Abstract
A natural consequence of everyday tissue metabolism is cell injury or stress. This injury activates a canonical immune-mediated inflammatory response in order to achieve tissue repair so that homeostasis is maintained. With aging there is increased tissue injury and therefore increasing demands placed on an immune system, which itself is aging (immunosenescence). Thus, the increased reparative demands are reflected by an increased inflammatory load both locally and systemically. Eventually, if the reparative demands are excessive, the aging immune system is overwhelmed and disease ensues. In the macula this age-related failure in repair gives rise to age-related macular degeneration (AMD). The hypothesis proposed herein is therefore, that AMD is due to age-related failure of tissue repair and the chronic inflammation associated with this failure ('inflammaging') is both a surrogate and biomarker of this reparative failure and not in itself the primary cause of disease. Such a hypothesis can be applied to all the diseases of aging and by extension suggests that effective therapies should be aimed at facilitating repair through immunotherapy, possibly and perhaps controversially, through the promotion of inflammation rather than the current approach of its inhibition (anti-inflammatory strategies), the latter which can ultimately only hinder the repair process and thereby lead to the persistence of disease.
NSTL
Elsevier