**6. Conclusion**

In conclusion, age-related thymic atrophy is a dynamic process beginning early in life that shapes T cell development and the establishment of central T cell tolerance. There is substantial clinical significance in further exploring the underlying mechanisms of its effects on the various subsets of T cells developed in the atrophied thymus, namely Treg and Tcon cells. Also, continued investigation into potential avenues of thymic rejuvenation are striving to reverse the adverse effects of age-related thymic atrophy on the aged T cell immune system, since increased self-reactive T cells are observed with age, contributing to inflammaging. Moreover, there are numerous areas still to explore in this field with far-reaching applications.

## **Acknowledgements**

We would like to thank Dr. Rance Berg (Department of Microbiology, Immunology and Genetics, UNTHSC) for critical reading of this manuscript.

## **Conflict of interest**

The authors have no conflict of interest.

#### **Funding**

Supported by NIH/NIAID grant R01AI121147 to D-M. S. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

**59**

**Author details**

Rachel Thomas1

Fort Worth, Texas, USA

provided the original work is properly cited.

and Dong-Ming Su<sup>2</sup>

Texas Health Science Center, Fort Worth, Texas, USA

\*Address all correspondence to: dongming.su@unthsc.edu

\*

of Biomedical Sciences, University of North Texas Health Science Center,

1 Cell Biology, Immunology, and Microbiology Graduate Program, Graduate School

2 Department of Microbiology, Immunology, and Genetics, University of North

*Age-Related Thymic Atrophy: Mechanisms and Outcomes DOI: http://dx.doi.org/10.5772/intechopen.86412*

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Age-Related Thymic Atrophy: Mechanisms and Outcomes DOI: http://dx.doi.org/10.5772/intechopen.86412*

*Thymus*

**6. Conclusion**

**Acknowledgements**

**Conflict of interest**

**Funding**

the manuscript.

The authors have no conflict of interest.

with the normal thymus at endpoint (4 weeks after engraftment). Additionally,

The overarching conclusions taken from these cytokine, cellular, genetic, or epigenetically-based rejuvenation strategies are that FoxN1 expression is a key target for rejuvenating TECs, resulting in a more functional thymus able to produce normal T cells. However, we need to recognize that any rejuvenation therapy has its pitfalls. For example, intrathymic injection of newborn TECs can rejuvenate middle-aged thymus [114], but the source of newborn TECs is limited and may not be ideal as a translational therapy. Additionally, generation of an ectopic *de novo* thymus under the kidney capsule [115] can generate naïve T cells, but this does not remedy the increased self-reactive T cells released by the original atrophied thymus remaining in the host. Also, the use of cytokines may help revitalize the thymus, but as a systemic therapy could present various detrimental side-effects. Therefore,

typical thymus microstructure was observed in these grafts [115].

further studies to develop practical and effective therapies are necessary.

In conclusion, age-related thymic atrophy is a dynamic process beginning early in life that shapes T cell development and the establishment of central T cell tolerance. There is substantial clinical significance in further exploring the underlying mechanisms of its effects on the various subsets of T cells developed in the atrophied thymus, namely Treg and Tcon cells. Also, continued investigation into potential avenues of thymic rejuvenation are striving to reverse the adverse effects of age-related thymic atrophy on the aged T cell immune system, since increased self-reactive T cells are observed with age, contributing to inflammaging. Moreover, there are numerous areas still to explore in this field with far-reaching applications.

We would like to thank Dr. Rance Berg (Department of Microbiology, Immunology and Genetics, UNTHSC) for critical reading of this manuscript.

Supported by NIH/NIAID grant R01AI121147 to D-M. S. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of

**58**
