Biomarkers for Immunosenescence
The aging immune system exhibits a declining ability to destroy pathogens and dysfunctional, harmful cells. This is known as immunosenescence. There are ways to assess immune cell populations and their characteristics to measure the degree of immunosenescence, but this is comparatively costly and cannot be used on banked samples. Researchers here ask whether combinations of circulating proteins can instead be used to assess the degree of immunosenescence from a blood sample, and propose a few such biomarkers based on their analysis.
Inflammaging, the characteristics of immunosenescence, is characterized by continuous chronic inflammation that could not be resolved. It not only affects older people but can also occur in young individuals, especially those suffering from chronic inflammatory conditions such as autoimmune disease, malignancy, or chronic infection. This condition led to altered immune function and as consequent immune function is reduced. Detection of immunosenescence has been done by examining the immune risk profile (IRP), which uses flow cytometry. These tests are not always available in health facilities, especially in developing countries and require fresh whole blood samples. Therefore, it is necessary to find biomarkers that can be tested using stored serum to make it easier to refer to the examination.
Here we proposed an insight for soluble biomarkers which represented immune cells activities and exhaustion, namely sCD163, sCD28, sCD80, and sCTLA-4. Those markers were reported to be elevated in chronic diseases that caused early aging and easily detected from serum samples using ELISA method, unlike IRP. Therefore, we conclude that these soluble markers are beneficial to predict the pathological condition of immunosenescence.
User:
There is some evidence that the adaptive immune system is limited. Does the purponderance of scientific evidence suggest that is the case? Would you expect individuals exposed to more novel pathogens to express more inflammaging than people in morre isolated and sterile environments?
Bimini:
The concept that the adaptive immune system has limitations is indeed supported by a substantial body of scientific evidence, particularly relating to aging and the phenomenon of immunosenescence. Immunosenescence refers to the gradual deterioration of the immune system brought on by natural age advancement, which affects both the innate and adaptive components of the immune response. This decline manifests in several ways, including reduced production of naïve lymphocytes, accumulation of memory T cells, decreased diversity of the T-cell receptor (TCR) repertoire, and impaired function of B cells. These changes can lead to a diminished ability to respond to new infections and vaccines, increased susceptibility to disease, and a general chronic low-grade inflammation known as inflammaging.
Inflammaging is characterized by increased levels of pro-inflammatory cytokines in the absence of any overt infection and is considered a significant risk factor for morbidity and mortality in older adults. It is a complex process influenced by several factors, including lifelong antigenic load, which encompasses exposure to pathogens, chronic viral infections, and possibly the microbiota.
Adaptive Immune System Limitations and Pathogen Exposure
The "hygiene hypothesis" suggests that exposure to a certain level of microbial environments during early life is essential for the proper development of the immune system. It implies that too sterile of an environment might lead to an increased likelihood of autoimmune diseases and allergies due to an undertrained immune system. Conversely, the "antigenic load hypothesis" posits that chronic exposure to a wide variety of pathogens can overburden the immune system, particularly the adaptive immune component, leading to an exhausted state that contributes to immunosenescence and inflammaging.
Novel Pathogens and Inflammaging
Regarding the question of whether exposure to more novel pathogens results in more inflammaging compared to those in more isolated and sterile environments, the relationship is nuanced. On one hand, repeated or chronic exposure to pathogens can indeed keep the immune system in a state of heightened alert, leading to persistent low-grade inflammation. On the other hand, a certain level of pathogen exposure, especially during the critical period of immune system development, is thought to be necessary for training the immune response to distinguish between self, non-self, and harmless antigens effectively.
In theory, individuals in extremely sterile environments might not develop a fully robust immune system, potentially leading them to overreact to benign antigens or to not react appropriately to harmful ones, possibly increasing the risk of inflammatory disorders and autoimmune diseases. However, this does not necessarily mean they would experience less inflammaging since inflammaging is influenced by a multitude of factors beyond pathogen exposure, including genetic predisposition, lifestyle choices (e.g., diet, exercise), and environmental factors.
Conclusion
The balance between enough and too much pathogen exposure is delicate, and both extremes might contribute to an increased risk of inflammaging and age-related diseases. The preponderance of scientific evidence suggests that the adaptive immune system's limitations, especially as related to aging, do impact health outcomes. However, the relationship between pathogen exposure, immune system training, and inflammaging is complex and still under active investigation. Future research will likely continue to elucidate these intricate interactions for better understanding and potential interventions aimed at mitigating the effects of aging on the immune system.