How Aging Exacerbates Autoimmune Disease

Immunosenescence (noun): The gradual deterioration of the immune system, brought on by natural age advancement and marked by reduced immune cell function, increased inflammation, and impaired tolerance to the body’s own tissues.

As people age, their immune systems undergo a gradual decline known as immunosenescence. This age-related immune shift may raise the risk of developing autoimmune disease (AD).

A new review in Autoimmunity Reviews explores how immunosenescence contributes to the onset, progression, and severity of ADs such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, and type 1 diabetes. Aging alters how immune cells recognize self-antigens, impairs the removal of dying cells, and leads to the accumulation of pro-inflammatory, senescent immune cells that drive tissue damage.

The review also highlights how mitochondrial dysfunction and chronic inflammation—common features of aging—create a feedback loop that promotes further immune system decline. These age-associated changes not only increase the risk of autoimmunity but may also reduce the effectiveness of existing treatments.

Promising new therapies aim to target immunosenescence directly. These include senolytics (which clear senescent cells), senomorphics (which reduce harmful secretions), and approaches that may rejuvenate immune cells. Though still in early stages, such strategies could offer a novel way to manage or even prevent ADs in older adults.

As the global population ages, addressing immunosenescence may be key to reducing the growing burden of autoimmune disease.

Citation

Huifang Hu, et al (2025). Immunosenescence in autoimmune diseases, Autoimmunity Reviews, 103805, ISSN 1568-9972, https://doi.org/10.1016/j.autrev.2025.103805.