Time-restricted eating reveals a “younger” immune system and reshapes the intestinal microbiome in human
Yiran Chen,
Xi Li,
Ming Yang,
Chen Jia,
Zhenghao He,
Suqing Zhou,
Pinglang Ruan,
Yikun Wang,
Congli Tang,
Wenjing Pan,
Hai Long,
Ming Zhao,
Liwei Lu,
Weijun Peng,
Arne Akbar,
Irene XY. Wu,
Song Li,
Haijing Wu,
Qianjin Lu
Affiliations
Yiran Chen
Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, China
Xi Li
Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China
Ming Yang
Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China
Chen Jia
Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China
Zhenghao He
Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China
Suqing Zhou
Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China
Pinglang Ruan
Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China
Yikun Wang
Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
Congli Tang
Nanjing ARP Biotechnology Co., Ltd, Nanjing, 210046, China
Wenjing Pan
Nanjing ARP Biotechnology Co., Ltd, Nanjing, 210046, China; Hunan Key Laboratory of Biomedical Nanomaterials and Devices, Hunan University of Technology, Zhuzhou, 412007, China
Hai Long
Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China
Ming Zhao
Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, China; Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China
Liwei Lu
Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, 518057, China
Weijun Peng
Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
Arne Akbar
Associate of the Institute of Healthy Ageing, Division of Infection & Immunity, University College of London, London, WC1E 6BT, United Kingdom
Irene XY. Wu
Xiangya School of Public Health, Central South University, 4/F, Changsha, Hunan, 410006, China
Song Li
Corresponding author. Key Laboratory of Rare Pediatric Diseases, Ministry of Education, Hengyang Medical School, University of South China, Hengyang, Hunan, China.; Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, 210042, China; Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, 210042, China; Research Unit of Key Technologies of Immune-related Skin Diseases Diagnosis and Treatment, Chinese Academy of Medical Sciences Institute of Dermatology, Nanjing, 210042, China; Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China; Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, China; Nanjing ARP Biotechnology Co., Ltd, Nanjing, 210046, China; Hunan Key Laboratory of Biomedical Nanomaterials and Devices, Hunan University of Technology, Zhuzhou, 412007, China; Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, 518057, China; Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China; Associate of the Institute of Healthy Ageing, Division of Infection & Immunity, University College of London, London, WC1E 6BT, United Kingdom; Xiangya School of Public Health, Central South University, 4/F, Changsha, Hunan, 410006, China; Key Laboratory of Rare Pediatric Diseases, Ministry of Education, Hengyang Medical School, University of South China, Hengyang, Hunan, China; National Health Commission Key Laboratory of Birth Defect Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China
Haijing Wu
Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China; Corresponding author.
Qianjin Lu
Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, China; Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China; Corresponding author. Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, China.
Time-restricted eating (TRE) has been shown to extent lifespans in drosophila and mouse models by affecting metabolic and anti-inflammatory activities. However, the effect of TRE on the human immune system, especially on immunosenescence, intestinal microbiome, and metabolism remains unclear. We conducted a 30-day 16:8 TRE single-arm clinical trial with 49 participants. Participants consumed daily meals from 9 a.m. to 5 p.m., provided by a nutrition canteen with a balanced, calorie-appropriate nutrition, which is designed by clinical nutritionists (ChiCTR2200058137). We monitored weight changes and weight-related parameters and focused on changes in the frequency of CD4+ senescent T cells, immune repertoire from peripheral blood, as well as serum metabolites and gut microbiota. We found that up to 95.9 % of subjects experienced sustained weight loss after TRE. The frequency of circulating senescent CD4+ T cells was decreased, while the frequency of Th1, Treg, Tfh-like, and B cells was increased. Regarding the immune repertoire, the proportions of T cell receptor alpha and beta chains were increased, whereas B cell receptor kappa and lambda chains were reduced. In addition, a reduced class switch recombination from immunoglobulin M (IgM) to immunoglobulin A (IgA) was observed. TRE upregulated the levels of anti-inflammatory and anti-aging serum metabolites named sphingosine-1-phosphate and prostaglandin-1. Additionally, several anti-inflammatory bacteria and probiotics were increased, such as Akkermansia and Rikenellaceae, and the composition of the gut microbiota tended to be “younger”. Overall, TRE showed multiple anti-aging effects, which may help humans maintain a healthy lifestyle to stay “young”. Clinical Trial Registration URL: https://www.chictr.org.cn/showproj.html?proj=159876.
