Drivers of age‐related inflammation and strategies for healthspan extension

EL Goldberg, VD Dixit - Immunological reviews, 2015 - Wiley Online Library
Immunological reviews, 2015Wiley Online Library
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 …
Summary
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.
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