Inflammaging and 'Garb-aging'

'Inflammaging' refers to the chronic, low-grade inflammation that characterizes aging. Inflammaging is macrophage centered, involves several tissues and organs, including the gut microbiota, and is characterized by a complex balance between pro- and anti-inflammatory responses. Based on literature data, we argue that the major source of inflammatory stimuli is represented by endogenous/self, misplaced, or altered molecules resulting from damaged and/or dead cells and organelles (cell debris), recognized by receptors of the innate immune system. While their production is physiological and increases with age, their disposal by the proteasome via autophagy and/or mitophagy progressively declines. This 'autoreactive/autoimmune' process fuels the onset or progression of chronic diseases that can accelerate and propagate the aging process locally and systemically. Consequently, inflammaging can be considered a major target for antiaging strategies. Human aging is characterized by a state of chronic, low-grade, sterile inflammation (inflammaging), the causes of which are poorly understood.A possible cause of inflammaging is the continuous stimulation of macrophages by molecular garbage whose generation-disposal balance becomes impaired with age.Misplaced self-molecules can be sensed by macrophage receptors and contribute to inflammaging by activating the inflammasome.Self-molecules (nuclear and/or mtDNA), and other cellular garbage and signaling molecules (miRNAs) freely circulate in bodily fluids within extracellular vesicles carrying inflammatory signals that can spread to distal cells and tissues.Age-related mitochondrial dysfunction could be linked to inflammaging (source of oxidative stress) and 'self garbage' (mtDNA, cardiolipin, or formyl peptides) that can be sensed by macrophages.