Inflamm-Aging

Inflammaging is a theory of aging based on the evidence that the evolutionary unpredicted persistent/increasing exposure to a variety of external and internal stressors occurring beyond the age of reproduction activates innate and adaptive immunity pathways involved in inflammatory response. Seventeen years after this theory was launched, it is now recognized that this phenomenon also involves non-immune cells, including adipocytes, fibroblasts, muscle, endothelial, and senescent cells. Recent data suggest that besides classical stimuli, such as cyto- megalovirus persistent infection (non-self), inflammging is fueled by a variety of stimuli derived from the gut microbiota (quasi-self) and by the continuous production of potentially inflammatory molecules released/secreted as a conse- quence of cell death and organelle dysfunction (self). All these products (alarmins) are sensed by a small number of evolutionary-selected sensors, and eventually activate few basic inflammatory pathways such as NF-κB, inflammasomes, and cGAS. These phenomena are physiological and crucial for survival, but they undergo a progressive increase with age, sometimes reaching a threshold over which age-related pathologies ensue, thus representing an example of antagonist pleiotropy. Inflammaging is a dynamic phenomenon, and its final clinical outcome is highly “personalized” depending on what we propose to call “immunobiography,” i.e., the lifelong immunological experiences and stimuli each individual has been exposed to. Finally, a particular attention is devoted to antiaging strategies, showing that most of them have a direct or indirect impact on inflammaging itself.