4.7 Article

Biological mechanisms of aging predict age-related disease co-occurrence in patients

期刊

AGING CELL
卷 21, 期 4, 页码 -

出版社

WILEY
DOI: 10.1111/acel.13524

关键词

age-related disease; aging; aging hallmarks; genetics; multimorbidity

资金

  1. UK Medical Research Council [MR/N013867/1]
  2. Wellcome Trust Strategic Award
  3. European Research Council (ERC) under the European Union [741989]
  4. Max Planck Society
  5. German Federal Ministry of Education and Research (BMBF) [HiGHmed 01ZZ1802U]
  6. Wellcome Trust [WT 110284/Z/15/Z]
  7. Dunhill Medical Trust [RPGF1806/67]
  8. BHF Accelerator Award [AA/18/6/34223]
  9. German Research Foundation [CRC1310, 325931972]
  10. European Research Council (ERC) [741989] Funding Source: European Research Council (ERC)
  11. Wellcome Trust [110284/Z/15/Z] Funding Source: Wellcome Trust

向作者/读者索取更多资源

This study found that interventions in the aging process can confer resistance to multiple age-related diseases in laboratory animals. By analyzing literature abstracts and clinical data, the researchers discovered associations between age-related diseases and aging mechanisms in humans. They also identified specific mechanisms that are associated with diverse age-related diseases. This suggests that targeting these mechanisms could potentially prevent multimorbidity.
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 individual mechanisms of aging might contribute to the co-occurrence of age-related diseases in humans and could be targeted to prevent these conditions simultaneously. To address this question, we text mined 917,645 literature abstracts followed by manual curation and found strong, non-random associations between age-related diseases and aging mechanisms in humans, 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 mechanisms were more likely than chance to be present together in patients. Genetic evidence revealed that innate and adaptive immunity, the intrinsic apoptotic signaling pathway and activity of the ERK1/2 pathway were associated with multiple aging mechanisms and diverse age-related diseases. Mechanisms of aging hence contribute both together and individually to age-related disease co-occurrence in humans and could potentially be targeted accordingly to prevent multimorbidity.

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