knockout mice, but not AT2 knockout mice, had significantly weaker grip strength than wild\u2010type mice from the age of 18\u00a0months. AT2\/Mas knockout mice exhibited larger sizes, but smaller numbers and increased frequency of central nucleation (a marker of aged muscle) of single skeletal muscle fibers than AT2 knockout mice. Canonical RAS\u2010associated genes, inflammation\u2010associated genes, and senescence\u2010associated genes were highly expressed in skeletal muscles of AT2\/Mas knockout mice. Muscle angiotensin II content increased in AT2\/Mas knockout mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Double deletion of AT2 and Mas in mice exaggerated aging\u2010associated muscle weakness, accompanied by signatures of activated RAS, inflammation, and aging in skeletal muscles. Because aging\u2010associated phenotypes were absent in single deletions of the receptors, AT2 and Mas could complement each other in preventing local activation of RAS during aging.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.021030","type":"journal-article","created":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T13:07:24Z","timestamp":1625317644000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Double Deletion of Angiotensin II Type 2 and Mas Receptors Accelerates Aging\u2010Related Muscle Weakness in Male Mice"],"prefix":"10.1161","volume":"10","author":[{"given":"Hikari","family":"Takeshita","sequence":"first","affiliation":[{"name":"Department of Geriatric and General Medicine Osaka University Graduate School of Medicine Suita 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