# Effects of Chlorogenic Acid on Cellular Senescence in an In Vitro Model of 3T3-L1 Murine Adipocytes

**Authors:** Maria Sofia Molonia, Federica Lina Salamone, Santi Trischitta, Antonella Saija, Francesco Cimino, Antonio Speciale

PMC · DOI: 10.3390/molecules31010167 · Molecules · 2026-01-01

## TL;DR

This study shows that chlorogenic acid can reduce cellular aging in fat cells, potentially offering a new dietary supplement to combat age-related metabolic issues.

## Contribution

The novel contribution is demonstrating chlorogenic acid's ability to alleviate adipocyte senescence through multiple molecular pathways.

## Key findings

- Chlorogenic acid restored Lamin B1 levels and the Bcl-2/Bax ratio in senescent adipocytes.
- It modulated p53, p21, and MAPK signaling while improving insulin signaling via the PI3K-AKT-GLUT4 axis.
- CGA reduced oxidative stress, inflammation, and SASP factors linked to cellular senescence.

## Abstract

Cellular senescence is a stress-induced process that contributes to adipose tissue dysfunction by promoting inflammation, impaired adipogenesis, and insulin resistance, alterations that are closely associated with age-related cellular dysfunction and metabolic disorders. In this study, we evaluated the protective role of chlorogenic acid (CGA), a polyphenol with known antioxidant and anti-inflammatory properties, against oxidative stress-induced senescence in murine 3T3-L1 adipocytes. The results obtained showed that CGA treatment significantly alleviated the senescent phenotype by restoring Lamin B1 levels and the Bcl-2/Bax ratio. Additionally, CGA downregulated key senescence-related cell cycle progression markers, modulating p53, p21, and MAPK signaling. CGA also restored insulin signaling through the PI3K-AKT-GLUT4 axis and improved glucose uptake, while attenuating oxidative stress, inflammatory cytokine expression, and extracellular matrix remodeling factors associated with SASP. Collectively, these findings support the role of CGA as a promising senotherapeutic nutraceutical able to reduce adipocyte senescence and its metabolic consequences, offering novel insights for the development of dietary supplements targeting age-related cellular dysfunction.

## Linked entities

- **Genes:** Lam (Lamin) [NCBI Gene 33782], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596], BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581], TP53 (tumor protein p53) [NCBI Gene 7157], CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026], MAPK (mitogen activated kinase-like protein) [NCBI Gene 7446652], PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207], SLC2A4 (solute carrier family 2 member 4) [NCBI Gene 6517]
- **Chemicals:** Chlorogenic Acid (PubChem CID 1794427)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Slc2a4 (solute carrier family 2 (facilitated glucose transporter), member 4) [NCBI Gene 20528] {aka GT2, Glut-4, Glut4, twgy}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Bax (BCL2-associated X protein) [NCBI Gene 12028], Lmnb1 (lamin B1) [NCBI Gene 16906], Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Cdkn1a (cyclin dependent kinase inhibitor 1A) [NCBI Gene 12575] {aka CAP20, CDKI, CIP1, Cdkn1, P21, SDI1}
- **Diseases:** adipose tissue dysfunction (MESH:D018205), metabolic disorders (MESH:D008659), inflammation (MESH:D007249), insulin resistance (MESH:D007333)
- **Chemicals:** glucose (MESH:D005947), polyphenol (MESH:D059808), CGA (MESH:D002726)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12787804/full.md

## References

102 references — full list in the complete paper: https://tomesphere.com/paper/PMC12787804/full.md

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Source: https://tomesphere.com/paper/PMC12787804