title: Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases.
abstract: Oxidative stress and low-grade inflammation are the hallmarks of the aging process and are even more enhanced in many age-related degenerative diseases. Mitochondrial dysfunction and oxidative stress can provoke and potentiate inflammatory responses, but the mechanism has remained elusive. Recent studies indicate that oxidative stress can induce the assembly of multiprotein inflammatory complexes called the inflammasomes. Nod-like receptor protein 3 (NLRP3) is the major immune sensor for cellular stress signals, e.g., reactive oxygen species, ceramides, and cathepsin B. NLRP3 activation triggers the caspase-1-mediated maturation of the precursors of IL-1β and IL-18 cytokines. During aging, the autophagic clearance of mitochondria declines and dysfunctional mitochondria provoke chronic oxidative stress, which disturbs the cellular redox balance. Moreover, increased NF-κB signaling observed during aging could potentiate the expression of NLRP3 and cytokine proforms enhancing the priming of NLRP3 inflammasomes. Recent studies have demonstrated that NLRP3 activation is associated with several age-related diseases, e.g., the metabolic syndrome. We will review here the emerging field of inflammasomes in the appearance of the proinflammatory phenotype during the aging process and in age-related diseases.
authors.affiliation: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland. antero.salminen@uef.fi
authors.forename: Antero
authors.initials: A
authors.lastname: Salminen
authors.forename: Johanna
authors.initials: J
authors.lastname: Ojala
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
authors.forename: Anu
authors.initials: A
authors.lastname: Kauppinen
mesh_terms: D000375:Aging / Q000502:physiology*; D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology; D001343:Autophagy; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D004272:DNA, Mitochondrial; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D002518:Ceramides; D004272:DNA, Mitochondrial; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D020170:Caspase 1