Longevity & AgingHow Aging Breaks the Immune System — and How We Might Fix It
Immunosenescence — the progressive decline and dysregulation of immune function with age — is driven by interconnected signaling pathway failures, accumulation of senescent cells, and shifts in immune cell populations. Key pathways including NF-κB, mTOR, JAK-STAT, and cGAS-STING become overactivated with age, while protective pathways like AMPK, melatonin, and sirtuins are suppressed. Together, these changes fuel chronic low-grade inflammation (inflammaging), reduce vaccine efficacy, impair pathogen clearance, and raise risks of cancer, neurodegenerative disease, cardiovascular disease, and autoimmunity. The review synthesizes current intervention strategies — from rapamycin analogs and senolytics to lifestyle and nutritional approaches — and highlights clinical trials already underway.
