G. Colonna-Romano, G. Candore, A. Aquino, M. Bulati, S. Vitello, D. Lio, I.M. Rea, C. Caruso

Ageing is an inexorable intrinsic process that affects all cells, tissues, organs and organisms. In fact, humans, as well as the other animals, are designed as a compromise to guarantee optimal survival until the time of reproduction based on natural selection that is effective until that age, so the post-reproductive physiology of an organism (i.e., ageing) is an epigenetic and pleiotropic manifestation of the optimisation for early fitness. The progressive decrease in physiological capacity and the reduced ability to respond to stresses lead to increased susceptibility and vulnerability to diseases. Thus, mortality due to all causes increases exponentially with ageing. Improvement of hygiene, preventive and curative medicine as well as socio-economic developments have led to an increase of the human mean life expectancy that allows ever larger proportions of the population to reach an age that is far beyond that of the reproductive phase, but the maximum lifespan potential (MSLP) has remained constant. Besides, MLSP appears to be species specific, implying a significant genetic component to the rate of ageing. Evolutionary theory and empirical evidence suggest that ageing is a process of gradual accumulation of damage in cells and tissues of the body. Thus, genes implied in ageing and longevity are implied in the network of cell maintenance systems, including immune system genes. In fact, longevity may be correlated with optimal functioning of the immune system and the ageing of immune system, immunosenescence, is the consequence of the continuous attrition caused by chronic antigenic overload. Some of the most important characteristics of adaptive immunity in ageing are compatible with this assumption. Concomitantly, the antigenic load results in the progressive generation of inflammatory responses involved in age-related diseases. Most of the parameters affected by immunosenescence appear to be under genetic control, and research is addressing this point. So, immunosenescence fits with basic assumptions of evolutionary theories of ageing, such as antagonistic pleiotropy. In fact, the immune system, by neutralizing infectious agents, plays a beneficial role until the time of the reproductions and parental cares, but, by determining a chronic inflammation, can play a detrimental one late in life, in a period largely not foreseen by evolution.

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Immune Response