title: Drivers of age-related inflammation and strategies for healthspan extension.
abstract: Aging is the greatest risk factor for the development of chronic diseases such as arthritis, type 2 diabetes, cardiovascular disease, kidney disease, Alzheimer's disease, macular degeneration, frailty, and certain forms of cancers. It is widely regarded that chronic inflammation may be a common link in all these age-related diseases. This raises the question, can one alter the course of aging and potentially slow the development of all chronic diseases by manipulating the mechanisms that cause age-related inflammation? Emerging evidence suggests that pro-inflammatory cytokines interleukin-1 (IL-1) and IL-18 show an age-dependent regulation implicating inflammasome-mediated caspase-1 activation in the aging process. The Nod-like receptor (NLR) family of innate immune cell sensors, such as the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome controls the caspase-1 activation in myeloid-lineage cells in several organs during aging. The NLRP3 inflammasome is especially relevant to aging as it can get activated in response to structurally diverse damage-associated molecular patterns (DAMPs) such as extracellular ATP, excess glucose, ceramides, amyloids, urate, and cholesterol crystals, all of which increase with age. Interestingly, reduction in NLRP3-mediated inflammation prevents age-related insulin resistance, bone loss, cognitive decline, and frailty. NLRP3 is a major driver of age-related inflammation and therefore dietary or pharmacological approaches to lower aberrant inflammasome activation holds promise in reducing multiple chronic diseases of age and may enhance healthspan.
authors: Section of Comparative Medicine, Yale School of Medicine, New Haven, CT, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
authors: Emily L
authors: EL
authors: Goldberg
authors: Vishwa Deep
authors: VD
authors: Dixit
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
chemical_list: D002352:Carrier Proteins; D007375:Interleukin-1; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D020170:Caspase 1
keywords: IL-1; IL-18; NLRP3; adipose tissue; cytokines; inflammasome; macrophage; sarcopenia; senescence