Inflamm‐aging: An Evolutionary Perspective on Immunosenescence

Annals of the New York Academy of Sciences - Tập 908 Số 1 - Trang 244-254 - 2000
Claudio Franceschi1,2, Massimiliano Bonafè1, Silvana Valensin1, Fabiola Olivieri2, María De Luca3, Enzo Ottaviani4, Giovanna De Benedictis3
1Department of Experimental Pathology, University of Bologna, Bologna, Italy
2Department of Gerontological Research, Italian National Research Center on Aging (INRCA), Ancona, Italy
3Department of Cell Biology, University of Calabria, Calabria, Italy
4Department of Animal Biology, University of Modena and Reggio Emilia, Modena, Italy

Tóm tắt

Abstract: In this paper we extend the “network theory of aging,” and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as “inflamm‐aging,” is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response. The rate of reaching the threshold of proinflammatory status over which diseases/disabilities ensue and the individual capacity to cope with and adapt to stressors are assumed to be complex traits with a genetic component. Finally, we argue that the persistence of inflammatory stimuli over time represents the biologic background (first hit) favoring the susceptibility to age‐related diseases/disabilities. A second hit (absence of robust gene variants and/or presence of frail gene variants) is likely necessary to develop overt organ‐specific age‐related diseases having an inflammatory pathogenesis, such as atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes. Following this perspective, several paradoxes of healthy centenarians (increase of plasma levels of inflammatory cytokines, acute phase proteins, and coagulation factors) are illustrated and explained. In conclusion, the beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.

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Annals of the New York Academy of Sciences

Tập 908 Số 1

244-254

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