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Inflammaging\u2010induced hyposalivation plays a significant role in aged SGs; however, the mechanisms by which ageing shapes the inflammatory microenvironment of SGs remain unclear. Here, we show that reduced salivary secretion flow rate in aged human and mice SGs is associated with impaired autophagy and increased M1 polarization of macrophages. Our study reveals the crucial roles of SIRT6 in regulating macrophage autophagy and polarization through the PI3K\/AKT\/mTOR pathway, as demonstrated by generating two conditional knock out mice. Furthermore, triptolide (TP) effectively rejuvenates macrophage autophagy and polarization via targeting this pathway. We also design a local delivery of TP\u2010loaded apoptotic extracellular vesicles (ApoEVs) to improve age\u2010related SGs dysfunction therapeutically. Collectively, our findings uncover a previously unknown link between SIRT6\u2010regulated autophagy and macrophage polarization in age\u2010mediated hyposalivation, while our locally therapeutic strategy exhibits potential preventive effects for age\u2010related hyposalivation.<\/jats:p>","DOI":"10.1111\/cpr.13714","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T03:39:48Z","timestamp":1721014788000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Impaired autophagy\u2010mediated macrophage polarization contributes to age\u2010related hyposalivation"],"prefix":"10.1111","volume":"57","author":[{"given":"Zhili","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory Cultivation Base of Research, Prevention and Treatment for 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