# Exploring the Plasma Proteome: Identifying Hub Proteins linking Aging, Homeostasis, and Organ Function

**Authors:** Juan Jiao, Fei Gao, Hongye Zhao, Mingjun Jiang, Yan Zhou, Dizhi Liu, Sihang Fang, Danni Gao, Zhaoping Wang, Ze Yang, Huiping Yuan

PMC · DOI: 10.7150/ijms.107750 · 2025-02-10

## TL;DR

This study identifies 20 plasma proteins linked to aging and health, showing how they relate to metabolism, inflammation, and organ function.

## Contribution

The first study to connect aging and homeostasis through plasma proteins, identifying 20 hub proteins and 8 key ones affecting organ function.

## Key findings

- 20 hub proteins correlate with age and physiological indices, involved in oxidative stress, inflammation, and metabolism.
- Eight hub proteins (CD44, CD14, IGF2, CFD, LBP, IGFBP3, EFEMP1, AHSG) affect organ function by mediating homeostasis.
- Plasma proteins reflect aging and health, with expression patterns changing across the lifespan.

## Abstract

As effectors of interactions between genes and the environment, plasma proteins can monitor homeostasis and reflect the aging state of an organism. However, biomarkers of aging that are associated with homeostasis are still unclear. This study investigates the phenotype-related plasma proteome profiles of healthy individuals and to identify proteins that are specifically related to aging and physiological indices and their expression patterns across the lifespan. From September 2020 to March 2021, 71 participants aged over 20 to 100 years were enrolled in this cross-sectional study. Data were analyzed from April 2021 to December 2023. The plasma proteome was analyzed to identify proteins that are specifically related to aging and their expression patterns across the lifespan. Then, hub proteins were screened through correlation of aging proteins with physiological and biochemical phenotypes. Based on levels of plasma proteins, physiological indices are associated with age. Additionally, these differences in protein expression correlate with age and physiological indices. Finally, we identified 20 hub proteins that correlate with both physiological indices and age, and these proteins are involved in oxidative stress, inflammation and metabolism. Bibliometric analysis confirmed that 8 hub proteins (CD44, CD14, IGF2, CFD, LBP, IGFBP3, EFEMP1, and AHSG) associated with age affect organ function by mediating homeostasis. Plasma proteins associated with both age and physiological indices are involved in oxidative stress, inflammation, and metabolism. This is the first investigation to link aging and homeostasis based on plasma proteins.

## Linked entities

- **Proteins:** CD44 (CD44 molecule (IN blood group)), CD14 (CD14 molecule), IGF2 (insulin like growth factor 2), CFD (complement factor D), LBP (lipopolysaccharide binding protein), IGFBP3 (insulin like growth factor binding protein 3), EFEMP1 (EGF-like fibulin extracellular matrix protein 1), AHSG (alpha 2-HS glycoprotein)

## Full-text entities

- **Genes:** CFD (complement factor D) [NCBI Gene 1675] {aka ADIPSIN, ADN, DF, PFD}, EFEMP1 (EGF-like fibulin extracellular matrix protein 1) [NCBI Gene 2202] {aka ARCL1D, DHRD, DRAD, FBLN3, FBNL, FIBL-3}, CD14 (CD14 molecule) [NCBI Gene 929], IGFBP3 (insulin like growth factor binding protein 3) [NCBI Gene 3486] {aka BP-53, IBP-3, IBP3, IGFBP-3}, IGF2 (insulin like growth factor 2) [NCBI Gene 3481] {aka C11orf43, GRDF, IGF-II, PP9974, SRS3}, LBP (lipopolysaccharide binding protein) [NCBI Gene 3929] {aka BPIFD2}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, AHSG (alpha 2-HS glycoprotein) [NCBI Gene 197] {aka A2HS, AHS, APMR1, FETUA, HSGA}
- **Diseases:** inflammation (MESH:D007249)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11866526/full.md

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Source: https://tomesphere.com/paper/PMC11866526