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标题：Programmed PPAR-α downregulation induces inflammaging by suppressing fatty acid catabolism in monocytes
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作者：Ming Wang ; Yan Yan ; Zhengguo Zhang 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：7
页码：1-22
DOI：10.1016/j.isci.2021.102766
语种：English
出版社：Elsevier
摘要：SummaryInflammaging is associated with an increased risk of chronic disease. Monocytes are the principal immune cells for the production of inflammatory cytokines and contribute to inflammaging in the elderly. However, the underlying mechanisms remain largely unknown. Here, we found that monocytes from aged individuals contained high levels of lipid droplets (LDs), and this increase was correlated with impaired fatty acid oxidation. Downregulated peroxisome proliferator-activated receptor (PPAR)-α may be responsible for the pro-inflammatory phenotype of monocytes in aged individuals, as it was positively correlated with LD accumulation and increasing TNF-α concentration. Interestingly, interventions that result in PPAR-α upregulation, such as fenofibrate treatment, TNF-α neutralization, or calorie restriction, reversed the effect of aging on monocytes. Thus the downregulation of PPAR-α and LD levels in monocytes represents a novel biomarker for inflammaging. Furthermore, PPAR-α activation in the elderly may also alleviate long-term inflammaging, preventing the development of life-limiting chronic diseases.Graphical abstractDisplay OmittedHighlights•Monocytes from aged individuals contained high levels of lipid droplets (LDs)•Downregulated PPAR-α is responsible for the aged monocytes profiles•TNF-α might accelerate monocyte aging by downregulating PPAR-α expression•PPAR-α activation in the elderly may also alleviate long-term inflammagingHuman metabolism; Immunology; Cell biology