Targeting immune dysfunction in aging

• Published in: Ageing research reviews 2021-09, Vol.70, p.101410-101410, Article 101410
• Main Authors: Borgoni, Simone, Kudryashova, Ksenia S., Burka, Ksenia, de Magalhães, João Pedro
• Format: Article
• Language: English
• Subjects: Anti-aging; Geroscience; Healthy longevity; Immune system; Immunosenescence; Inflammation
• ISSN: 1568-1637; 1872-9649
• DOI: 10.1016/j.arr.2021.101410

•The immune system becomes highly dysfunctional during aging and new anti-aging therapeutic approaches targeting the immune system are being proposed at a growing pace, with many of them showing promising pre-clinical results.•Due to its interconnection with all other systems in the body, its relevance for homeostasis maintenance and the primary role in fighting infections and cancer, the immune system represents the ideal target to comprehensively address many hallmarks of aging.•Successful immune targeting approaches are directed either against specific cell types (hematopoietic stem cells, T cells, macrophages) or processes (immune metabolism, immune senescence).•Current promising immune-targeting strategies involve: rejuvenation of aged immune tissues or cells, immunosuppressive strategies to tune down dysregulated populations that promote inflammaging and stimulatory strategies to re-activate, eliminate, or replace senescent cells.•Targeting multiple components of the immune system at once requires an extremely balanced approach to avoid undesired side effects. Human aging is a multifactorial phenomenon that affects numerous organ systems and cellular processes, with the immune system being one of the most dysregulated. Immunosenescence, the gradual deterioration of the immune system, and inflammaging, a chronic inflammatory state that persists in the elderly, are among the plethora of immune changes that occur during aging. Almost all populations of immune cells change with age in terms of numbers and/or activity. These alterations are in general highly detrimental, resulting in an increased susceptibility to infections, reduced healing abilities, and altered homeostasis that promote the emergence of age-associated diseases such as cancer, diabetes, and other diseases associated with inflammation. Thanks to recent developments, several strategies have been proposed to target central immunological processes or specific immune subpopulations affected by aging. These therapeutic approaches could soon be applied in the clinic to slow down or even reverse specific age-induced immune changes in order to rejuvenate the immune system and prevent or reduce the impact of various diseases. Due to its systemic nature and interconnection with all the other systems in the body, the immune system is an attractive target for aging intervention because relatively targeted modifications to a small set of cells have the potential to improve the health of multiple organ