{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:52:53Z","timestamp":1790790773403,"version":"4.1.0"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["2020-01660"],"award-info":[{"award-number":["2020-01660"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003792","name":"Swedish Brain Foundation","doi-asserted-by":"crossref","award":["FO2022-0079"],"award-info":[{"award-number":["FO2022-0079"]}],"id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008590","name":"Swedish Stroke Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008590","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Regional Research Support from the Southern Swedish Healthcare Region"},{"name":"Swedish Government Initiative for Strategic Research Areas"},{"name":"Swedish Heart and Lung Foundation","award":["20210672"],"award-info":[{"award-number":["20210672"]}]},{"name":"Swedish Government","award":["2022-Projekt0279"],"award-info":[{"award-number":["2022-Projekt0279"]}]},{"name":"Swedish Government","award":["2022-Project0145"],"award-info":[{"award-number":["2022-Project0145"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01-NS114045"],"award-info":[{"award-number":["1R01-NS114045"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Freemasons Lodge of Instruction Eos in Lund"},{"DOI":"10.13039\/501100003252","name":"Lund University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003252","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003252","name":"Lund University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003252","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Sk\u00e5ne University"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Aging profoundly affects the immune system leading to an increased propensity for inflammation. Age-related dysregulation of immune cells is implicated in the development and progression of numerous age-related diseases such as: cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Monocytes and monocyte-derived macrophages, being important players in the inflammatory response, significantly influence the aging process and the associated increase in inflammatory disease risk. Ischemic stroke is among age-related diseases where inflammation, particularly monocyte-derived macrophages, plays an important deteriorating role but could also strongly promote post-stroke recovery. Also, biological sex influences the incidence, presentation, and outcomes of ischemic stroke, reflecting both biological differences between men and women. Here, we studied whether human peripheral blood monocyte subtype (classical, intermediate, and non-classical) expression of genes implicated in stroke-related inflammation and post-stroke tissue regeneration depends on age and sex. A flow cytometry analysis of blood samples from 44 healthy volunteers (male and female, aged 28 to 98) showed that in contrast to other immune cells, the proportion of NK-cells increased in females. The proportion of B-cells decreased in both sexes with age. Gene expression analysis by qPCR identified several genes differentially correlating with age and sex within different monocyte subtypes. Interestingly,\n                    <jats:italic>ANXA1<\/jats:italic>\n                    and\n                    <jats:italic>CD36<\/jats:italic>\n                    showed a consistent increase with aging in all monocytes, specifically in intermediate (\n                    <jats:italic>CD36<\/jats:italic>\n                    ) and intermediate and non-classical (\n                    <jats:italic>ANXA1<\/jats:italic>\n                    ) subtypes. Other genes (\n                    <jats:italic>IL-1\u03b2<\/jats:italic>\n                    ,\n                    <jats:italic>S100A8<\/jats:italic>\n                    ,\n                    <jats:italic>TNF\u03b1<\/jats:italic>\n                    ,\n                    <jats:italic>CD64<\/jats:italic>\n                    ,\n                    <jats:italic>CD33<\/jats:italic>\n                    ,\n                    <jats:italic>TGF\u03b21<\/jats:italic>\n                    ,\n                    <jats:italic>TLR8<\/jats:italic>\n                    ,\n                    <jats:italic>CD91<\/jats:italic>\n                    ) were differentially changed in monocyte subtypes with increasing age. Most age-dependent gene changes were differentially expressed in female monocytes. Our data shed light on the nuanced interplay of age and sex in shaping the expression of inflammation- and regeneration-related genes within distinct monocyte subtypes. Understanding these dynamics could pave the way for targeted interventions and personalized approaches in post-stroke care, particularly for the aging population and individuals of different sexes.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0300946","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T13:27:48Z","timestamp":1730294868000},"page":"e0300946","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Human monocyte subtype expression of neuroinflammation- and regeneration-related genes is linked to age and sex"],"prefix":"10.1371","volume":"19","author":[{"given":"Juliane F.","family":"Tamp\u00e9","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Monni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Palma-Tortosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"Brog\u00e5rdh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotta","family":"B\u00f6iers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne G.","family":"Lindgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2296-2449","authenticated-orcid":true,"given":"Zaal","family":"Kokaia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"issue":"10","key":"pone.0300946.ref001","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: a new immune-metabolic viewpoint for age-related diseases","volume":"14","author":"C Franceschi","year":"2018","journal-title":"Nat Rev Endocrinol"},{"issue":"7446","key":"pone.0300946.ref002","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature12034","article-title":"Macrophage biology in development, homeostasis and disease","volume":"496","author":"TA Wynn","year":"2013","journal-title":"Nature"},{"issue":"4","key":"pone.0300946.ref003","doi-asserted-by":"crossref","first-page":"114073","DOI":"10.1016\/j.celrep.2024.114073","article-title":"Aging-related defects in macrophage function are driven by MYC and USF1 transcriptional programs","volume":"43","author":"CE Moss","year":"2024","journal-title":"Cell Rep"},{"issue":"15","key":"pone.0300946.ref004","doi-asserted-by":"crossref","first-page":"4182","DOI":"10.1523\/JNEUROSCI.4317-15.2016","article-title":"Monocyte-Derived Macrophages Contribute to Spontaneous Long-Term Functional Recovery after Stroke in Mice","volume":"36","author":"S Wattananit","year":"2016","journal-title":"J Neurosci"},{"issue":"1","key":"pone.0300946.ref005","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1189\/jlb.69.1.11","article-title":"Heterogeneity of human peripheral blood monocyte subsets","volume":"69","author":"E Grage-Griebenow","year":"2001","journal-title":"J Leukoc Biol"},{"issue":"1","key":"pone.0300946.ref006","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nri978","article-title":"Alternative activation of macrophages","volume":"3","author":"S. 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