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Understanding the underlying biological mechanisms contributing to sleep disorders is crucial for developing targeted interventions. In this study, we measured 355 plasma proteins in an elderly Japanese cohort (\n                    <jats:italic>n<\/jats:italic>\n                    =77) using a high-throughput proteomic platform. Additionally, we collected over 25,000 person-days of physical activity and sleep behavior data from wrist-worn wearable devices, focusing on total sleep time (TST) across 24\u00a0h and daytime sleep. Fragmented sleep was observed as one of the most prevalent sleep disturbances in this population. In protein expression analysis, we identified 9 protein biomarkers associated with increased secondary sleep TST, defined as additional sleep episodes outside of the main sleep episode within 24\u00a0h. These findings may suggest disruptions in circadian rhythms or underlying health conditions. Functional analysis revealed that biological processes related to inflammation play a significant role in regulating sleep behavior. Further analysis showed an association of 12 proteins with daytime sleep and 5 proteins with afternoon sleep. Overall, this study identified inflammatory biomarkers and biological processes associated with sleep behavior in the elderly, presenting promising opportunities for developing diagnostic tools and targeted clinical interventions.\n                  <\/jats:p>","DOI":"10.1007\/s11357-025-01565-1","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T17:14:14Z","timestamp":1744132454000},"page":"4623-4634","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Associations between plasma proteomic signatures and secondary sleep in older adults"],"prefix":"10.1007","volume":"47","author":[{"given":"Kaushalya","family":"Madhawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Svensson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoang","family":"Nt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ung-il","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko Kishi","family":"Svensson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"1565_CR1","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.sleep.2016.07.019","volume":"24","author":"GN Pires","year":"2016","unstructured":"Pires GN, Bezerra AG, Tufik S, Andersen ML. 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