Aging induces region-specific dysregulation of hormone synthesis in the primate adrenal gland PMID: 38503993

ADC Targets in Oncology

2026-04-10

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

Nat Aging. 2024 Mar;4(3):396-413. doi: 10.1038/s43587-024-00588-1.

Qiaoran Wang ^# ¹ ² , Xuebao Wang ^# ² ³ ⁴ ⁵ ⁶ , Beibei Liu ^# ¹ , Shuai Ma ^# ⁴ ⁵ ⁶ ⁷ , Feng Zhang ^# ⁸ ⁹ , Shuhui Sun ⁴ ⁵ ⁶ ⁷ , Yaobin Jing ⁴ ¹⁰ , Yanling Fan ¹ , Yingjie Ding ¹ ² , Muzhao Xiong ¹ ² , Jiaming Li ¹ ² , Qiaocheng Zhai ⁸ ⁹ , Yandong Zheng ² ³ ⁴ ⁵ ⁶ , Chengyu Liu ² ³ ⁴ ⁵ ⁶ , Gang Xu ¹¹ ¹² , Jiayin Yang ¹¹ ¹² , Si Wang ¹³ ¹⁴ ¹⁵ ¹⁶ , Jinlin Ye ⁹ , Juan Carlos Izpisua Belmonte ¹⁷ , Jing Qu ¹⁸ ¹⁹ ²⁰ ²¹ ²² ²³ , Guang-Hui Liu ²⁴ ²⁵ ²⁶ ²⁷ ²⁸ ²⁹ ³⁰ ³¹ ³² , Weiqi Zhang ³³ ³⁴ ³⁵ ³⁶

Affiliations

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.
18. University of Chinese Academy of Sciences, Beijing, China. [email protected].
19. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [email protected].
20. Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [email protected].
21. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. [email protected].
22. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. [email protected].
23. Aging Biomarker Consortium, Beijing, China. [email protected].
24. University of Chinese Academy of Sciences, Beijing, China. [email protected].
25. Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [email protected].
26. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. [email protected].
27. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. [email protected].
28. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [email protected].
29. International Center for Aging and Cancer, Hainan Medical University, Haikou, China. [email protected].
30. Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital, Capital Medical University, Beijing, China. [email protected].
31. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, China. [email protected].
32. Aging Biomarker Consortium, Beijing, China. [email protected].
33. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China. [email protected].
34. University of Chinese Academy of Sciences, Beijing, China. [email protected].
35. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. [email protected].
36. Aging Biomarker Consortium, Beijing, China. [email protected].
# Contributed equally.

Abstract

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.