Interactomics: dozens of viruses, co-evolving with humans, including the influenza A virus, may actively distort human ageing.

Some viruses (e.g. HIV-1, SARS-CoV-2) have been experimentally proposed to accelerate features of human ageing and of cellular senescence. These observations, along with evolutionary considerations on viral fitness, raised the more general puzzling hypothesis that, beyond documented sources in human genetics, ageing in our species may also depend on virally-encoded interactions distorting our ageing to the benefits of diverse viruses. Accordingly, we designed systematic network-based analyses of the human and viral protein interactomes, which unraveled dozens of viruses encoding proteins experimentally demonstrated to interact with proteins from pathways associated with human ageing, including cellular senescence. We further corroborated our predictions that specific viruses interfere with human ageing using published experimental evidence and transcriptomic data; identifying influenza A virus (subtype H1N1) as a major candidate age-distorter, notably through manipulation of cellular senescence. By providing original evidence that viruses may convergently contribute to the evolution of numerous age-associated pathways through co-evolution, our network- and bipartite network-based methodology supports an ecosystemic study of ageing, also searching for genetic causes of ageing outside a focal ageing species. Our findings, predicting age-distorters and targets for anti-ageing therapies amongst human viruses, could have fundamental and practical implications for evolutionary biology, ageing study, virology, medicine and demography.