Immunosenescence and the Aging Immune System
Aging
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The immune system is a vast and intricate network. Seven percent of the entire human genome is composed of immune-specific genes. This complex system has important functional and maintenance roles that involve clearing out foreign pathogens and sweeping away dead or dysfunctional cells. As do most human systems, the immune system experiences degradation with age. This degradation in aging populations results in inadequate immune responses to invading pathogens, self-antigens, undesirable/malfunctioning cells, and even to vaccines.
“Furthermore, the aged immune system elicits an inadequate response to vaccines, leaving the elderly susceptible to pathogens despite being vaccinated against them [29, 30]. This is especially poignant in the wake of an ongoing pandemic where the mortality rate is disproportionately high in the elderly [31].”
Researchers from the University of Florida authored a well-written review article (with exceptionally vivid figures and illustrations) exploring a potential cause of the aging immune system. They believe therapies that could target this cause may stave off age-related diseases and improve our quality of life as we age. The paper was published by Aging (Aging-US) in 2021, and entitled, “Cellular senescence in lymphoid organs and immunosenescence.”
Cellular Senescence
A mechanism that researchers believe may be responsible for many dysfunctions associated with aging is cellular senescence—the cessation of cell division. In youth, cellular senescence is a beneficial, protective process that aids in promoting optimal wound healing, preventing cancer, and mitigating the progression of fibrosis. As we age, however, the accumulation of senescent cells (SnCs) and their senescence-associated secretory phenotype (SASP) secretions cause instability and dysfunction.
“Both SnCs and SASP factors have been implicated in many of the age-related deteriorations, dysfunctions and diseases including but not limited to frailty, hypertrophy of tissue, stem-cell exhaustion, bystander effect mediated senescent cell accumulation, and cancer [51–63].”
The deleterious onset of cellular senescence with age impacts numerous systemic functions, including the immune system. The specific process of immune dysfunction that occurs with age is referred to as immunosenescence. Authors of this review article discuss interactions between cellular senescence and the immune system. Their focus is on the accumulation of SnCs within lymphoid organs in the aging body.
“With many more possible domains of interaction between cellular senescence and the immune system, as seen in (Figure 1), this review will discuss literature that states or suggests the presence of this interaction, with a focus on cellular senescence in the lymphoid organs, and raises questions that need to be answered to strengthen the foundation of the role of cellular senescence in immunosenescence.”
Immunosenescence in Lymphoid Organs
“The interactions between SnCs and the immune system run in both directions, with the immune system surveilling and clearing the SnCs; while the SnCs frequently impede the function, and in some contexts, generation of immune cells.”
Available research literature shows (finely detailed by the authors in this review article) that aging lymphoid organs—composed of the thymus, spleen, lymph nodes, bone marrow, and mucosa associated lymphoid tissue—all display various age-related changes that stem from immunosenescence. The researchers wrote that these senescence-associated changes occurring across the immune system are so numerous and pleiotropic, that to individually address each issue would be “ill-advised.”
“A more feasible and effective way to deal with immunosenescence would be to tackle the fundamental aspects of aging that drive immunosenescence.”
Conclusion
In the conclusion of their review, the authors provide a number of thought-provoking questions about cellular senescence that have yet to be answered. Studies that may attempt to answer these questions could produce intriguing, and potentially life-changing, future research.
“Ultimately, gaining a deeper understanding of the interaction between cellular senescence and immunosenescence will help in the development of improved therapeutics that will aid in the conservation of our vitality as we age.”
Click here to read the full review article, published by Aging.
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