Tracing thymic output in older individuals

Abstract

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.

Fig. 1

Age-related changes in T cell receptor excision circles (TRECs) per 10⁵ T cells. Each dot represents an individual measurement.

Fig. 2

Number of leucocytes (□) and CD3⁺ T cells (○) per microlitre of blood at different ages.

Fig. 3

Age-related changes in T cell receptor excision circles (TRECs) per 10⁵ T cells according to gender.

Fig. 4

Signal-joint T cell receptor excision circles (sjTRECs) as a biomarker of immunosenescence. Annotated diagram of the age-related changes observed in sjTREC measurements. The dashed horizontal grey line indicates the median sjTREC per 10⁵ T cells in the sample population. The dashed vertical grey line indicates the average life expectancy across the study population (79·0 years). UL, LL, UR, LR refer to the different quadrants formed by the bisection of the data horizontal and vertical lines.