Inflamm‐aging is a relatively new terminology used to describe the age‐related increase in the systemic pro‐inflammatory status of humans. Here, we represent inflamm‐aging as a breakdown in the multi‐shell cytokine network, in which stem cells and stromal fibroblasts (referred to as the stem cell niche) become pro‐inflammatory cytokine over‐expressing cells due to the accumulation of DNA damage. Inflamm‐aging self‐propagates owing to the capability of pro‐inflammatory cytokines to ignite the DNA‐damage response in other cells surrounding DNA‐damaged cells. Macrophages, the major cellular (...) player in inflamm‐aging, amplify the phenomenon, by broadcasting pro‐inflammatory signals at both local and systemic levels. On the basis of this, we propose that inflamm‐aging is a major contributor to the increase in cancer incidence and progression in aged people. Breast cancer will be presented as a paradigmatic example for this relationship. (shrink)

Ecological Immunology assumes that immunological defenses must be minimized in terms of cost (energy expenditure). To reach this goal, a complex and still largely unexplored strategy has evolved to assure survival. From invertebrates to vertebrates, an integrated immune–neuroendocrine response appears to be crucial for the hierarchical redistribution of resources within the body according to the specific ecological demands. Thus, on the basis of experimental data on the intimate relationship between stress and immune responses that has been maintained during evolution, we (...) argue that a broader perspective based on the integration of immune and neuroendocrine responses should be adopted to describe the comprehensive strategy that the body utilizes to adapt to dynamic environmental conditions. We discuss the hypothesis that a bow‐tie architecture might be suitable to describe the variety of immune–neuroendocrine inputs that continuously target cells and organs while, at the same time, fulfilling the basic requirement of minimizing the cost of immune–neuroendocrine responses. Bow‐tie architectures are able to convert a variety of stimuli (fan in) into a wide range of fine‐tuned responses (fan out) by passing through the integrating activity of a core (knot) constituted by a limited number of elements. Finally, we argue that the ecologically negotiated immune–neuroendocrine strategies may have deleterious effects in the post‐reproductive period of life when, at least in humans, chronic, low‐grade, systemic inflammation develops, in accordance with the antagonistic pleiotropy theory of aging. BioEssays 30:868–874, 2008. © 2008 Wiley Periodicals, Inc. (shrink)