{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:20:50Z","timestamp":1791951650475,"version":"4.3.4"},"reference-count":68,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Epigenes Australia","award":["CPQ-2618253"],"award-info":[{"award-number":["CPQ-2618253"]}]},{"name":"Oracle for Research","award":["CPQ-2618253"],"award-info":[{"award-number":["CPQ-2618253"]}]},{"name":"Nectar Research Cloud","award":["CPQ-2618253"],"award-info":[{"award-number":["CPQ-2618253"]}]},{"name":"Pawsey Supercomputing Centre","award":["CPQ-2618253"],"award-info":[{"award-number":["CPQ-2618253"]}]},{"name":"Government of Western Australia","award":["CPQ-2618253"],"award-info":[{"award-number":["CPQ-2618253"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Further examination of the molecular regulators of long-term calorie restriction (CR), reported to have an anxiolytic effect, may highlight novel therapeutic targets for anxiety disorders. Here, adult male Hooded Wistar rats were exposed to a 25% CR whilst anxiety-like behaviour was assessed at 6-, 12-, and 18-months of age via the elevated plus maze, open field, and acoustic startle tests. Next-generation sequencing was then used to measure transcriptome-wide gene expression in the hypothalamus, amygdala, pituitary, and adrenal glands. Results showed an anxiolytic behavioural profile across early, middle, and late adulthood by CR, with the strongest effects noted at 6-months. Transcriptomic analysis by seven attribute weighting algorithms, including Info Gain Ratio, Rule, Chi Squared, Gini Index, Uncertainty, Relief, and Info Gain, led to the development of a signature of long-term CR, independent of region. Complement C1q A chain (C1qa), an extracellular protein, expression was significantly decreased by CR in most regions examined. Furthermore, text mining highlighted the positive involvement of C1qa in anxiety, depression, neurodegeneration, stress, and ageing, collectively identifying a suitable biomarker candidate for CR. Overall, the current study identified anxiety-related phenotypic changes and a novel transcriptome signature of long-term CR, indicating potential therapeutic targets for anxiety, depression, and neurodegeneration.<\/jats:p>","DOI":"10.3390\/nu14214670","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T09:23:37Z","timestamp":1667553817000},"page":"4670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Long-Term Calorie Restriction Alters Anxiety-like Behaviour and the Brain and Adrenal Gland Transcriptomes of the Ageing Male Rat"],"prefix":"10.3390","volume":"14","author":[{"given":"Antonina","family":"Govic","sequence":"first","affiliation":[{"name":"School of Psychology and Public Health, La Trobe University, Melbourne, VIC 3010, Australia"},{"name":"Epigenes Australia Pty Ltd., Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4021-3636","authenticated-orcid":false,"given":"Helen","family":"Nasser","sequence":"additional","affiliation":[{"name":"School of Psychology and Public Health, La Trobe University, Melbourne, VIC 3010, Australia"},{"name":"Epigenes Australia Pty Ltd., Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Levay","sequence":"additional","affiliation":[{"name":"School of Psychology and Public Health, La Trobe University, Melbourne, VIC 3010, Australia"},{"name":"Epigenes Australia Pty Ltd., Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2023-6489","authenticated-orcid":false,"given":"Matt","family":"Zelko","sequence":"additional","affiliation":[{"name":"School of Psychology and Public Health, La Trobe University, Melbourne, VIC 3010, Australia"},{"name":"Epigenes Australia Pty Ltd., Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4431-2861","authenticated-orcid":false,"given":"Esmaeil","family":"Ebrahimie","sequence":"additional","affiliation":[{"name":"Genomics Research Platform, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC 3000, Australia"},{"name":"School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, SA 5371, Australia"},{"name":"School of BioSciences, The University of Melbourne, Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manijeh","family":"Mohammadi Dehcheshmeh","sequence":"additional","affiliation":[{"name":"Genomics Research Platform, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC 3000, Australia"},{"name":"School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, SA 5371, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Kent","sequence":"additional","affiliation":[{"name":"School of Psychology and Public Health, La Trobe University, Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Penman","sequence":"additional","affiliation":[{"name":"Epigenes Australia Pty Ltd., Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Hazi","sequence":"additional","affiliation":[{"name":"School of Psychology and Public Health, La Trobe University, Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1017\/S1041610209009399","article-title":"Depression and anxiety in medically unwell older adults: Prevalence and short-term course","volume":"21","author":"Bryant","year":"2009","journal-title":"Int. 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