Trends in Immunology
ReviewImmune senescence special issue. Free access sponsored by the National Institutes of HealthAn evolutionary perspective on the mechanisms of immunosenescence
Section snippets
Introduction: immunity and ageing
Potential pathogens—viral, bacterial, fungal, macroparasite and dysfunctional host cells—present a major threat to survival, and the innate and adaptive immune systems have evolved a series of defence networks to protect the individual from such harmful agents. These systems are not without fault, however, and with increasing age, problems arise in functional activity. There is clear evidence of an age-related decline in effectiveness of the immune systems of vertebrates and some invertebrates,
Immunosenescence between and within species
Invertebrates also appear to exhibit immunosenescence, for instance, bacteria tend to overcome the immune systems of older Caenorhabditis elegans, and their proliferation in the gut is the most frequent cause of death [26]. Similarly, Drosophila show a proinflammatory status with increasing age [27] and have a reduced capacity to produce antimicrobial peptides in response to infections [28], although, interestingly, they are reported to have a higher titre with age due to the additional
Age-associated thymic involution
One of the most universally recognized changes of the ageing vertebrate immune system is the dramatic regression, or involution, of the thymus, the major organ responsible for T-cell development [42]. The features of age-related thymic involution include a reduction in tissue mass, loss of tissue structure and abnormal architecture and a decline in thymocyte numbers, leading to a reduction in naïve T-cell output. It is the age-associated decline in naïve T-cell output that many have argued
Factors regulating age-associated thymic involution
Although understanding the physiological consequences of involution might provide clues as to the targets on which evolutionary selection could act, identifying molecular events (i.e. changes in the expression or function of genes or pathways) that drive involution might be informative in understanding how involution arose during vertebrate evolution. In this regard, identifying the cell type(s) that are the driving force of involution is key. The contribution of different potential mechanisms
Physiological cost of immunity
The energetic costs of immunity include the cost of developing the systems; the cost of maintaining the systems and the cost of combating bouts of infection [86]. The development of the innate system does not impose a particularly high burden. By contrast, the adaptive system is characterised by the large cost incurred early in life by the huge number of cells that must be produced, the majority of which are simply discarded through positive and negative selection in the thymus and bone marrow.
Conclusions, evolutionary and systems perspective
The force of natural selection declines with age, leading to a particular value being placed on survival to maturity and on reproductive output thereafter. An ability to mount a strong inflammatory response early in life and the finely tuned repression of the immune response to accommodate successful reproduction are clearly in support of this. The disposable soma theory is of broad applicability: investment in the immune system needs to be sufficient to ensure survival in the prevailing
Acknowledgements
Part of this work (D.P.S.) was supported by, and carried out within, the EU-funded Network of Excellence Lifespan (FP6 036894). D.A. was supported by a grant from Research into Ageing and N.R.M. by a grant from NIH/NIAID (AI055001).
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