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However, these models differ genetically and physiologically from human aging, posing challenges in translating discoveries to human contexts. In this study, we present a human normal cell aging model based on the development of cytotrophoblasts (CTBs) to syncytiotrophoblasts (STBs) in the placenta. The in\u00a0vitro\u2010derived STBs from human trophoblast stem cells (hTSCs) recapitulate the maturation and major cellular aging features of in\u00a0vivo CTB\u2010STB, including multinucleation, hormone secretion, cell cycle arrest, genome instability, epigenetic changes, activation of endogenous transposable elements, and senescence\u2010associated secretory phenotypes (SASPs). Notably, the progressive senescence in the trophoblast system closely matches the predicted aging trajectory of other human tissue stem cells. Known anti\u2010aging molecules, such as mTOR inhibitors and senolytics, attenuate senescence signals in STBs. The established CGA\u2010EGFP reporter hTSC line enables scalable and quantitative screening and identified candidates with it can be further extended to other context\u2010specific aging processes like that of skin fibroblasts. The hTSC\u2010STB system represents a novel physiologically accelerated cellular aging model, bridges the gap between fundamental aging research and interventions, and prioritizes anti\u2010aging candidates for clinical development.<\/jats:p>","DOI":"10.1111\/acel.70352","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T08:42:39Z","timestamp":1768898559000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Human Cellular System for Studying Normal Aging and for Anti\u2010Aging Discovery"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3064-1752","authenticated-orcid":false,"given":"Zhen","family":"Feng","sequence":"first","affiliation":[{"name":"InnoHK Centre for Translational Stem Cell Biology  Science Park Hong Kong"},{"name":"Shenzhen Key Laboratory of Fertility Regulation, Reproductive Medicine Centre The University of Hong 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