Programmed PPAR-α downregulation induces inflammaging by suppressing fatty acid catabolism in monocytes
Ming Wang, Yan Yan, Zhengguo Zhang, Xiaohan Yao, Xixi Duan, Ziming Jiang, Junfeng An, Peiguo Zheng, Yijie Han, Hao Wu, Zhaoqing Wang, Rainer Glauben, Zhihai Qin
Abstract
Inflammaging 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.