Interactomics: Dozens of Viruses, Co-evolving With Humans, Including the Influenza A Virus, may Actively Distort Human Aging

Abstract

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.

HCV spontaneous clearers showed low senescence profile in people living with HIV under long ART

“…There is evidence that senescence contributes to the pathophysiology of respiratory viral infections, 34 and a recent report has observed that viruses may convergently contribute to the evolution of human aging. 35 Thus, we assumed that all patients suffered from viral infections in a similar proportion and all of them were recruited previous COVID-19 pandemic.…”

“…However, the importance of senescence in acute inflammatory conditions such as respiratory viral infections has been less approached until the COVID‐19 outbreak, as it has been mainly addressed in chronic infections. There is evidence that senescence contributes to the pathophysiology of respiratory viral infections, 34 and a recent report has observed that viruses may convergently contribute to the evolution of human aging 35 . Thus, we assumed that all patients suffered from viral infections in a similar proportion and all of them were recruited previous COVID‐19 pandemic.…”

Situating physiology within evolutionary theory

“…Pro-and eukaryotes alike are furthermore prone to viral infections (La Scola et al, 2003) and over the course of eukaryotic evolution, multicellular organisms J Physiol 602.11 have further coevolved with a varying infectious and symbiotic viriome and microbiome that has consistently contributed to organismal health and disease (Moelling, 2020;Roossinck, 2015;Villarreal & Ryan, 2019;Witzany, 2020;Gontier & Sukhoverkhov 2023), and, as recently shown, organismal ageing (Teulière et al, 2023).…”

Spreading Senescent Cells’ Burden and Emerging Therapeutic Targets for Frailty

“…Moreover, cellular senescence has also been described as an anti-viral mechanism [ 77 , 78 , 79 , 80 , 81 , 82 ]; thus, it is unsurprising that many viruses, including SARS-CoV-2, have been shown to directly induce cellular senescence [ 80 , 83 , 84 ]. Recently, a systematic network-based analysis of the human and viral protein interactomes produced a list of the top viral candidates predicted to influence human aging; among these, the influenza A virus (subtype H1N1) has emerged as the leading candidate, primarily due to its genetic, encoded potential to interact with cellular senescence [ 85 ].…”