Immune System Aging as Only Loosely Coupled to the Rest of Aging
The immune system ages along with everything else in the body, entering the states of immunosenescence and inflammaging. Immunosenescence is a growing ineffectiveness of the immune response, while inflammaging is a constant and inappropriate activation of the immune response. Researchers here make the point that immune aging might be thought of as being only loosely coupled to the rest of aging, as it is possible, for example, for chronic infections such as HIV to bring on aspects of immunosenescence and inflammaging far earlier in life than would otherwise be the case.
Aging has been associated with a myriad of both acute and chronic diseases. At the core of these diseases, the change in the host immune system with age could either have contributed to the cause as it is the host main defence mechanism against foreign pathogens or its functionality being impacted by these diseases and conditions. However, the change in the immune system with age could also be seen as an adaptation process to save resources for the host rather than it being detrimental.
This is because developing competent naïve T cells has only about 1-2% success rate due to the various stringent selection processes. Therefore, biological processes such as thymic involution could be seen as advantageous to the host from an energetic or evolutionary point of view. One of the main arguments that thymic involution is detrimental to the host is due to the reduction of naïve T cells being produced, leading to a narrower repertoire for new antigens and perhaps reduced vaccine efficacy often observed in the elderly, while this may have been a successful programmed process for the shorter-lived humans in the past centuries and before the extended human lifespan has revealed the probable need to reverse this adaptation.
Chronic low-grade inflammation is a commonality between individuals that exhibit chronic stress, obesity, aging, sleep loss, gut dysbiosis, CMV infection, dysregulated immune cell functions, and accumulation of SASP cells such as fibroblasts. Chronic low-grade inflammation is defined as a higher baseline of pro-inflammatory cytokines in the circulation though the source and specific cytokines might differ slightly between these "diseases" in the absence of foreign pathogen infection. In terms of impaired immunity, both human and animal studies have shown that chronic stress reduces various immune functional capacities. The presence of impaired immunity and low-grade chronic inflammation could be the underlying factors that exacerbate pathology in various disease contexts.
Thus, it is important that we redefine and stress that the definition of immunosenescence is the dysfunctionality of the immune system and should encompass some features of low-grade chronic inflammation. Though this phenomenon is often seen in aged individuals, it is also possible in younger adults as it could be "accelerated immunosenescence", especially for T cells, as shown in CMV and HIV seropositive young patients. Even early in life, the impact of CMV can be observed. This highlights that other factors other than chronological age could determine this level of senescence of the immune system, especially for T cells which are prone to proliferation. Overall, rethinking the causing agents and implications of immunosenescence will help shift the perspective that this phenomenon is not attributed to age alone, especially with the global rising rate of obesity and chronic stress of modern-day life in the young.