Viral Infection as a Contributor to the Burden of Cellular Senescence
This open access paper discusses the evidence for viral infections to increase the burden of cellular senescence, specifically in the context of atherosclerosis and immunosenescence in aging. Viral infection is thought to contribute to both issues, and from what is known of the role of increased numbers of senescent cells in aging, it is possible that increased senescent cells numbers is a significant mechanism. Certainly, we should hope to see researchers establish that a great deal of degenerative aging, accelerated by viral infection or otherwise, can be blamed on the unwanted activities of lingering senescent cells. The development of senolytic therapies to remove senescent cells is a going concern, and the option to live a life without senescent cell accumulation lies in the near future.
The immune system is a versatile and dynamic body organ which offers survival and endurance of human beings in their hostile living environment. However, similar to other cells, immune cells are hijacked by senescence. The ageing immune cells lose their beneficial functions but continue to produce inflammatory mediators which draw other immune and non-immune cells to the senescence loop. Immunosenescence has been shown to be associated with different pathological conditions and diseases, among which atherosclerosis has recently come to light. There are common drivers of both immunosenescence and atherosclerosis; e.g. inflammation, reactive oxygen species (ROS), chronic viral infections, genomic damage, oxidized-LDL, hypertension, cigarette smoke, hyperglycaemia, and mitochondrial failure. Chronic viral infections induce inflammaging, sustained cytokine signaling, reactive oxygen species generation and DNA damage which are associated with atherogenesis.
Recent data indicate that chronic viral infections manipulate the pathways involved in replicative senescence (RS), oncogene-induced senescence (OIS), and possibly genotoxicity-induced senescence (GIS) in immune and non-immune cells. The senescence pathways induced by infectious agents are shared with other senescence inducing stimuli. The induction of senescence in immune cells is more robust in chronic viral infections due to direct stimulation of the immune system by viral antigens. From early childhood, the immune cells of human-beings are challenged with viral infections and fortunately enough, in most cases the virus is contained and even eradicated by immune system. However, continuous encounter with viruses and especially establishment of chronic viral infections in the body results in a state of more inflammatory and less protective immune response.
In atherosclerosis, as one of the old inflammatory conditions and the mother of cardiovascular disease and stroke, immunosenescence is induced both in immune and non-immune cells. Therefore, chronic viral infections, through induction of immunosenescence, may directly or indirectly play a role in development or progression of atherosclerosis. The premature ageing as a result of viral co-infections may also accelerate immunosenescence and inflammatory diseases.