Tracing thymic output in older individuals

• Published in: Clinical and experimental immunology Vol. 161; no. 3; pp. 497 - 503
• Main Authors: Mitchell, W.A, Lang, P.O, Aspinall, R
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-09-2010; Blackwell Publishing Ltd; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Age; Aged; Aging; Analytical, structural and metabolic biochemistry; Biological and medical sciences; CD3 Complex - metabolism; elderly; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Gene Rearrangement, T-Lymphocyte - genetics; Humans; Leukocyte Count; Lymphocyte Count; Lymphocytes; Male; Middle Aged; mortality; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Reverse Transcriptase Polymerase Chain Reaction; T cell receptors; T-Lymphocytes - metabolism; thymic output; Thymus Gland - growth & development; Thymus Gland - metabolism; thymus TREC; Translational Studies; TREC assay; Human; Thymus gland; Mortality; thymus TREC; Biochemistry; TREC assay; Epidemiology; Assay; Traceability; T cell receptor excision circle; thymic output; Elderly; Age
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2010.04209.x

As a result of age-associated thymic atrophy, T cell production declines with age. Some studies suggest that production undergoes an exponential decline starting at birth, while others consider the decline to be in a biphasic manner with a rapid reduction in output occurring before middle age followed by a phase in which output declines at a regular, albeit much slower, rate. Both approaches provide estimations of the time of termination of thymic output, but on the basis of limited amounts of data. We have analysed blood from more than 200 individuals between the ages of 58 and 104 years to determine changes in thymic output using signal-joint T cell receptor excision circles (sjTREC)/T cells as our measure. To reduce any potential geographical or nutritional bias we have obtained samples from five different European countries. Our results reveal that while the absolute number of T cells per microlitre of blood does not change significantly across the age range we tested, the values of sjTREC per microlitre show wide variation and reveal an age-associated decline in thymic output. In addition we show gender differences, with notably higher thymic output in females than males at each decade. More importantly, we noted a significant decline in sjTREC/T cell levels in those more than 90 years of age in both males and females. Our results provide information about the potential end-point for thymic output and suggest that sjTREC analysis may be a biomarker of effective ageing.