{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:46:21Z","timestamp":1782927981530,"version":"3.54.5"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institues of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG054442"],"award-info":[{"award-number":["R01AG054442"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The development of chronic inflammation in later life (inflammaging), alongside changes in immune cell profiles and impaired pathogen defense (immunosenescence), contribute to health risk. However, these processes have been hypothesized as adaptive remodeling of the immune system in response to accumulating somatic damage. Here we consider a recently developed theoretical framework to understand their relationship: the Brain\u2013Body Energy Conservation model of aging. This model views immunosenescence as part of an energy conserving response to the rising energy expenditure of inflammaging. This response promotes short-term survival against somatic damage at the expense of future health risk. For example, na\u00efve T cells, which enhance defense against future infections, decline with age, while proteins that suppress the immune response to infection, including interleukin (IL)-10, increase. GDF-15, which similarly suppresses the immune response to infection and is produced in response to chronic inflammation and metabolic stress, also increases with age. We find evidence consistent with this model in the US Health and Retirement Study (HRS, n\u2009=\u20098 184) and UK Biobank (UKB, n\u2009=\u200940\u00a0510). Across both cohorts, the key inflammaging marker tumor necrosis factor receptor (TNFR1) partially mediated the age-related increases in IL-10 and GDF-15. In the HRS flow cytometry data, TNFR1 also mediated age-related decreases in na\u00efve T cells. Finally, we assessed vulnerability to a novel future infection using the UKB medical records data on hospitalization or death from COVID-19 (n\u2009=\u2009586 hospitalized or died). TNFR1, IL-10, and GDF-15, measured pre-pandemic, all partially mediated the age-related increased risk.<\/jats:p>","DOI":"10.1093\/gerona\/glag119","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:43:00Z","timestamp":1778067780000},"source":"Crossref","is-referenced-by-count":1,"title":["Evidence for an energy conservation model of inflammaging and immunosenescence in the US Health and Retirement Study and UK Biobank"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1422-801X","authenticated-orcid":false,"given":"Jacob E","family":"Aronoff","sequence":"first","affiliation":[{"name":"Center for Evolution and Medicine, School of Human Evolution and Social Change, Institute of Human Origins, Arizona State University , Tempe, Arizona,","place":["United 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