Longitudinal studies are defining progressive alterations to the immune system associated with …

• Abstract
• Background
• Apoptosis
• Genetics
• In vivo correlates
• Mechanism
• Conclusion
• References

Biology Articles » Medicine » Age and immunity » Apoptosis

Apoptosis

- Age and immunity

Aging is associated with a paradox of increased autoimmunity, yet also with a state of immunodeficiency, with an increased frequency of infections and cancer. Among immune functions, a decline in T-cell functions during aging predominates. In aging, there is an increased production of TNF-α and decreased naive CD8+ T cells whereas memory CD8+T cells are increased, under the influence of CMV as discussed above. Sudhir Gupta (University of California) reported that naïve and central memory (TCM) CD8+ T cells are decreased in ageing, whereas the CD45RA- effector memory (TEM) and CD45RA+ effector memory (TEMRA) CD8+ T cells are increased. The hypothesis is that the alterations in naïve and CD8+T memory cells in ageing may be due to their differential sensitivity to apoptosis. Naive and TCM CD8+T cells from old donors are significantly more susceptible to TNF-α-induced apoptosis as compared to naïve and TCM from young subjects, whereas TEM and TEMRA CD8+ T cells are resistant to apoptosis in both young and aged subjects. Furthermore, in ageing, apoptosis in TCM CD8+ T cells, as defined by CCR7 or CD62L expression, was greater as compared to naive CD8+ T cells. It was also observed that the increased apoptosis in aged naive and TCM CD8+ T cells was associated with increased cleavage of both caspase-8 and caspase-3 as compared to young subjects [9,10]. This kind of increased apoptosis of naïve and central memory T cells may contribute to T cell immunodeficiency associated with human ageing. In contrast, abnormal phagocytosis of apoptotic body and failure to generate anti-inflammatory response by dendritic cells may explain the paradoxical increased inflammation associated with human ageing. Modulation of these processes may therefore also offer scope for intervention.