Daan Pieren

85 Compromised DNA repair promotes the accumulation of regulatory T cells REFERENCES 1. Goronzy, J. J. et al. Understanding immunosenescence to improve responses to vaccines . Nat. Immunol. 14, 428-436, doi:10.1038/ni.2588 (2013). 2. Akbar, A. N. et al. Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? Nat. Rev. Immunol. 11, 289-295, doi:10.1038/nri2959 (2011). 3. Pieren, D. K. J. et al. Response kinetics reveal novel features of ageing in murine T cells . Sci. Rep. 9, 5587, doi:10.1038/s41598-019-42120-1 (2019). 4. Lages, C. S. et al. Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation . J. Immunol. 181, 1835-1848 (2008). 5. Sharma, S. et al. High accumulation of T regulatory cells prevents the activation of immune responses in aged animals . J. Immunol. 177, 8348-8355 (2006). 6. Gregg, R. et al. The number of human peripheral blood CD4+ CD25high regulatory T cells increases with age . Clin. Exp. Immunol. 140, 540-546, doi:10.1111/j.1365-2249.2005.02798.x (2005). 7. Nishioka, T. et al. CD4+CD25+Foxp3+ T cells and CD4+CD25-Foxp3+ T cells in aged mice . J. Immunol. 176, 6586-6593, doi:10.4049/jimmunol.176.11.6586 (2006). 8. Elyahu, Y. et al. Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes . Sci Adv 5, eaaw8330, doi:10.1126/sciadv. aaw8330 (2019). 9. Garg, S. K. et al. Aging is associated with increased regulatory T-cell function . Aging Cell 13, 441-448, doi:10.1111/acel.12191 (2014). 10. Farber, D. L. et al. Human memory T cells: generation, compartmentalization and homeostasis . Nat. Rev. Immunol. 14, 24-35, doi:10.1038/nri3567 (2014). 11. Lopez-Otin, C. et al. The hallmarks of aging . Cell 153, 1194-1217, doi:10.1016/j.cell.2013.05.039 (2013). 12. Vermeij, W. P. et al. Genome Integrity in Aging: Human Syndromes, Mouse Models, and Therapeutic Options . Annu. Rev. Pharmacol. Toxicol. 56, 427-445, doi:10.1146/annurev- pharmtox-010814-124316 (2016). 13. Akbar, A. N. et al. Senescence of T Lymphocytes: Implications for Enhancing Human Immunity . Trends Immunol. 37, 866-876, doi:10.1016/j.it.2016.09.002 (2016). 14. Herbig, U. et al. Cellular senescence in aging primates . Science 311, 1257, doi:10.1126/ science.1122446 (2006). 15. Gorbunova, V. et al. Changes in DNA repair during aging . Nucleic Acids Res. 35, 7466- 7474, doi:10.1093/nar/gkm756 (2007). 16. Henson, S. M. et al. KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells . Blood 113, 6619-6628, doi:10.1182/blood-2009-01-199588 (2009). 17. Lanna, A. et al. The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells . Nat. Immunol. 15, 965-972, doi:10.1038/ ni.2981 (2014). 18. Gregg, S. Q. et al. Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease . DNA Repair (Amst) 10, 781-791, doi:10.1016/j.dnarep.2011.04.026 (2011). 19. Marteijn, J. A. et al. Understanding nucleotide excision repair and its roles in cancer and ageing . Nat. Rev. Mol. Cell Biol. 15, 465-481, doi:10.1038/nrm3822 (2014). 20. Niedernhofer, L. J. et al. A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis . Nature 444, 1038-1043, doi:10.1038/nature05456 (2006). 21. Vermeij, W. P. et al. Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice . Nature 537, 427-431, doi:10.1038/nature19329 (2016). 22. Robinson, A. R. et al. Spontaneous DNA damage to the nuclear genome promotes senescence, redox imbalance and aging . Redox Biol 17, 259-273, doi:10.1016/j. redox.2018.04.007 (2018). 23. Dolle, M. E. et al. Broad segmental progeroid changes in short-lived Ercc1(-/Delta7) mice . Pathobiol Aging Age Relat Dis 1, doi:10.3402/pba.v1i0.7219 (2011). 3