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The mechanisms that underlie this phenomenon have nonetheless remained unclear. We found that naive CD8+ T cells in elderly humans were prone to apoptosis and proliferated suboptimally in response to stimulation via the TCR. These abnormalities were associated with dysregulated lipid metabolism under homeostatic conditions and enhanced levels of basal activation. Importantly, reversal of the bioenergetic anomalies with lipid-altering drugs, such as rosiglitazone, almost completely restored the Ag responsiveness of naive CD8+ T cells. Interventions that favor lipid catabolism may therefore find utility as adjunctive therapies in the elderly to promote vaccine-induced immunity against targetable cancers and emerging pathogens, such as seasonal influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).<\/jats:p>","DOI":"10.4049\/jimmunol.2100194","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T10:00:36Z","timestamp":1642154436000},"page":"562-570","source":"Crossref","is-referenced-by-count":39,"title":["Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8+ T Cells in Elderly Humans"],"prefix":"10.1093","volume":"208","author":[{"given":"Francesco","family":"Nicoli","sequence":"first","affiliation":[{"name":"Centre d\u2019Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Universit\u00e9, INSERM U1135 , Paris,","place":["France"]},{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences, University 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