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This study aimed to determine the following: whether Sirt1 and serum vitamin D decreased with physiological aging, promoting senescence\u2010associated pulmonary fibrosis by activating TGF\u2010\u03b21\/IL\u201011\/MEK\/ERK signaling, whether Sirt1 overexpression prevented TGF\u2010\u03b21\/IL\u201011\/MEK\/ERK signaling\u2010mediated senescence\u2010associated pulmonary fibrosis in vitamin D\u2010deficient (\n                    <jats:italic>Cyp27b1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) mice, and whether Sirt1 downregulated\n                    <jats:italic>IL\u201011<\/jats:italic>\n                    expression transcribed by TGF\u2010\u03b21\/Smad2 signaling through deacetylating histone at the\n                    <jats:italic>IL\u201011<\/jats:italic>\n                    promoter in pulmonary fibroblasts. Bioinformatics analysis with RNA sequencing data from pulmonary fibroblasts of physiologically aged mice was conducted for correlation analysis. Lungs from young and physiologically aged wild\u2010type (WT) mice were examined for cell senescence, fibrosis markers, and TGF\u2010\u03b21\/IL\u201011\/MEK\/ERK signaling proteins, and 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    and IL\u201011 levels were detected in serum. Nine\u2010week\u2010old WT,\n                    <jats:italic>Sirt1<\/jats:italic>\n                    mesenchymal transgene (\n                    <jats:italic>Sirt1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Tg<\/jats:italic>\n                    <\/jats:sup>\n                    ),\n                    <jats:italic>Cyp27b1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    , and\n                    <jats:italic>Sirt1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Tg<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>Cyp27b1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice were observed the pulmonary function, aging, and senescence\u2010associated secretory phenotype and TGF\u2010\u03b21\/IL\u201011\/MEK\/ERK signaling. We found that pulmonary Sirt1 and serum vitamin D decreased with physiological aging, activating TGF\u2010\u03b21\/IL\u201011\/MEK\/ERK signaling, and promoting senescence\u2010associated pulmonary fibrosis. Sirt1 overexpression improved pulmonary dysfunction, aging, DNA damage, senescence\u2010associated secretory phenotype, and fibrosis through downregulating TGF\u2010\u03b21\/IL\u201011\/MEK\/ERK signaling in\n                    <jats:italic>Cyp27b1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Sirt1 negatively regulated\n                    <jats:italic>IL\u201011<\/jats:italic>\n                    expression through deacetylating H3K9\/14ac mainly at the region from \u2212871 to \u2212724 of\n                    <jats:italic>IL\u201011<\/jats:italic>\n                    promoter, also the major binding region of Smad2 which regulated\n                    <jats:italic>IL\u201011<\/jats:italic>\n                    expression at the transcriptional level, and subsequently inhibiting TGF\u2010\u03b21\/IL\u201011\/MEK\/ERK signaling in pulmonary fibroblasts. This signaling in aging fibroblasts could be a therapeutic target for preventing senescence\u2010associated pulmonary fibrosis induced by vitamin D deficiency.\n                  <\/jats:p>","DOI":"10.1111\/acel.13680","type":"journal-article","created":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T07:09:55Z","timestamp":1659164995000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Sirt1 overexpression improves senescence\u2010associated pulmonary fibrosis induced by vitamin D deficiency through downregulating\n                    <i>IL\u201011<\/i>\n                    transcription"],"prefix":"10.1111","volume":"21","author":[{"given":"Jiawen","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Human Anatomy, Research Centre for Bone and Stem Cells, Key Laboratory for Aging &amp; Disease The State Key Laboratory of Reproductive Medicine, Nanjing Medical University  Nanjing 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Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Research Centre for Bone and Stem Cells, Key Laboratory for Aging &amp; Disease The State Key Laboratory of Reproductive Medicine, Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Research Centre for Bone and Stem Cells, Key Laboratory for Aging &amp; Disease The State Key Laboratory of Reproductive Medicine, Nanjing Medical University  Nanjing China"},{"name":"The Laboratory Centre for Basic Medical Sciences Nanjing Medical University  Nanjing 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