Immunosenescence is the name given to the age-related decline in the capacity of the immune system to carry out its duties: defend against pathogens; destroy senescent and cancerous cells; participate in normal tissue maintenance. Inflammaging, a chronic inflammatory stage characteristic of aging that arises from maladaptive reactions to damage, the presence of senescent cells, and other causes, is considered by some researchers to be an aspect of immunosenescence, while others think of it as a distinct phenotype. Both immunosenescence and inflammaging are important contributions to degenerative aging. Infectious disease and cancer are far more dangerous for the old precisely because the immune system is diminished in capacity, while the chronic inflammation of aging contributes to all of the common age-related diseases.
The research and development communities are well aware of the damage done by immune aging, and many projects have aimed and continue to aim at producing therapies that can improve immune function in older individuals. Among the more promising approaches are the various ways to restore a more youthful capacity of hematopoietic stem cell populations to generate functional immune cells in the right proportions, or regrow the atrophied thymus to restore a youthful supply of new T cells of the adaptive immune system, or selectively destroy one or more of the small, dysfunctional subpopulations of immune cells that cause harm in the aging body. It is a very interesting, active area of development, but it remains to be seen as to how rapidly viable therapies can be introduced into widespread clinical use.
Immunosenescence: signaling pathways, diseases and therapeutic targets
Immunosenescence refers to the abnormal activation or dysfunction of the immune system as people age. Inflammaging is a typical pathological inflammatory state associated with immunosenescence and is characterized by excessive expression of proinflammatory cytokines in aged immune cells. Chronic inflammation contributes to a variety of age-related diseases, such as neurodegenerative disease, cancer, infectious disease, and autoimmune diseases. Although not fully understood, recent studies contribute greatly to uncovering the underlying mechanisms of immunosenescence at the molecular and cellular levels.
Immunosenescence is associated with dysregulated signaling pathways (e.g., overactivation of the NF-κB signaling pathway and downregulation of the melatonin signaling pathway) and abnormal immune cell responses with functional alterations and phenotypic shifts. These advances remarkably promote the development of countermeasures against immunosenescence for the treatment of age-related diseases. Some anti-immunosenescence treatments have already shown promising results in clinical trials.In this review, we discuss the molecular and cellular mechanisms of immunosenescence and summarize the critical role of immunosenescence in the pathogenesis of age-related diseases. Potential interventions to mitigate immunosenescence, including reshaping immune organs, targeting different immune cells or signaling pathways, and nutritional and lifestyle interventions, are summarized. Some treatment strategies have already launched into clinical trials. This study aims to provide a systematic and comprehensive introduction to the basic and clinical research progress of immunosenescence, thus accelerating research on immunosenescence in related diseases and promoting the development of targeted therapy.
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