{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:26:55Z","timestamp":1790864815759,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG057734"],"award-info":[{"award-number":["AG057734"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mice with disruptions of growth hormone\u2010releasing hormone (GHRH) or growth hormone receptor (GHR) exhibit similar phenotypes of prolonged lifespan and delayed age\u2010related diseases. However, these two models respond differently to calorie restriction indicating that they might carry different and\/or independent mechanisms for improved longevity and healthspan. In order to elucidate these mechanisms, we generated GHRH and GHR double\u2010knockout mice (D\u2010KO). In the present study, we focused specifically on the characteristics of female D\u2010KO mice. The D\u2010KO mice have reduced body weight and enhanced insulin sensitivity compared to wild\u2010type (WT) controls. Growth retardation in D\u2010KO mice is accompanied by decreased GH expression in pituitary, decreased circulating IGF\u20101, increased high\u2010molecular\u2010weight (HMW) adiponectin, and leptin hormones compared to WT controls. Generalized linear model\u2010based regression analysis, which controls for body weight differences between D\u2010KO and WT groups, shows that D\u2010KO mice have decreased lean mass, bone mineral density, and bone mineral content, but increased adiposity. Indirect calorimetry markers including oxygen consumption, carbon dioxide production, and energy expenditure were significantly lower in D\u2010KO mice relative to the controls. In comparison with WT mice, the D\u2010KO mice displayed reduced respiratory exchange ratio (RER) values only during the light cycle, suggesting a circadian\u2010related metabolic shift toward fat utilization. Interestingly, to date survival data suggest extended lifespan in D\u2010KO female mice.<\/jats:p>","DOI":"10.1111\/acel.13339","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T12:44:50Z","timestamp":1616503490000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Physiological and metabolic characteristics of novel double\u2010mutant female mice with targeted disruption of both growth hormone\u2010releasing hormone and growth hormone receptor"],"prefix":"10.1111","volume":"20","author":[{"given":"Mert","family":"Icyuz","sequence":"first","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Fitch","sequence":"additional","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Joyner","sequence":"additional","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil K.","family":"Challa","sequence":"additional","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9802-6780","authenticated-orcid":false,"given":"Liou Y.","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham  Birmingham Alabama 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