{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:26:25Z","timestamp":1793834785469,"version":"4.6.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Guangdong Science and Technology Program","award":["2024B1111130001"],"award-info":[{"award-number":["2024B1111130001"]}]},{"name":"Shenzhen Science and Technology Program","award":["KJZD20240903102703005"],"award-info":[{"award-number":["KJZD20240903102703005"]}]},{"name":"Shenzhen Science and Technology Program","award":["JCYJ20240813094515020"],"award-info":[{"award-number":["JCYJ20240813094515020"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biogerontology"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1007\/s10522-026-10518-w","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:49:43Z","timestamp":1791272983000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-stratified immune patterns across the canine lifespan and short-term responses to geroprotective interventions"],"prefix":"10.1007","volume":"27","author":[{"given":"Meiling","family":"Lai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengge","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxia","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Mironenkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengxiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baichuan","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Kang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6751-5250","authenticated-orcid":false,"given":"Yu-Xuan","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"10518_CR1","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1093\/gerona\/glx182","volume":"73","author":"JE Alexander","year":"2018","unstructured":"Alexander JE, Colyer A, Haydock RM, Hayek MG, Park J (2018) Understanding how dogs age: longitudinal analysis of markers of inflammation, immune function, and oxidative stress. J Gerontol A Biol Sci Med Sci 73:720\u2013728. https:\/\/doi.org\/10.1093\/gerona\/glx182","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10518_CR2","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.cmet.2016.05.019","volume":"23","author":"SN Austad","year":"2016","unstructured":"Austad SN, Fischer KE (2016) Sex differences in lifespan. Cell Metab 23:1022\u20131033. https:\/\/doi.org\/10.1016\/j.cmet.2016.05.019","journal-title":"Cell Metab"},{"key":"10518_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2023.1168711","volume":"10","author":"BG Barnett","year":"2023","unstructured":"Barnett BG et al (2023) A masked, placebo-controlled, randomized clinical trial evaluating safety and the effect on cardiac function of low-dose rapamycin in 17 healthy client-owned dogs. Front Vet Sci 10:1168711. https:\/\/doi.org\/10.3389\/fvets.2023.1168711","journal-title":"Front Vet Sci"},{"key":"10518_CR4","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1007\/s11357-024-01484-7","volume":"47","author":"AE Coleman","year":"2025","unstructured":"Coleman AE et al (2025) Test of rapamycin in aging dogs (TRIAD): study design and rationale for a prospective, parallel-group, double-masked, randomized, placebo-controlled, multicenter trial of rapamycin in healthy middle-aged dogs from the dog aging project. Geroscience 47:2851\u20132877. https:\/\/doi.org\/10.1007\/s11357-024-01484-7","journal-title":"Geroscience"},{"key":"10518_CR5","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41586-021-04282-9","volume":"602","author":"KE Creevy","year":"2022","unstructured":"Creevy KE et al (2022) An open science study of ageing in companion dogs. Nature 602:51\u201357. https:\/\/doi.org\/10.1038\/s41586-021-04282-9","journal-title":"Nature"},{"key":"10518_CR6","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","volume":"15","author":"L Ferrucci","year":"2018","unstructured":"Ferrucci L, Fabbri E (2018) Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol 15:505\u2013522. https:\/\/doi.org\/10.1038\/s41569-018-0064-2","journal-title":"Nat Rev Cardiol"},{"key":"10518_CR7","doi-asserted-by":"publisher","first-page":"21814","DOI":"10.18632\/aging.203600","volume":"13","author":"DI Fleyshman","year":"2021","unstructured":"Fleyshman DI et al (2021) Development of infrastructure for a systemic multidisciplinary approach to study aging in retired sled dogs. Aging (Albany NY) 13:21814\u201321837. https:\/\/doi.org\/10.18632\/aging.203600","journal-title":"Aging (Albany