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Congratulations to Dr Helen Fraser
27 April 2022
Many congratulations Dr Helen Fraser!
Thank you to the examiners Jürg Bähler from GEE IHA and Ilaria Bellantuono from Sheffield University.
PhD title: Hallmarks of aging predict age-related disease multimorbidities in patients
Abstract: Genetic, environmental, and pharmacological interventions into the aging process can confer resistance to multiple age-related diseases in laboratory animals, including rhesus monkeys. These findings imply that mechanisms of aging, or aging hallmarks, might also contribute to age-related disease multimorbidities in humans. Therefore, aging hallmarks could potentially be targeted to prevent multiple diseases in the same individual. To address this question, 917,645 literature abstracts were text mined followed by manual curation, and they showed strong, non-random associations between age-related diseases and aging hallmarks, which were confirmed by gene set enrichment analysis of GWAS data. Integration of these associations with clinical data from 3.01 million patients showed that age-related diseases associated with each of five aging hallmarks were more likely than expected by chance to be present together in patients. Genetic evidence revealed that innate and adaptive immunity, the intrinsic apoptotic signalling pathway, and the Ras-ERK pathway played a significant role across multiple, diverse, aging hallmark-associated age-related diseases. Network propagation demonstrated that aging hallmarks may explain the occurrence of age-related diseases with an incompletely understood pathogenesis, such as essential tremor. Nine random forest classifiers were trained to accurately detect sentences from scientific abstracts that reported aging hallmarks contributed to the pathogenesis and pathophysiology of diseases. The relevant sentences were displayed in a novel web resource, AgingHallmarkDB, to drive future research in the field. Overall, the findings of this research suggest that aging hallmarks contribute to patterns of human age-related disease multimorbidity and could potentially be targeted to prevent more than one age-related disease in the same patient.