Thymic output and functionality of the IL‐7/IL‐7 receptor system in centenarians: implications for the neolymphogenesis at the limit of human life

Aging Cell - Tập 5 Số 2 - Trang 167-175 - 2006
Milena Nasi1,2, Leonarda Troiano1,2, Enrico Lugli1, Marcello Pinti1, Roberta Ferraresi1, Elena Monterastelli1, Chiara Mussi3, Gianfranco Salvioli3, Claudio Franceschi4,5, Andrea Cossarizza1
1Department of Biomedical Sciences, Section of General Pathology, University of Modena and Reggio Emilia, School of Medicine, Via Campi 287, 41100 Modena, Italy
2Drs M. Nasi and L. Troiano have equally contributed to this work.
3Department of Internal Medicine, Section of Gerontology, University of Modena and Reggio Emilia School of Medicine, Ospedale Estense, Modena, Italy
4Department of Experimental Medicine, Section of Microbiology, University of Bologna School of Medicine, via San Giacomo 12, 40126 Bologna, Italy
5National Institute of Aging, INRCA, Ancona, Italy

Tóm tắt

SummaryDuring aging, the thymus undergoes a marked involution that is responsible for profound changes in the T‐cell compartment. To investigate the capacity of the thymus to produce new cells at the limit of human lifespan, we analyzed some basic mechanisms responsible for the renewal and maintenance of peripheral T lymphocytes in 44 centenarians. Thymic functionality was analyzed by the quantification of cells presenting the T‐cell receptor rearrangement excision circles (TREC). A new method based upon real‐time PCR was used, and we found that most centenarians (84%) had undetectable levels of TREC+ cells. Six‐color cytofluorimetric analysis revealed that centenarians had an extremely low number of naïve T cells; central memory and effector memory T cells were greatly increased, while terminally differentiated cells were as numerous as in young (aged 20–45) or middle‐aged (aged 58–62) donors. Interleukin (IL)‐7 and IL‐7 receptor α‐chain (CD127) levels were the same at all ages, as shown by ELISA, flow cytometry and real‐time PCR. However, IL‐7 plasma levels were higher in centenarian females than males. The presence of TREC+ cells and of very few naïve T lymphocytes suggests that in centenarians such cells could either derive from residues of thymic lymphopoietic islets, or even represent long‐living lymphocytes that have not yet encountered their antigen. IL‐7 could be one of the components responsible, among others, for the higher probability of reaching extreme ages typical of females.

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