NY)"},{"key":"10518_CR8","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","volume":"14","author":"C Franceschi","year":"2018","unstructured":"Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A (2018) Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol 14:576\u2013590. https:\/\/doi.org\/10.1038\/s41574-018-0059-4","journal-title":"Nat Rev Endocrinol"},{"key":"10518_CR9","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","volume":"908","author":"C Franceschi","year":"2000","unstructured":"Franceschi C et al (2000) Inflamm-aging: an evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244\u2013254. https:\/\/doi.org\/10.1111\/j.1749-6632.2000.tb06651.x","journal-title":"Ann N Y Acad Sci"},{"key":"10518_CR10","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.cellimm.2015.02.002","volume":"294","author":"MR Gubbels Bupp","year":"2015","unstructured":"Gubbels Bupp MR (2015) Sex, the aging immune system, and chronic disease. Cell Immunol 294:102\u2013110. https:\/\/doi.org\/10.1016\/j.cellimm.2015.02.002","journal-title":"Cell Immunol"},{"key":"10518_CR11","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63425","volume":"10","author":"S H\u00e4gg","year":"2021","unstructured":"H\u00e4gg S, Jylh\u00e4v\u00e4 J (2021) Sex differences in biological aging with a focus on human studies. Elife 10:e63425. https:\/\/doi.org\/10.7554\/eLife.63425","journal-title":"Elife"},{"key":"10518_CR12","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/nature08221","volume":"460","author":"DE Harrison","year":"2009","unstructured":"Harrison DE et al (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392\u2013395. https:\/\/doi.org\/10.1038\/nature08221","journal-title":"Nature"},{"key":"10518_CR13","doi-asserted-by":"publisher","first-page":"388","DOI":"10.3389\/fvets.2020.00388","volume":"7","author":"BL Hart","year":"2020","unstructured":"Hart BL, Hart LA, Thigpen AP, Willits NH (2020) Assisting decision-making on age of neutering for 35 breeds of dogs: associated joint disorders, cancers, and urinary incontinence. Front Vet Sci 7:388. https:\/\/doi.org\/10.3389\/fvets.2020.00388","journal-title":"Front Vet Sci"},{"key":"10518_CR14","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s11357-024-01352-4","volume":"47","author":"S Herzig","year":"2025","unstructured":"Herzig S et al (2025) A biological age based on common clinical markers predicts health trajectory and mortality risk in dogs. Geroscience 47:45\u201359. https:\/\/doi.org\/10.1007\/s11357-024-01352-4","journal-title":"Geroscience"},{"key":"10518_CR15","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12737","volume":"17","author":"JM Hoffman","year":"2018","unstructured":"Hoffman JM, Creevy KE, Franks A, O\u2019Neill DG, Promislow DEL (2018) The companion dog as a model for human aging and mortality. Aging Cell 17:e12737. https:\/\/doi.org\/10.1111\/acel.12737","journal-title":"Aging Cell"},{"key":"10518_CR16","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13653","volume":"21","author":"HSM Jayarathne","year":"2022","unstructured":"Jayarathne HSM et al (2022) Neuroprotective effects of canagliflozin: lessons from aged genetically diverse UM-HET3 mice. Aging Cell 21:e13653. https:\/\/doi.org\/10.1111\/acel.13653","journal-title":"Aging Cell"},{"key":"10518_CR17","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1007\/s10522-023-10037-y","volume":"24","author":"AG Jim\u00e9nez","year":"2023","unstructured":"Jim\u00e9nez AG (2023) Inflammaging in domestic dogs: basal level concentrations of IL-6, IL-1\u03b2, and TNF-\u03b1 in serum of healthy dogs of different body sizes and ages. Biogerontology 24:593\u2013602. https:\/\/doi.org\/10.1007\/s10522-023-10037-y","journal-title":"Biogerontology"},{"key":"10518_CR18","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s00335-016-9638-7","volume":"27","author":"M Kaeberlein","year":"2016","unstructured":"Kaeberlein M, Creevy KE, Promislow DEL (2016) The dog aging project: translational geroscience in companion animals. Mamm Genome 27:279\u2013288. https:\/\/doi.org\/10.1007\/s00335-016-9638-7","journal-title":"Mamm Genome"},{"key":"10518_CR19","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.2460\/javma.2002.220.1315","volume":"220","author":"RD Kealy","year":"2002","unstructured":"Kealy RD et al (2002) Effects of diet restriction on life span and age-related changes in dogs. J Am Vet Med Assoc 220:1315\u20131320. https:\/\/doi.org\/10.2460\/javma.2002.220.1315","journal-title":"J