The immunology behind inflammaging-causes, sources, and mechanisms

Inflammaging, the aberrant chronic inflammatory state at advanced age, is an immunological phenomenon associated with detrimental long-term health consequences, morbidity, and mortality. Although the precise etiology of inflammaging is elusive, emerging evidence indicates that molecular and cellular changes in immune cells drive inflammaging directly through heightened cytokine production and indirectly via inflammatory cell death and ineffective neutralization of inflammatory cellular waste. Additionally, nonimmune tissue cells, particularly senescent cells, amplify the heightened inflammatory environment with age via their secretome and by modulating the immune system. The systemic concentrations of inflammatory mediators during aging is in the same range as those seen in mild, acute viral infections. Intriguingly, centenarians, who exhibit exceptional health span and longevity do not evade inflammaging but appear to neutralize its downstream effects through negative molecular or cellular feedback mechanisms. Collectively, this review positions inflammaging as a dynamic and multifactorial process arising from coordinated immune and nonimmune dysfunction while outlining opportunities to counter age-related inflammation.