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Beyond merely cataloging taxonomic shifts within specific niches, this concept integrates the cumulative biological effects of microbial community structure, functional homeostasis, ecological interactions, and host regulatory dynamics over time. Accumulating evidence indicates that a deviation between chronological and microbiome age\u2010termed the \u201cmicrobiome age gap\u201d\u2010closely correlates with systemic declines in immunomodulation, metabolic robustness, barrier integrity, and neuroendocrine regulation, positioning it as a potent predictor of healthspan and disease risk. A defining feature of microbial aging is the convergence of divergent ecological niches toward a state of dysbiosis. Despite distinct compositional profiles across the gut, oral cavity, skin, and urogenital tract, these ecosystems commonly exhibit diminished stability, functional remodeling, and altered host\u2013microbe interaction modes with advancing age. Concurrently, site\u2010specific signatures persist, linking microbial shifts to distinct physiological dimensions such as metabolic\u2010inflammatory axes, barrier function, and local hormonal environments. In this review, we systematically delineate the theoretical underpinnings and computational strategies for modeling microbiome age. We synthesize current evidence regarding age\u2010related microbial trajectories across diverse body habitats and propose an integrative framework: microbiome age serves dually as a holistic indicator of systemic aging and a sensitive window into localized organ vulnerability. This perspective not only advances our understanding of host\u2010microbe interactions in aging but also opens new avenues for precision stratification, personalized intervention, and healthspan management.<\/jats:p>","DOI":"10.1002\/imt2.70148","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:27:28Z","timestamp":1783398448000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Microbiome and aging: Trajectories of microbiome age across human ecosystems and their systemic effects"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9723-2398","authenticated-orcid":false,"given":"Zhexin","family":"Ni","sequence":"first","affiliation":[{"name":"Academy of Military Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key 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