Am Vet Med Assoc"},{"key":"10518_CR20","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.cell.2014.10.039","volume":"159","author":"BK Kennedy","year":"2014","unstructured":"Kennedy BK et al (2014) Geroscience: linking aging to chronic disease. Cell 159:709\u2013713. https:\/\/doi.org\/10.1016\/j.cell.2014.10.039","journal-title":"Cell"},{"key":"10518_CR21","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/nri.2016.90","volume":"16","author":"SL Klein","year":"2016","unstructured":"Klein SL, Flanagan KL (2016) Sex differences in immune responses. Nat Rev Immunol 16:626\u2013638. https:\/\/doi.org\/10.1038\/nri.2016.90","journal-title":"Nat Rev Immunol"},{"key":"10518_CR22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0269425","volume":"17","author":"J Labadie","year":"2022","unstructured":"Labadie J et al (2022) Cohort profile: the golden retriever lifetime study (GRLS). PLoS ONE 17:e0269425. https:\/\/doi.org\/10.1371\/journal.pone.0269425","journal-title":"PLoS ONE"},{"key":"10518_CR23","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1017\/S0007114507871686","volume":"99","author":"DF Lawler","year":"2008","unstructured":"Lawler DF et al (2008) Diet restriction and ageing in the dog: major observations over two decades. Br J Nutr 99:793\u2013805. https:\/\/doi.org\/10.1017\/S0007114507871686","journal-title":"Br J Nutr"},{"key":"10518_CR24","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1038\/s41591-019-0673-2","volume":"25","author":"B Lehallier","year":"2019","unstructured":"Lehallier B et al (2019) Undulating changes in human plasma proteome profiles across the lifespan. Nat Med 25:1843\u20131850. https:\/\/doi.org\/10.1038\/s41591-019-0673-2","journal-title":"Nat Med"},{"key":"10518_CR25","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","volume":"186","author":"C L\u00f3pez-Ot\u00edn","year":"2023","unstructured":"L\u00f3pez-Ot\u00edn C, Blasco MA, Partridge L, Serrano M, Kroemer G (2023) Hallmarks of aging: an expanding universe. Cell 186:243\u2013278. https:\/\/doi.org\/10.1016\/j.cell.2022.11.001","journal-title":"Cell"},{"key":"10518_CR26","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/s41467-020-14396-9","volume":"11","author":"EJ M\u00e1rquez","year":"2020","unstructured":"M\u00e1rquez EJ et al (2020) Sexual-dimorphism in human immune system aging. Nat Commun 11:751. https:\/\/doi.org\/10.1038\/s41467-020-14396-9","journal-title":"Nat Commun"},{"key":"10518_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-99349-2","volume":"15","author":"JE McMahon","year":"2025","unstructured":"McMahon JE et al (2025) Translational immune and metabolic markers of aging in dogs. Sci Rep 15:14460. https:\/\/doi.org\/10.1038\/s41598-025-99349-2","journal-title":"Sci Rep"},{"key":"10518_CR28","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.140019","volume":"5","author":"RA Miller","year":"2020","unstructured":"Miller RA et al (2020) Canagliflozin extends life span in genetically heterogeneous male but not female mice. JCI Insight 5:e140019. https:\/\/doi.org\/10.1172\/jci.insight.140019","journal-title":"JCI Insight"},{"key":"10518_CR29","doi-asserted-by":"publisher","first-page":"537","DOI":"10.3758\/s13420-018-0357-7","volume":"46","author":"P Piotti","year":"2018","unstructured":"Piotti P et al (2018) Effect of age on discrimination learning, reversal learning, and cognitive bias in family dogs. Learn Behav 46:537\u2013553. https:\/\/doi.org\/10.3758\/s13420-018-0357-7","journal-title":"Learn Behav"},{"key":"10518_CR30","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1111\/vcp.12459","volume":"46","author":"LB Radakovich","year":"2017","unstructured":"Radakovich LB, Pannone SC, Truelove MP, Olver CS, Santangelo KS (2017) Hematology and biochemistry of aging: evidence of \u201canemia of the elderly\u201d in old dogs. Vet Clin Pathol 46:34\u201345. https:\/\/doi.org\/10.1111\/vcp.12459","journal-title":"Vet Clin Pathol"},{"key":"10518_CR31","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1146\/annurev-animal-051021-080937","volume":"10","author":"A Ruple","year":"2022","unstructured":"Ruple A, MacLean E, Snyder-Mackler N, Creevy KE, Promislow DEL (2022) Dog models of aging. Annu Rev Anim Biosci 10:419\u2013439. https:\/\/doi.org\/10.1146\/annurev-animal-051021-080937","journal-title":"Annu Rev Anim