TY - JOUR T1 - T cell immunity does not age in a long-lived rodent species JF - bioRxiv DO - 10.1101/259374 SP - 259374 AU - M. Izraelson AU - T.O. Nakonechnaya AU - A.N. Davydov AU - M.A Dronina AU - D.A. Miskevich AU - I.Z. Mamedov AU - L.N. Barbashova AU - M. Shugay AU - D.A. Bolotin AU - D.B. Staroverov AU - E.Y. Kondratyuk AU - E.A. Bogdanova AU - S. Lukyanov AU - I. Shams AU - O.V Britanova AU - D.M. Chudakov Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/02/02/259374.abstract N2 - Numerous studies have demonstrated that the percentage of naïve T cells and diversity of T cell receptor (TCR) repertoire decrease with age, with some findings likewise suggesting that increased repertoire diversity may be associated with longer lifespan and healthy aging. In this work, we have analyzed peripheral TCR diversity from humans, mice, and blind mole-rats (Spalax spp.)—long-lived, hypoxia- and cancer-tolerant rodents. We employed a quantitative approach to TCR repertoire profiling based on 5’RACE with unique molecular identifiers (UMI) to achieve accurate comparison of repertoire diversity, which also required development of specific wet lab protocol and TCR gene reference for Spalax. Our direct comparison reveals a striking phenomenon. Whereas TCR diversity of mice and humans decreases with age, resulting primarily from the shrinkage of the naive T cell pool, Spalax TCR diversity remains stable even for the animals that reach extreme old age (15–17 years). This indicates that T cell immunity does not meaningfully age in long-lived rodents, at least in terms of the classical understanding of immunosenescence, which is associated with the accumulation of large numbers of memory clones. We suggest that the extraordinary longevity of Spalax may be attributable at least in part to the distinctive organization of their T cell immunity. Our findings should therefore encourage a close re-examination of the contribution of immunosenescence to life span in mammals. ER -