{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T14:43:42Z","timestamp":1778078622560,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5P01AG07463"],"award-info":[{"award-number":["5P01AG07463"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cutan Pathol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The human body is composed mostly of water fortified by a variety of proteins, fats, carbohydrates, vitamins, minerals, and other nutrients, all organized into an elegant structurally complex and functionally efficient machine in which our consciousness resides. This heterogeneous assemblage of essential ingredients is enclosed in a container known as the integument, or simply, the skin. The container is as important as its contents; when itself devoid of structural and functional integrity, it will both leak as well as become infused with potentially harmful external agents. As we age, skin loses its integrity, and over time it is not unreasonable to conceive of the skin as becoming progressively \u201cleaky.\u201d With this deterioration, skin becomes dry, scaly, accessible to microbes, pruritic, and inflamed, the latter setting up the potentially vicious cycle known as \u201cinflammaging.\u201d One major example of the effects of chronological aging on the barrier function of skin involves depletion of\n                    <jats:italic>filaggrin<\/jats:italic>\n                    , a 37\u2010kD histidine\u2010rich protein which originates within keratohyaline granules of the epidermis. Some of the consequences of age\u2010related filaggrin depletion may be inferred by experiments of nature known as ichthyosis vulgaris and atopic dermatitis (AD), the latter with atopy being the most common inflammatory disease worldwide. In AD, loss of function mutations in the\n                    <jats:italic>FLG<\/jats:italic>\n                    gene encoding for the filaggrin precursor, profilaggrin, are associated with skin that, as with aging, is also dry, scaly, accessible to microbes, pruritic and inflamed. In this mini\u2010review, AD will be compared and contrasted with aging in terms of the consequences of deficient filaggrin barrier function. The goal is to enhance recognition that one of the most clinically symptomatic and visible signs of aging is a subtle yet ubiquitous form of \u201cdermatitis\u201d due to \u201cleaky\u201d skin, one that may be addressed therapeutically with smart combinatorial strategies that restore the molecular basis for skin barrier dysfunction.\n                  <\/jats:p>","DOI":"10.1111\/cup.14756","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T20:19:02Z","timestamp":1736281142000},"page":"121-124","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Aging Skin: A Dermatitis To Which All Flesh Is Heir?"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9362-5146","authenticated-orcid":false,"given":"George F.","family":"Murphy","sequence":"first","affiliation":[{"name":"Program in Dermatopathology, Department of Pathology Brigham and Women's Hospital\/Mass General Brigham  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523\u20101747.ep12514346"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02991186"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346\u20108138.12631"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241612979"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.033969"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2017.02.280"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5701205"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.06.046"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403\u2010003\u20100448\u2010x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102946"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871528113666140522112003"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.05.042"},{"key":"e_1_2_7_14_1","first-page":"20","article-title":"Topical Corticosteroid Application and the Structural and Functional Integrity of the Epidermal Barrier","volume":"6","author":"Del Rosso J. Q.","year":"2013","journal-title":"Journal of Clinical and Aesthetic Dermatology"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2020.03.007"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7058342"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1364\/BOE.4.000077"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092\u20108674(90)90696\u2010c"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1328"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523\u20101747.2003.12600.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1083\u20108791(03)00288\u2010x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101085\u20107"}],"container-title":["Journal of Cutaneous Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cup.14756","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T22:43:45Z","timestamp":1766011425000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cup.14756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/cup.14756"],"URL":"https:\/\/doi.org\/10.1111\/cup.14756","archive":["Portico"],"relation":{},"ISSN":["0303-6987","1600-0560"],"issn-type":[{"value":"0303-6987","type":"print"},{"value":"1600-0560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,7]]},"assertion":[{"value":"2024-06-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}