Biosci"},{"key":"10518_CR32","doi-asserted-by":"publisher","first-page":"5395","DOI":"10.1007\/s11357-024-01217-w","volume":"46","author":"SM Schmid","year":"2024","unstructured":"Schmid SM et al (2024) The companion dog as a model for inflammaging: a cross-sectional pilot study. Geroscience 46:5395\u20135407. https:\/\/doi.org\/10.1007\/s11357-024-01217-w","journal-title":"Geroscience"},{"key":"10518_CR33","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1038\/s43587-024-00692-2","volume":"4","author":"X Shen","year":"2024","unstructured":"Shen X et al (2024) Nonlinear dynamics of multi-omics profiles during human aging. Nat Aging 4:1619\u20131634. https:\/\/doi.org\/10.1038\/s43587-024-00692-2","journal-title":"Nat Aging"},{"key":"10518_CR34","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1126\/science.abg7292","volume":"375","author":"O Spadaro","year":"2022","unstructured":"Spadaro O et al (2022) Caloric restriction in humans reveals immunometabolic regulators of health span. Science 375:671\u2013677. https:\/\/doi.org\/10.1126\/science.abg7292","journal-title":"Science"},{"key":"10518_CR35","doi-asserted-by":"publisher","DOI":"10.1186\/s12917-016-0911-5","volume":"12","author":"CR Sundburg","year":"2016","unstructured":"Sundburg CR, Belanger JM, Bannasch DL, Famula TR, Oberbauer AM (2016) Gonadectomy effects on the risk of immune disorders in the dog: a retrospective study. BMC Vet Res 12:278. https:\/\/doi.org\/10.1186\/s12917-016-0911-5","journal-title":"BMC Vet Res"},{"key":"10518_CR36","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s11357-017-9972-z","volume":"39","author":"SR Urfer","year":"2017","unstructured":"Urfer SR et al (2017) A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs. Geroscience 39:117\u2013127. https:\/\/doi.org\/10.1007\/s11357-017-9972-z","journal-title":"Geroscience"},{"key":"10518_CR37","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1007\/s11357-021-00422-1","volume":"43","author":"SR Urfer","year":"2021","unstructured":"Urfer SR et al (2021) Canine cognitive dysfunction (CCD) scores correlate with amyloid beta 42 levels in dog brain tissue. Geroscience 43:2379\u20132386. https:\/\/doi.org\/10.1007\/s11357-021-00422-1","journal-title":"Geroscience"},{"key":"10518_CR38","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1023\/a:1005929801735","volume":"21","author":"P Vajdovich","year":"1997","unstructured":"Vajdovich P, Ga\u00e1l T, Szil\u00e1gyi A, Harnos A (1997) Changes in some red blood cell and clinical laboratory parameters in young and old Beagle dogs. Vet Res Commun 21:463\u2013470. https:\/\/doi.org\/10.1023\/a:1005929801735","journal-title":"Vet Res Commun"},{"key":"10518_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2025.102814","volume":"111","author":"P Zemko","year":"2025","unstructured":"Zemko P et al (2025) Markers of biological age in dogs. Ageing Res Rev 111:102814. https:\/\/doi.org\/10.1016\/j.arr.2025.102814","journal-title":"Ageing Res Rev"},{"key":"10518_CR40","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14127","volume":"23","author":"M Zeng","year":"2024","unstructured":"Zeng M et al (2024) Transcriptomic and intervention evidence reveals domestic dogs as a promising model for anti-inflammatory investigation. Aging Cell 23:e14127. https:\/\/doi.org\/10.1111\/acel.14127","journal-title":"Aging Cell"}],"container-title":["Biogerontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10522-026-10518-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10522-026-10518-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10522-026-10518-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:07:24Z","timestamp":1793833644000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10522-026-10518-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10518"],"URL":"https:\/\/doi.org\/10.1007\/s10522-026-10518-w","relation":{},"ISSN":["1389-5729","1573-6768"],"issn-type":[{"value":"1389-5729","type":"print"},{"value":"1573-6768","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"17 August 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal procedures were approved by the Institutional Animal Care and Use Committee of Anling Biomedical (Shenzhen) Co., Ltd. (approval no. 2025-02-ALSHZH-21). All procedures complied with applicable institutional and national guidelines, the NIH Guide for the Care and Use of Laboratory Animals, and the ARRIVE guidelines.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"172"}}