Combined Effects of Tripeptide-3 and Hexapeptide-9 in Activating AMPKα to Inhibit D-Galactose-Induced Human Dermal Fibroblast Senescence
- 1Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, No. 4221, Xiang’an South Road, Xiamen 361102, China
- 2Xiamen 943 Cosmetics Co., Ltd., No. 363 Shangtang Community, Neicuo Town, Xiang’an District, Xiamen 361101, China
- 3Pur Source (Guangdong) Life Science Research Co., Ltd., No. 173 Yingbin Avenue, Huadu District, Guangzhou 510800, China
Abstract
Dermatological senescence, characterized by functional deterioration and the accumulation of senescent fibroblasts, has prompted the investigation of safe and effective anti-ageing agents. The present study investigates the role of Tripeptide-3 (T-3) and Hexapeptide-9 (H-9) in countering D-galactose-induced senescence in human dermal fibroblasts (HDFs). Using a D-gal-induced senescence model, we found that non-cytotoxic concentrations of T-3 and H-9, both individually and in combination, led to a substantial reduction in senescence-associated β-galactosidase activity and concomitant downregulation of p21 expression. Notably, the combination exhibited superior anti-senescence effects. Mechanistically, both peptides activated the AMPKα pathway by increasing phosphorylation at Thr172, with their combination showing enhanced activation. It is of particular significance that the AMPKα inhibitor Compound C served to nullify these protective effects, thereby establishing AMPKα activation as a critical contributing pathway in the combined anti-senescence effect of T-3 and H-9. This study provides novel evidence that T-3 and H-9 inhibit fibroblast senescence via AMPKα activation, thus providing a mechanistic basis for the development of peptide-based anti-ageing skincare formulations.
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BibTeX
@article{cao2026combined,
title = {{Combined Effects of Tripeptide-3 and Hexapeptide-9 in Activating AMPKα to Inhibit D-Galactose-Induced Human Dermal Fibroblast Senescence}},
author = {Yuan Cao and Jun Wang and Yongkuan Pan and Liming Hou and Yan Jin and Changwei Cai and Fuquan Jiang and Quan-Cheng Chen},
journal = {Cosmetics},
year = {2026},
month = sep,
doi = {10.3390/cosmetics13050238},
url = {https://doi.org/10.3390/cosmetics13050238},
note = {CC BY},
}
RIS
TY - JOUR
TI - Combined Effects of Tripeptide-3 and Hexapeptide-9 in Activating AMPKα to Inhibit D-Galactose-Induced Human Dermal Fibroblast Senescence
AU - Yuan Cao
AU - Jun Wang
AU - Yongkuan Pan
AU - Liming Hou
AU - Yan Jin
AU - Changwei Cai
AU - Fuquan Jiang
AU - Quan-Cheng Chen
PY - 2026
DA - 2026/09/01
JO - Cosmetics
DO - 10.3390/cosmetics13050238
UR - https://doi.org/10.3390/cosmetics13050238
AB - Dermatological senescence, characterized by functional deterioration and the accumulation of senescent fibroblasts, has prompted the investigation of safe and effective anti-ageing agents. The present study investigates the role of Tripeptide-3 (T-3) and Hexapeptide-9 (H-9) in countering D-galactose-induced senescence in human dermal fibroblasts (HDFs). Using a D-gal-induced senescence model, we found that non-cytotoxic concentrations of T-3 and H-9, both individually and in combination, led to a substantial reduction in senescence-associated β-galactosidase activity and concomitant downregulation of p21 expression. Notably, the combination exhibited superior anti-senescence effects. Mechanistically, both peptides activated the AMPKα pathway by increasing phosphorylation at Thr172, with their combination showing enhanced activation. It is of particular significance that the AMPKα inhibitor Compound C served to nullify these protective effects, thereby establishing AMPKα activation as a critical contributing pathway in the combined anti-senescence effect of T-3 and H-9. This study provides novel evidence that T-3 and H-9 inhibit fibroblast senescence via AMPKα activation, thus providing a mechanistic basis for the development of peptide-based anti-ageing skincare formulations.
SN - 2079-9284
ER -