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Further, due to the diverse signals implicated in naive T cell survival, it has been a long-held and conceptually attractive view that they are sustained by active homeostatic control as thymic activity wanes. Here we use multiple modelling and experimental approaches to identify a unified model of naive CD4 and CD8 T cell population dynamics in mice, across their lifespan. We infer that both subsets divide rarely, and progressively increase their survival capacity with cell age. Strikingly, this simple model is able to describe naive CD4 T cell dynamics throughout life. In contrast, we find that newly generated naive CD8 T cells are lost more rapidly during the first 3\u20134 weeks of life, likely due to increased recruitment into memory. We find no evidence for elevated division rates in neonates, or for feedback regulation of naive T cell numbers at any age. We show how confronting mathematical models with diverse datasets can reveal a quantitative and remarkably simple picture of naive T cell dynamics in mice from birth into old age.<\/jats:p>","DOI":"10.7554\/elife.78168","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T06:15:18Z","timestamp":1654755318000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.78168","source":"Crossref","is-referenced-by-count":28,"title":["Towards a unified model of naive T cell dynamics across the lifespan"],"prefix":"10.7554","volume":"11","author":[{"given":"Sanket","family":"Rane","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hj8s172","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center","place":["New York, United States"]},{"id":[{"id":"https:\/\/ror.org\/00hj8s172","id-type":"ROR","asserted-by":"publisher"}],"name":"Irving Institute for Cancer Dynamics, 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