Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging

被引:287
作者
Thomas, Rachel [1 ]
Wang, Weikan [1 ]
Su, Dong-Ming [2 ]
机构
[1] Grad Sch Biomed Sci, Cell Biol Immunol & Microbiol Grad Program, Ft Worth, TX 76107 USA
[2] Univ North Texas Hlth Sci Ctr, Dept Microbiol Immunol & Genet, Ft Worth, TX 76107 USA
关键词
Thymic aging; Age-related thymic involution; Central tolerance; Negative selection and regulatory T (Treg) cell generation; Immunosenescence and inflammaging; Rejuvenation; REGULATORY T-CELLS; PERIPHERAL-BLOOD; BONE-MARROW; CELLULAR SENESCENCE; NEGATIVE SELECTION; GROWTH-HORMONE; CHOROID-PLEXUS; IMMUNE-SYSTEM; STEM-CELLS; LIFE-SPAN;
D O I
10.1186/s12979-020-0173-8
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Immune system aging is characterized by the paradox of immunosenescence (insufficiency) and inflammaging (over-reaction), which incorporate two sides of the same coin, resulting in immune disorder. Immunosenescence refers to disruption in the structural architecture of immune organs and dysfunction in immune responses, resulting from both aged innate and adaptive immunity. Inflammaging, described as a chronic, sterile, systemic inflammatory condition associated with advanced age, is mainly attributed to somatic cellular senescence-associated secretory phenotype (SASP) and age-related autoimmune predisposition. However, the inability to reduce senescent somatic cells (SSCs), because of immunosenescence, exacerbates inflammaging. Age-related adaptive immune system deviations, particularly altered T cell function, are derived from age-related thymic atrophy or involution, a hallmark of thymic aging. Recently, there have been major developments in understanding how age-related thymic involution contributes to inflammaging and immunosenescence at the cellular and molecular levels, including genetic and epigenetic regulation, as well as developments of many potential rejuvenation strategies. Herein, we discuss the research progress uncovering how age-related thymic involution contributes to immunosenescence and inflammaging, as well as their intersection. We also describe how T cell adaptive immunity mediates inflammaging and plays a crucial role in the progression of age-related neurological and cardiovascular diseases, as well as cancer. We then briefly outline the underlying cellular and molecular mechanisms of age-related thymic involution, and finally summarize potential rejuvenation strategies to restore aged thymic function.
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页数:17
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