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  3. Age-, sex- and proximal-distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates

Age-, sex- and proximal-distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates

  • Nat Aging. 2024 Feb 6. doi: 10.1038/s43587-024-00572-9.
Xinyuan Wang # 1 2,  Yaru Luo # 1,  Siyu He # 1,  Ying Lu # 1,  Yanqiu Gong # 1,  Li Gao 1,  Shengqiang Mao 1,  Xiaohui Liu 3,  Na Jiang 2,  Qianlun Pu 2,  Dan Du 2,  Yang Shu 1,  Shan Hai 1,  Shuangqing Li 1,  Hai-Ning Chen 4,  Yi Zhao 5,  Dan Xie 1,  Shiqian Qi 1,  Peng Lei 1,  Hongbo Hu 1,  Heng Xu 1,  Zong-Guang Zhou 4,  Biao Dong 6,  Huiyuan Zhang 7,  Yan Zhang 8,  Lunzhi Dai 9
Affiliations

Affiliations

  • 1 National Clinical Research Center for Geriatrics, Center for Immunology and Hematology and General Practice Ward/International Medical Center Ward, General Practice Medical Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
  • 2 Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
  • 3 School of Life Sciences, Tsinghua University, Beijing, China.
  • 4 Colorectal Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
  • 5 Department of Rheumatology and Immunology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
  • 6 National Clinical Research Center for Geriatrics, Center for Immunology and Hematology and General Practice Ward/International Medical Center Ward, General Practice Medical Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. biaodong@scu.edu.cn.
  • 7 National Clinical Research Center for Geriatrics, Center for Immunology and Hematology and General Practice Ward/International Medical Center Ward, General Practice Medical Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. hyzhang@scu.edu.cn.
  • 8 National Clinical Research Center for Geriatrics, Center for Immunology and Hematology and General Practice Ward/International Medical Center Ward, General Practice Medical Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. yanzhang@scu.edu.cn.
  • 9 National Clinical Research Center for Geriatrics, Center for Immunology and Hematology and General Practice Ward/International Medical Center Ward, General Practice Medical Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. lunzhi.dai@scu.edu.cn.
  • # Contributed equally.
PMID: 38321225 DOI: 10.1038/s43587-024-00572-9
Abstract

The incidence of intestinal diseases increases with age, yet the mechanisms governing gut aging and its link to diseases, such as colorectal Cancer (CRC), remain elusive. In this study, while considering age, sex and proximal-distal variations, we used a multi-omics approach in non-human primates (Macaca fascicularis) to shed LIGHT on the heterogeneity of intestinal aging and identify potential regulators of gut aging. We explored the roles of several regulators, including those from tryptophan metabolism, in intestinal function and lifespan in Caenorhabditis elegans. Suggesting conservation of region specificity, tryptophan metabolism via the kynurenine and serotonin (5-HT) pathways varied between the proximal and distal colon, and, using a mouse colitis model, we observed that distal colitis was more sensitive to 5-HT treatment. Additionally, using proteomics analysis of human CRC samples, we identified links between gut aging and CRC, with high HPX levels predicting poor prognosis in older patients with CRC. Together, this work provides potential targets for preventing gut aging and associated diseases.

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