Immune Alterations with Aging: Mechanisms and Intervention Strategies

Abstract

Aging is the result of a complex interplay of physical, environmental, and social factors, leading to an increased prevalence of chronic age-related diseases that burden health and social care systems. As the global population ages, it is crucial to understand the aged immune system, which undergoes declines in both innate and adaptive immunity. This immune decline exacerbates the aging process, creating a feedback loop that accelerates the onset of diseases, including infectious diseases, autoimmune disorders, and cancer. Intervention strategies, including dietary adjustments, pharmacological treatments, and immunomodulatory therapies, represent promising approaches to counteract immunosenescence. These interventions aim to enhance immune function by improving the activity and interactions of aging-affected immune cells, or by modulating inflammatory responses through the suppression of excessive cytokine secretion and inflammatory pathway activation. Such strategies have the potential to restore immune homeostasis and mitigate age-related inflammation, thus reducing the risk of chronic diseases linked to aging. In summary, this review provides insights into the effects and underlying mechanisms of immunosenescence, as well as its potential interventions, with particular emphasis on the relationship between aging, immunity, and nutritional factors.

Keywords: aging; diet intervention; immune system; immunosenescence; immunotherapy.

Figure 1

The effects of aging on different immune cells in the intrinsic and adaptive immune systems. Changes in the immune system involve the decline of both innate and adaptive immunity, along with the development of the senescence-associated secretory phenotype (SASP). Aging leads to alterations in the number and function of immune cells, with the adaptive immune system being more significantly affected. For innate immunity, the percentages of pro-inflammatory macrophages (M1) and type 1 DCs increase during aging; the phagocytosis and cytokine secretion decrease in both DCs and neutrophils; the cytotoxicity of NKs also decline in old individuals. For adaptive immunity, both T cell and B cell populations decline in the elderly, with a concomitant reduction in TCR diversity and impaired antibody production. The red upward arrow indicates an increase, the green downward arrow indicates a decrease, and “—” represents no change.

Figure 2

Multiple factors contribute to the aging of the immune system. These include thymic involution, inflammatory damage, DNA damage, telomere shortening, and mitochondrial dysfunction. The overall oxidation level increases with the higher level of inflammatory cytokines, activating pathways like NF-κB. The release of mtDNA from dysregulated mitochondria triggers the cGAS-STING pathway. The interaction of multiple pathways aggravates SASP. The red upward arrow indicates an increase, the green downward arrow indicates a decrease.

Figure 3

Aging affects the immune system and leads to age-related diseases. During aging, the likelihood of infection increases due to the deterioration of the immune system. This process is characterized by an enhanced inflammatory response, reduced T cell diversity, and diminished antibody production, which collectively increase vulnerability to bacterial and viral infections. Additionally, as aging progresses, the immune system’s tolerance to self-antigens decreases, and immune cell infiltration occurs, contributing to the development of autoimmune diseases. Furthermore, compromised immune functions during aging provide a conducive environment for cancer development. The red upward arrow indicates an increase, the green downward arrow indicates a decrease.

Figure 4

Dietary interventions, including proteins, carbohydrates, fats, vitamins, minerals, probiotics, and prebiotics, have significant effects on immune system function. Proteins enhance immunity by influencing T cell survival and differentiation, as well as by promoting B cell antibody production. Carbohydrates can strengthen innate immune responses and reduce cell apoptosis. The immunomodulatory effects of fats are primarily mediated by fatty acids, which enhance T cell antigen presentation, B cell proliferation, antibody production, and the antimicrobial activity of immune proteins. Vitamins regulate thymic and bone marrow homeostasis, enhancing the function of macrophages, dendritic cells, and T cells. Minerals play an essential role in modulating the production of immune regulators and antibodies. Probiotics and prebiotics modulate gut immunity by influencing the gut microbiota, reducing inflammation, and enhancing the function of various immune cells. The red upward arrow indicates an increase, the green downward arrow indicates a decrease.

Figure 5

Various potential interventions and strategies that can improve aging immune functions. (1) Lifestyle interventions include adjustments in diet, exercise, and sleep patterns. (2) Pharmacological interventions encompass anti-inflammatory drugs, activators of specific molecules, and inhibitors of certain pro-aging signaling pathways. (3) Immunotherapeutic approaches involve the transplantation of immune cells, CAR-T technologies, and hematopoietic stem cell transplants. The red upward arrow indicates an increase, the green downward arrow indicates a decrease.