Immunosenescence in autoimmune diseases

Mar 25, 2025Autoimmunity reviews

Aging of the Immune System in Autoimmune Diseases

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Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Autoimmune diseases (AIDs) are associated with various changes in the immune system due to aging and immunosenescence.

Immunosenescence involves multiple alterations in the immune system, including changes in self-antigens and lymphocyte function.
Aging may increase susceptibility to autoimmune diseases by narrowing the diversity of B and T cell receptors.
Senescent immune cells contribute to chronic inflammation and tissue damage in autoimmune diseases.
Mitochondrial dysfunction and metabolic imbalances may lead to an accumulation of senescent cells, driving immunosenescence.
Therapeutic strategies targeting immunosenescence in autoimmune diseases are still in early development.

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Autoimmune diseases (AIDs) are a group of disorders in which the immune system mistakenly attacks the body's own tissues, characterized by the loss of tolerance to self-antigens and destruction of tissues. Aging is a natural process of physiological decline that also alters the immune system, a condition known as immunosenescence. During immunosenescence, the immune system undergoes various changes, including modifications and antigenicity of self-antigens, abnormalities in the quantity, phenotype, and function of lymphocytes and antibodies, as well as a narrowing of the B and T cell receptor repertoire, changes that may increase susceptibility to AIDs. Additionally, senescent immune cells and the senescence-associated secretory phenotype (SASP) contribute to target organ involvement in AIDs, exacerbating chronic inflammation and tissue damage. Mitochondrial dysfunction and metabolic imbalances in AIDs lead to the accumulation of senescent cells, which act as upstream drivers of immunosenescence. In this review, we summarize the bidirectional relationship between AIDs and immunosenescence, as well as its potential mechanisms. Therapeutic approaches targeting immunosenescence in AIDs remain at an early stage. Strategies aimed at resetting or reversing the aging immune system are expected to become a novel direction in the future.

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Immunosenescence in autoimmune diseases

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