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The Growth Hormone Receptor Knockout (GHR-KO) mouse, a model of GH insensitivity, characterized by chronically elevated circulating GH, provides a unique opportunity to examine the consequences of disrupted GH signaling during aging. Given the close relationship between circadian rhythmicity and GH secretion, we investigated sex- and genotype-specific differences in circadian activity, neuromuscular, and neurocognitive performance in aged GHR-KO mice under varying light\u2013dark (LD), constant dark (DD) conditions, and subsequently examined the impact of circadian disruption (CD) on these parameters. Female GHR-wildtype (fGHR-WT) mice showed greater overall total activity, enhanced circadian activity amplitude, and less fragmented rhythms compared to female GHR-knockout (fGHR-KO) mice. In contrast, fGHR-KO mice demonstrated more rapid re-entrainment following phase shifts, indicating differences in circadian adaptation. Both fGHR-WT and fGHR-KO mice exhibited superior working memory compared to male littermates, while GHR-KO mice displayed enhanced neuromuscular performance compared with GHR-WT controls. CD reduced rhythm stability and was associated with declines in neuromuscular and cognitive performance, particularly in females, as well as increased open field (OF) immobility in fGHR-KO. Collectively, these findings indicate that aged GHR-WT and GHR-KO mice exhibit distinct circadian and behavioral phenotypes, and that disruption of circadian organization exacerbates cognitive and neuromuscular vulnerability.<\/jats:p>","DOI":"10.1007\/s11357-026-02479-2","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T19:31:35Z","timestamp":1786563095000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-specific circadian and behavioral phenotypes in aged growth hormone receptor knockout mice"],"prefix":"10.1007","author":[{"given":"Sean M.","family":"Hicks","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8016-6398","authenticated-orcid":false,"given":"Shelley A.","family":"Tischkau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"2479_CR1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.4137\/CMED.S38201","volume":"9","author":"J Devesa","year":"2016","unstructured":"Devesa J, Almengl\u00f3 C, Devesa P. 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