Brain HealthThree Aging Mechanisms Fuel Neurodegeneration Together — A Unified Framework
Researchers at Jawaharlal Nehru University propose a unified 'Autophagy-Senescence-Inflammasome (ASI) axis' to explain why chronic brain inflammation persists in neurodegenerative diseases. Rather than treating autophagy dysfunction, glial cell senescence, and inflammasome signaling as separate problems, this review argues they form a self-sustaining loop. When cells fail to clear debris via autophagy, mitochondria become dysfunctional, generating danger signals. Senescent astrocytes and microglia then release inflammatory proteins through a process called SASP, which further activates the inflammasome — an immune alarm system. Each process amplifies the others. This framework applies across Alzheimer's, Parkinson's, ALS, multiple sclerosis, stroke, and chronic pain. The authors argue that targeting all three arms simultaneously may outperform current single-target drug strategies.
