Association of Autophagy and Inflammation with Aging

Abstract

Autophagy is a catabolic process by which cells degrade damaged organelles via lysosomal degradation and recycle intracellular macromolecules and organelles to produce ATP. Autophagy clears cytosolic molecules that have a potential role in inflammasome formation. Hyperinflammation in the aging process can cause inflammasome formation that results in multiple inflammatory response-mediated diseases. Damaged mitochondria may induce oxidative stress in cells via ROS which leads to the activation of the inflammasome. Therefore, mitophagy-induced suppression of inflammasome can reduce oxidative stress. Inflammation in aging comes with diseases such as Alzheimer’s disease and Parkinson’s disease. Decreased function of autophagy in aging is the main reason behind the improper clearing of cytosolic organelles and induction of inflammation. Autophagy can slow down aging in cells and many other disorders by suppressing inflammatory genes. Also, ROS can directly activate NLRP3 and other proinflammatory pathways that increase in aging. Suppression of the NLRP3 gene which is responsible for inflammasome formation showed inhibition of the PI3K/mTOR/AKT pathway, which is directly linked to autophagy. This suppression of NLRP3 promoted longevity in cells. The interrelation between such pathway data mining from various biological databases can resolve the complex interconnection between autophagy and inflammatory pathways which can elucidate its role in aging. By using various bioinformatics tools such as DAVID and CYTOSPACE, string matching will confirm and support a relationship between the pathways. This will give a better level of understanding of interrelated pathways of autophagy, inflammation and aging.