CoChat
Sign Up
Cited by 473T-cell and B-cell ImmunologyTelomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model Organisms

The DOI matches its Crossref record; 260 of the 260 references it cites were found in a registry or an index.

Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging

Open access
Thomas, Rachel, Wang, Weikan, Su, Dong-Ming·2020·Immunity & Ageing
DOI 10.1186/s12979-020-0173-8PMC PMC6971920
Open this paper in CoChat — free accountOpen PDF

Abstract

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s12979-020-0173-8

Cites

260 of 260 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig. 1 Intersection of immunosenescence and inflammaging is associated with age-related thymic involution. The aged, involuted thymus exhibits ineffective central tolerance and declined thymopoiesis. The ineffective central tolerance includes (1) impaired negative selection, which leads to the increased output of self-reactive T cells that attack self-tissues/organs, and (2) imbalanced generation of tTreg TCR repertoire, which fails to sufficiently suppress self-reactive T cell–mediated autoimmune responses. Autoimmune responses lead to tissue damage and thus cause chronic inflammation, which is one of the contributors to inflammaging. Reduced thymopoiesis leads to decreased output of naïve T cells for the clearance of senescent somatic cells (SSCs) and the expansion of oligo-clonal T cells in the aged periphery lack sufficient clearance capacity, which allows for SSC accumulation. SSCs are an important source of SASP, another contributor to inflammaging
Fig. 1 Intersection of immunosenescence and inflammaging is associated with age-related thymic involution. The aged, involuted thymus exhibits ineffective central tolerance and declined thymopoiesis. The ineffective central tolerance includes (1) impaired negative selection, which leads to the increased output of self-reactive T cells that attack self-tissues/organs, and (2) imbalanced generation of tTreg TCR repertoire, which fails to sufficiently suppress self-reactive T cell–mediated autoimmune responses. Autoimmune responses lead to tissue damage and thus cause chronic inflammation, which is one of the contributors to inflammaging. Reduced thymopoiesis leads to decreased output of naïve T cells for the clearance of senescent somatic cells (SSCs) and the expansion of oligo-clonal T cells in the aged periphery lack sufficient clearance capacity, which allows for SSC accumulation. SSCs are an important source of SASP, another contributor to inflammagingCC BY · PubMed Central
Fig. 2 TCR signaling strength decides self-reactive CD4sp T clone fates. Interaction between MHC-II/self peptide complex on mTEC and self-reactive TCR on CD4sp thymocyte produces three types of signaling strength: (1) a strong signal leads to negative selection, resulting in thymocyte depletion; (2) an intermediate signal leads to tTreg generation; (3) a weak signal results in thymocyte differentiation into T conventional (Tcon) cells. We hypothesize that age-related thymic involution shifts signaling strength from strong to intermediate and relatively enhances polyclonal tTreg generation (black arrow—a) ; while in some cases, antigen-specific interactions exhibit an even weaker signal, resulting in diminished antigen-specific tTreg cells and increased antigen-specific Tcon cells (black arrow—b)
Fig. 2 TCR signaling strength decides self-reactive CD4sp T clone fates. Interaction between MHC-II/self peptide complex on mTEC and self-reactive TCR on CD4sp thymocyte produces three types of signaling strength: (1) a strong signal leads to negative selection, resulting in thymocyte depletion; (2) an intermediate signal leads to tTreg generation; (3) a weak signal results in thymocyte differentiation into T conventional (Tcon) cells. We hypothesize that age-related thymic involution shifts signaling strength from strong to intermediate and relatively enhances polyclonal tTreg generation (black arrow—a) ; while in some cases, antigen-specific interactions exhibit an even weaker signal, resulting in diminished antigen-specific tTreg cells and increased antigen-specific Tcon cells (black arrow—b)CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 260 references

Cited by

Sorted by citations

Items 401–473 of 473

Related

See all

Metadata

Authors
Thomas, R., Wang, W., & Su, D.-M.
Affiliations
University of North Texas Health Science Center (US)
Corresponding author
Su, Dong-Ming
ORCID
Venue
Immunity & Ageing
Publisher
Springer Science and Business Media LLC
Published
2020-01-20
Volume
17
Issue
1
Pages
2-2
ISSN
1742-4933 (ISSN-L)
DOI
10.1186/s12979-020-0173-8
PMC
PMC6971920
OpenAlex
W3010019019
Cited by
442
References
260
Citations by year
2026: 69 · 2025: 76 · 2024: 84 · 2023: 64 · 2022: 51 · 2021: 58 · 2020: 40
FWCI
5.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity & Ageing (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R01AI121147)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
thymic involution, immunosenescence, inflammaging, thymic aging, T cell function, cellular senescence, senescence-associated secretory phenotype, epigenetic regulation, age-related neurological diseases, age-related cardiovascular disease

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review