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Aging induces region-specific dysregulation of hormone synthesis in the primate adrenal gland

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收录情况： ◇ SCIE

作者：
Wang Qiaoran[1,2] ; Wang Xuebao[2,3,4,5,6] ; Liu Beibei[1] ; Ma Shuai[4,5,6,7] ; Zhang Feng[8,9] ; Sun Shuhui[4,5,6,7] ; Jing Yaobin[4,10] ; Fan Yanling[1] ; Ding Yingjie[1,2] ; Xiong Muzhao[1,2] ; Li Jiaming[1,2] ; Zhai Qiaocheng[8,9] ; Zheng Yandong[2,3,4,5,6] ; Liu Chengyu[2,3,4,5,6] ; Xu Gang[11,12] ; Yang Jiayin[11,12] ; Wang Si[13,14,15,16] ; Ye Jinlin[9] ; Izpisua Belmonte Juan Carlos[17] ; Qu Jing[2,3,4,5,6,16] ; Liu Guang-Hui[2,4,5,6,7,10,13,14,16] ; Zhang Weiqi[1,2,5,16] ;
机构： [1]CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China. [2]University of Chinese Academy of Sciences, Beijing, China. [3]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [4]Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [5]Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. [6]Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. [7]State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [8]Division of Endocrinology, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China. [9]The Joint Innovation Center for Engineering in Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China. [10]International Center for Aging and Cancer, Hainan Medical University, Haikou, China. [11]Liver Transplant Center, Organ Transplant Center, West China Hospital of Sichuan University, Chengdu, China. [12]Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital of Sichuan University, Chengdu, China. [13]Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital, Capital Medical University, Beijing, China. [14]Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, China. [15]The Fifth People’s Hospital of Chongqing, Chongqing, China. [16]Aging Biomarker Consortium, Beijing, China. [17]Altos Labs, San Diego, CA, USA
出处：
DOI： 10.1038/s43587-024-00588-1

摘要：
Adrenal glands, vital for steroid secretion and the regulation of metabolism, stress responses and immune activation, experience age-related decline, impacting systemic health. However, the regulatory mechanisms underlying adrenal aging remain largely uninvestigated. Here we established a single-nucleus transcriptomic atlas of both young and aged primate suprarenal glands, identifying lipid metabolism and steroidogenic pathways as core processes impacted by aging. We found dysregulation in centripetal adrenocortical differentiation in aged adrenal tissues and cells in the zona reticularis region, responsible for producing dehydroepiandrosterone sulfate (DHEA-S), were highly susceptible to aging, reflected by senescence, exhaustion and disturbed hormone production. Remarkably, LDLR was downregulated in all cell types of the outer cortex, and its targeted inactivation in human adrenal cells compromised cholesterol uptake and secretion of dehydroepiandrosterone sulfate, as observed in aged primate adrenal glands. Our study provides crucial insights into endocrine physiology, holding therapeutic promise for addressing aging-related adrenal insufficiency and delaying systemic aging.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.

基金：
This work was supported by the National Key Research and Development Program of China (2022YFA1103700), the National Natural Science Foundation of China (82125011, 81921006, 92149301, 82122024, 92168201, 92049116 and 82361148131), the National Key Research and Development Program of China (2020YFA0804000, 2020YFA0112200, 2021YFF1201000, 2022YFA1103800, the STI2030-Major Projects-2021ZD0202400 and 2021YFA1101000), the National Key Research and Development Program of China (82330044, 32341001, 92049304, 32121001, 82192863, 82361148130, 82301758, 82271600, 82322025 and 82071588), CAS Project for Young Scientists in Basic Research (YSBR-076 and YSBR-012), the Program of the Beijing Natural Science Foundation (Z230011), the Informatization Plan of Chinese Academy of Sciences (CAS-WX2022SDC-XK14), New Cornerstone Science Foundation through the XPLORER PRIZE (2021-1045), Youth Innovation Promotion Association of CAS (E1CAZW0401, 2022083 and 2023092), Young Elite Scientists Sponsorship Program by CAST (2021QNRC001), Excellent Young Talents Program of Capital Medical University (12300927), the Project for Technology Development of Beijing-affiliated Medical Research Institutes (11000023T000002036310), and Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team (BPHR202203105), the Quzhou Technology Projects (2022K46).
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外文
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出版当年[2023]版：
Q1 CELL BIOLOGY Q1 GERIATRICS & GERONTOLOGY Q1 NEUROSCIENCES
最新[2023]版：
Q1 CELL BIOLOGY Q1 GERIATRICS & GERONTOLOGY Q1 NEUROSCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2023版]

第一作者：
第一作者机构： [1]CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China. [2]University of Chinese Academy of Sciences, Beijing, China.
共同第一作者：
通讯作者：
通讯机构： [1]CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China. [2]University of Chinese Academy of Sciences, Beijing, China. [3]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [4]Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [5]Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. [6]Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. [7]State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [10]International Center for Aging and Cancer, Hainan Medical University, Haikou, China. [13]Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital, Capital Medical University, Beijing, China. [14]Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, China. [16]Aging Biomarker Consortium, Beijing, China.
推荐引用方式(GB/T 7714)：
Wang Qiaoran,Wang Xuebao,Liu Beibei,et al.Aging induces region-specific dysregulation of hormone synthesis in the primate adrenal gland[J].Nature Aging.2024,4(3):396-413.doi:10.1038/s43587-024-00588-1.
APA：
Wang Qiaoran,Wang Xuebao,Liu Beibei,Ma Shuai,Zhang Feng...&Zhang Weiqi.(2024).Aging induces region-specific dysregulation of hormone synthesis in the primate adrenal gland.Nature Aging,4,(3)
MLA：
Wang Qiaoran,et al."Aging induces region-specific dysregulation of hormone synthesis in the primate adrenal gland".Nature Aging 4..3(2024):396-413

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