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
Affiliations
Ming Wang
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan 450052, China
Yan Yan
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan 450052, China
Zhengguo Zhang
Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Xiaohan Yao
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan 450052, China
Xixi Duan
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan 450052, China
Ziming Jiang
Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Junfeng An
School of Yunkang Medical and Health Management, Nanfang College of SUN Yat-Sen University, Guangzhou city, Guangdong 510970, China
Peiguo Zheng
Clinical Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
Yijie Han
University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Hao Wu
Würzburg Institute of Systems Immunology, Max-planck Research Group, University Würzburg, Germany
Zhaoqing Wang
Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Rainer Glauben
Corporate Member of Freie Universität Berlin, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Medical Department for Gastroenterology, Infectious Diseases and Rheumatology, Berlin Institute of Health, Berlin, Germany
Zhihai Qin
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan 450052, China; Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; School of Basic Medical Sciences, the Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan 450052, China; Corresponding author
Summary: 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.
