Immunosenescence: molecular mechanisms and diseases

• Published in: Signal transduction and targeted therapy Vol. 8; no. 1; p. 200
• Main Authors: Liu, Zaoqu, Liang, Qimeng, Ren, Yuqing, Guo, Chunguang, Ge, Xiaoyong, Wang, Libo, Cheng, Quan, Luo, Peng, Zhang, Yi, Han, Xinwei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.05.2023; Nature Publishing Group
• Subjects: 631/67/327; 631/80/509; Aging; Cancer immunotherapy; Cancer Research; Cell Biology; Cellular Senescence - genetics; Clinical trials; Epigenetics; Geriatrics; Humans; Immunosenescence; Immunosenescence - physiology; Immunosuppressive agents; Inflammation; Internal Medicine; Lymphocytes T; Medicine; Medicine & Public Health; Molecular modelling; Neoplasms - genetics; Neoplasms - therapy; Oncology; Pathology; Phenotypes; Review; Review Article; Risk factors; Senescence; T-Lymphocytes; Thymic involution; Thymus; Vaccination
• ISSN: 2059-3635; 2095-9907; 2059-3635
• DOI: 10.1038/s41392-023-01451-2

Infection susceptibility, poor vaccination efficacy, age-related disease onset, and neoplasms are linked to innate and adaptive immune dysfunction that accompanies aging (known as immunosenescence). During aging, organisms tend to develop a characteristic inflammatory state that expresses high levels of pro-inflammatory markers, termed inflammaging. This chronic inflammation is a typical phenomenon linked to immunosenescence and it is considered the major risk factor for age-related diseases. Thymic involution, naïve/memory cell ratio imbalance, dysregulated metabolism, and epigenetic alterations are striking features of immunosenescence. Disturbed T-cell pools and chronic antigen stimulation mediate premature senescence of immune cells, and senescent immune cells develop a proinflammatory senescence-associated secretory phenotype that exacerbates inflammaging. Although the underlying molecular mechanisms remain to be addressed, it is well documented that senescent T cells and inflammaging might be major driving forces in immunosenescence. Potential counteractive measures will be discussed, including intervention of cellular senescence and metabolic-epigenetic axes to mitigate immunosenescence. In recent years, immunosenescence has attracted increasing attention for its role in tumor development. As a result of the limited participation of elderly patients, the impact of immunosenescence on cancer immunotherapy is unclear. Despite some surprising results from clinical trials and drugs, it is necessary to investigate the role of immunosenescence in cancer and other age-related diseases.