Low Thymic Function Correlates with a Twofold Risk of Mortality in Old People

The thymus is a small organ in which thymocytes mature into T cells of the adaptive immune system. Active thymic tissue atrophies with age, a process that appears to be accelerated by the usual suspects such as a poor lifestyle and chronic inflammation. As a result, the supply of new T cells diminishes, and the adaptive immune system becomes ever less functional and ever more inflammatory as a result, packed with exhausted, malfunctioning, and senescent cells.

Researchers here report on a study in which they assessed the pace at which new T cells left the thymus in a population of older people. They found that the lowest quartile, those with the lowest production of new T cells, exhibited a twofold increase in mortality risk in comparison to those in the normal range for their age. The immune system is important to health, but this likely also reflects a higher burden of age-related damage that encourages greater thymic atrophy.

Immunosenescence is a complex process characterized by an age-related remodelling of the immune system. The prominent effects of the immunosenescence process is the thymic involution and, consequently, the decreased numbers and functions of T cells. Since thymic involution results in a collapse of the T-cell receptor (TCR) repertoire, a reliable biomarker of its activity is represented by the quantification of signal joint T-cell receptor rearrangement excision circles (sjTRECs) levels. Although it is reasonable to think that thymic function could play a crucial role on elderly survival, only a few studies investigated the relationship between an accurate measurement of human thymic function and survival at old ages.

By quantifying the amount sjTRECs by real-time polymerase chain reaction (PCR), the decrease in thymic output in 241 nursing home residents was evaluated to investigate the relationship between thymic function and survival at old ages. The mean age of these patients was 78.4 years. We found that low sjTREC levels were associated with a significant increased risk of mortality at older ages. Nursing home residents with lower sjTREC exhibit a near 2-fold increase in mortality risk compared to those with sjTREC levels in a normal range.

In conclusion, thymic function failure is an independent predictor of mortality among elderly nursing home residents. sjTREC represents a biomarker of effective ageing as its blood levels could anticipate individuals at high risk of negative health outcomes. The identification of these subjects is crucial to manage older people's immune function and resilience, such as, for instance, to plan more efficient vaccine campaigns in older populations.

Link: https://doi.org/10.1186/s12979-023-00340-0

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