{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T10:09:06Z","timestamp":1784110146373,"version":"3.55.0"},"reference-count":83,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T00:00:00Z","timestamp":1598572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Adipose tissue is recognized as a major source of systemic inflammation with age, driving age\u2010related tissue dysfunction and pathogenesis. Macrophages (M\u03c6) are central to these changes yet adipose tissue M\u03c6 (ATMs) from aged mice remain poorly characterized. To identify biomarkers underlying changes in aged adipose tissue, we performed an unbiased RNA\u2010seq analysis of ATMs from young (8\u2010week\u2010old) and healthy aged (80\u2010week\u2010old) mice. One of the genes identified, V\u2010set immunoglobulin\u2010domain\u2010containing 4 (VSIG4\/CRIg), encodes a M\u03c6\u2010associated complement receptor and B7 family\u2010related immune checkpoint protein. Here, we demonstrate that <jats:italic>Vsig4<\/jats:italic> expression is highly upregulated with age in perigonadal white adipose tissue (gWAT) in two mouse strains (inbred C57BL\/6J and outbred NIH Swiss) independent of gender. The accumulation of VSIG4 was mainly attributed to a fourfold increase in the proportion of VSIG4<jats:sup>+<\/jats:sup> ATMs (13%\u201352%). In a longitudinal study, VSIG4 expression in gWAT showed a strong correlation with age within a cohort of male and female mice and correlated strongly with physiological frailty index (PFI, a multi\u2010parameter assessment of health) in male mice. Our results indicate that VSIG4 is a novel biomarker of aged murine ATMs. VSIG4 expression was also found to be elevated in other aging tissues (e.g., thymus) and was strongly induced in tumor\u2010adjacent stroma in cases of spontaneous and xenograft lung cancer models. VSIG4 expression was recently associated with cancer and several inflammatory diseases with diagnostic and prognostic potential in both mice and humans. Further investigation is required to determine whether VSIG4\u2010positive M\u03c6 contribute to immunosenescence and\/or systemic age\u2010related deficits.<\/jats:p>","DOI":"10.1111\/acel.13219","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T15:23:12Z","timestamp":1598628192000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Immune checkpoint protein VSIG4 as a biomarker of aging in murine adipose tissue"],"prefix":"10.1111","volume":"19","author":[{"given":"Brandon M.","family":"Hall","sequence":"first","affiliation":[{"name":"Everon Biosciences Inc  Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoli S.","family":"Gleiberman","sequence":"additional","affiliation":[{"name":"Everon Biosciences Inc  Buffalo NY 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