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Here we investigate how age-related pathology mediates the effect of genetic and environmental interventions on lifespan in\n                    <jats:italic>C. elegans<\/jats:italic>\n                    by means of a data-driven approach employing machine learning (ML). To this end, extensive data on how diverse determinants of lifespan (sex, nutrition, genotype, mean lifespan range: 7.5 to 40 days) affect patterns of age-related pathology was gathered. This revealed that different life-extending treatments result in distinct patterns of suppression of senescent pathology. By analysing the differential effects on mid-life pathology levels and lifespan, the ML models developed were able to predict lifespan variation, explaining 79% of the variance. Levels of pathology in the pharynx and intestine proved to be the strongest predictors of lifespan. This suggests that elderly\n                    <jats:italic>C. elegans<\/jats:italic>\n                    die predominantly from late-life disease affecting these organs. In addition, we noted profound sex differences in age-related pathology: the striking age-related pathologies in hermaphrodites affecting organs linked to reproduction are absent from males, suggesting that reproductive death may be hermaphrodite limited.\n                  <\/jats:p>","DOI":"10.1038\/s42003-025-09012-9","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T12:41:52Z","timestamp":1763728912000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Machine learning predicts lifespan and suggests underlying causes of death in aging C. elegans"],"prefix":"10.1038","volume":"8","author":[{"given":"Carina C.","family":"Kern","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petru","family":"Manescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Cuffaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-9121","authenticated-orcid":false,"given":"Catherine","family":"Au","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann F.","family":"Gilliat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"van Schelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-6984","authenticated-orcid":false,"given":"Marina","family":"Ezcurra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6653-4676","authenticated-orcid":false,"given":"David","family":"Gems","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"9012_CR1","doi-asserted-by":"publisher","first-page":"e599","DOI":"10.1016\/S2468-2667(19)30222-1","volume":"4","author":"J Pearson-Stuttard","year":"2019","unstructured":"Pearson-Stuttard, J., Ezzati, M. & Gregg, E. 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