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The Effect of Aging on Tissues

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Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...

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Updated: Sep 9, 2025

Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome

Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome

Published on: February 24, 2023

A single-cell transcriptomic landscape characterizes the endocrine system aging in the mouse.

Ran Wei¹, Zhehao Du¹, Jue Wang^2,3,4

¹The State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China.

|September 3, 2025

Summary

Aging impairs endocrine organs by activating specific cellular pathways and increasing immune cell infiltration. Targeting immune responses may counteract aging effects in the endocrine system.

Keywords:

GZMK MHC-I aging endocrine system immune infiltration single-cell RNA-seq

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Last Updated: Sep 9, 2025

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Single-cell Transcriptomic Analyses of Mouse Pancreatic Endocrine Cells

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Area of Science:

Endocrinology
Immunology
Gerontology

Background:

The endocrine system is vital for homeostasis, but its aging process at the cellular level is poorly understood.
Aging affects various organs, yet comprehensive single-cell analyses of endocrine organ aging are lacking.

Purpose of the Study:

To elucidate the cellular and molecular mechanisms driving endocrine system aging.
To identify cell-type-specific aging signatures across multiple endocrine organs.
To investigate the role of immune infiltration in endocrine aging.

Main Methods:

Single-cell RNA sequencing of eight endocrine organs from young and aged mice.
Analysis of cell-type-specific gene expression, aging pathways, and immune responses.
Machine learning to identify novel aging biomarkers.

Main Results:

Aging activates specific pathways like loss of proteostasis, genomic instability, and reactive oxygen species (ROS).
Functional endocrine cells show impaired gene networks, increased immune infiltration, and unfolded protein response (UPR).
Exhausted T cells release GZMK, activating the MHC-I-UPR axis; CD59 identified as an aging feature.
Sex-specific organs exhibit enhanced immune responses, with ovaries showing increased ROS and testes impaired DNA repair.

Conclusions:

Immune infiltration, driven by exhausted T cells, is a potential driver of endocrine aging.
Cell-type-specific aging mechanisms vary across endocrine organs.
This study provides a high-resolution map of endocrine aging, revealing new therapeutic targets.