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The concept is illustrated by the case of essential thrombocythemia (ET). Patients with ET have substantially elevated platelets and are therefore expected to have increased thrombotic events leading to reduced life expectancy. However, patients with ET do not have reduced life expectancy. A possible explanation is that elevated platelets produce higher levels of platelet factor 4 (PF4), which has been found to reduce age-associated decline in immune and cognitive function in mice and has been suggested as a treatment for age-associated illness. The benefit of elevated PF4 is hypothesized to balance the increased morbidity from hematological causes. Searches for other indications where a well-defined pathology is not associated with concomitant reduction in overall mortality may be a route to identifying factors that could protect against, prevent, or treat chronic disease.<\/jats:p>","DOI":"10.1089\/rej.2023.0066","type":"journal-article","created":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T10:52:00Z","timestamp":1712400720000},"page":"110-114","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Platelet Factor 4 and Longevity of Patients with Essential Thromobocythemia: An Example of Antagonistic Pathogenic Pleiotropy"],"prefix":"10.1177","volume":"27","author":[{"given":"William","family":"Bains","sequence":"first","affiliation":[{"name":"Five Alarm Bio Ltd., Hauxton, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.110.122549"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.hdy.6884400"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.2307\/2406060"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/emph\/eoy033"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00239-019-09923-2"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/54.12.B521"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-003-0776-3"},{"key":"e_1_3_5_9_2","article-title":"Biological constraint as a cause of aging","author":"Gems D","year":"2022","unstructured":"Gems D, , Kern C. 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