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The thyroid\u2010stimulating hormone (TSH) levels increase in healthy elderly populations. However, whether the thyroid undergoes cellular senescence and how this relates to thyroid hormone (TH) synthesis remain unclear. To investigate the molecular and functional characteristics of thyroid aging, we performed scRNA\u2010seq on human thyroids from young, middle\u2010aged, and old groups, identifying thousands of aging\u2010related differentially expressed genes and revealing the early onset of aging in the middle\u2010aged group. As aging progresses, the expression levels of genes related to TH synthesis increase, suggesting that epithelial cells (EPI) adjust their gene expression in response to elevated TSH levels. Additionally, the senescence\u2010associated secretory phenotype (SASP) in EPI cells is progressively enhanced with aging. We identified a subgroup of epithelial cells (CDKN1A_EPI) characterized by reduced functionality and significantly elevated levels of cellular senescence. We found that the core circadian rhythm gene <jats:italic>BMAL1<\/jats:italic> (<jats:italic>ARNTL<\/jats:italic>) is downregulated during aging. We further validated this finding using the thyroid\u2010specific <jats:italic>Bmal1<\/jats:italic> knockout mouse model, showing that the downregulation of <jats:italic>Bmal1<\/jats:italic> inhibits the expression of <jats:italic>Nfkbia<\/jats:italic> (<jats:italic>NF\u2010\u03baB inhibitor alpha<\/jats:italic>), thereby accelerating cellular senescence and impairing hormone synthesis. Finally, through cell line experiments and transcriptome sequencing, we confirmed that <jats:italic>BMAL1<\/jats:italic> knockout leads to decreased <jats:italic>NFKBIA<\/jats:italic> expression, promoting thyroid cellular\u00a0senescence. Our study demonstrates that circadian rhythm disruption accelerates cellular senescence in the thyroid and exacerbates the decline of thyroid function, providing a novel theoretical foundation for understanding thyroid aging mechanisms and maintaining thyroid function stability.<\/jats:p>","DOI":"10.1111\/acel.70119","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T08:58:54Z","timestamp":1748422734000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Circadian Gene <scp><i>BMAL1<\/i><\/scp> Regulation of Cellular Senescence in Thyroid Aging"],"prefix":"10.1111","volume":"24","author":[{"given":"Dandan","family":"Zong","sequence":"first","affiliation":[{"name":"Department of Endocrinology Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou 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