Immunosenescence and Loss of Resistance to Viral Infection

The authors of this open access review paper discuss what is known of the age-related failure of the immune system, with a focus on the consequences for viral infection and vaccination effectiveness. The elderly suffer greatly because the immune system falters in its ability to protect against pathogens, a dysfunction that has numerous root causes. The atrophy of the thymus, reducing the supply of new T cells to a trickle; the disruption of hematopoietic stem cell function, reducing the pace of production of all immune cells; the fibrosis of lymph nodes, rendering it hard for immune cells to coordinate with one another; the accumulation of broken and harmful immune cell populations absent a supply of undamaged reinforcements. Potential strategies exist to address all of these issues; they must just be brought to realization by the research and development communities.

Immunosenescence is a major cause of increased incidence and severity of viral infections in the elderly, and contributes to impaired immunogenicity and efficacy of vaccines. Understanding the biological basis for age-associated alterations in viral immunity and vaccine immunogenicity is a challenge with substantial clinical importance. Subsequently, the use of systems biology approaches in combination with computational model systems will be crucial to understand the complexity of age-associated changes in the immune system by identifying molecular networks that orchestrate immunity to vaccinations in humans and potentially define correlates of protection.

Given the plastic nature of aging and rapidly growing field of systems biology, molecular profiling of the aging-related changes is increasingly being examined at a single cell level by high-throughput omics technologies, including genomics, metagenomics, transcriptomics, and metabolomics. Specially, aging of the immune cells is affected by changes in homeostasis via cytokine levels, and by modifications in the metabolic pathways. Caloric restrictions (CR) affected a marked improvement in the maintenance and/or production of naïve T cells and the consequent preservation of TCR repertoire diversity. Furthermore, CR also improved T cell function and reduced production of inflammatory cytokines by memory T cells, suggesting that CR can delay T cell senescence and potentially contribute to extended lifespan by reducing susceptibility to infectious diseases.

A key area for future exploration in the immunosenescence field is the role of the secondary lymphoid organs as a critical partner in the development and function of the aging human immune system. It will be important to analyze age-related changes in secondary lymphoid organs, lymph nodes and spleen, given the aging-associated decrease in the size of lymph nodes. Lymph nodes not only serve as the key initiating region of the immune response, but they also play an important role in maintaining naive lymphocytes.

Next, investigation of how extracellular vesicles (EVs) are linked to aging could be a promising area of interest. EVs are membrane-bound vesicles released by multiple cell types that include immune cells. Evidence from cellular models suggests that exosomes released by macrophages from older are more pro-inflammatory than those released by macrophage from younger. In particular, mRNA levels of IL-6 and IL-12, but not TNF-α, in macrophage-derived exosomes were significantly higher in serums of older subjects. Given that EVs play an important role in immune cell network and cellular senescence, the profiles of secretome and the function of senescent immune cells will soon be revealed as the EV research field progresses.



I just watched a presentation by Gritstone Oncology ,a company that develops neoantigen vaccines against cancer, interesting stuff, companies like this should be interested in a more functional immune system.

Posted by: Tom at January 23rd, 2020 6:21 AM

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