Ageing of the Immune System: Intrinsic or Extrinsic?

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Advance ageing correlates with a reduced ability to mount an effective immune response. Termed, immunosenescence, the precise mechanisms have not been fully elucidated although extensive analyses suggest intrinsic defects within immune cells are potentially involved. However, a picture is now emerging that the stromal microenvironment within lymphoid organs also contributes significantly to the age-associated decline of immune function. For instance, we and others have observed that thymic involution is associated with dramatic alterations in the thymic architecture of older animals. Equally, we have identified that the spleen, also undergoes age-associated changes. Environmental factors such as nutrition during fetal/early life can influence long-term health, a concept termed developmental programming. Initial studies showed effects on metabolic health but more recent studies have demonstrated effects on parameters such as lifespan and immunity. Our studies have shown that conditions that produced short-lived animals exhibit accelerated ageing of the thymic and splenic architecture and showed enhanced serum levels of pro-inflammatory cytokines; TNF-alpha and IL-1beta in adulthood. In contrast, conditions that produced long-lived animals demonstrated delayed thymic involution, reduced splenic deterioration, together with a higher naïve:memory ratio of splenic T cells. Overall our studies revealed that these age-dependent changes in the stromal niche could potentially contribute to the age-related deficiencies in functional immunity and that pathways involved in controlling/establishing ageing and longevity, in early life, are perhaps intimately associated with the generation of immunosenescence.