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By integrating single\u2010cell RNA and spatial transcriptomics sequencing, we systematically mapped murine taste bud aging across five developmental stages from neonatal to aged. Our findings reveal that age\u2010associated taste impairment is driven by the progressive depletion of stem\/progenitor cell differentiation capacity, predominantly characterized in the posterior tongue, and mediated by inflamm\u2010aging responses and micro\u2010environmental alterations. Specifically, we identified macrophage infiltration and polarization shifts in aged circumvallate and foliate papillae, underscoring the crucial role of macrophages in age\u2010related taste decline. A co\u2010culture model using taste organoids with conditioned media from polarized macrophage revealed that M1\u2010polarized cells suppress taste organoid proliferation and differentiation. Mechanistically, this inhibition may be mediated by macrophage\u2010derived Thbs1, as recombinant Thbs1 treatment directly suppressed taste progenitor cell expansion in\u00a0vitro. Together, this study provides the first comprehensive spatiotemporal atlas of taste bud aging and identifies novel therapeutic targets for the treatment of age\u2010related taste disorders.<\/jats:p>","DOI":"10.1111\/acel.70674","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:50:41Z","timestamp":1787291441000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Mechanisms of Age\u2010Related Taste Dysfunction Deciphered by Spatiotemporal Transcriptomics"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0115-6414","authenticated-orcid":false,"given":"Wandong","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Life Sciences University of Chinese Academy of Sciences  Beijing China"},{"name":"BGI Research  Qingdao China"},{"name":"BGI Research  Shenzhen 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