Nutrition Videos

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Immunometabolic Regulators of Age-Related Inflammation

Speakers: V. D. Dixit

Presented at Nestlé International Nutrition Symposium (NINs)

Summary

Emerging data that innate immune sensor NLRP3 inflammasome links aging to functional decline support Metchnikoff’s original prediction that phagocytes or macrophages drive aging-associated degenerative diseases in an organism. Here we detail a mechanism by which the macrophage-expressed NLRP3 inflammasome controls age-related inflammation in periphery as well as brain. Ablation of NLRP3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome, and astrogliosis.Furthermore, downregulation of NLRP3 in aged mice protected against age-related loss of memory and cognition. The ketone metabolite β hydroxybutyrate (BHB) that is elevated by caloric restriction, high-intensity exercise, or the low-carbohydrate ketogenic diet serves as an endogenous negative regulator of NLRP3-driven inflammation. These studies suggest that NLRP3 inflammasome is a major driver of age-related inflammation and therefore dietary or pharmacological approaches to lower NLRP3 holds promise in reducing multiple chronic diseases of age.