Yijia Zhang1 | Xueer Wang1 | Jianyuan Huang1 | Xinyue Zhang1 | Lingwei Bu1 |

Yarui Zhang1 | Fengting Liang1 | Shenhua Wu1 | Min Zhang1 | Lu Zhang2 |

Lin Zhang1

1 GDMPA Key Laboratory of key Technologies for Cosmetics Safety and Efficacy Evaluation, NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

2 Guangdong Provincial Key Laboratory of Proteomics, Department of Pathophysiology, Key Laboratory of Mental Health of the Ministry of Education, School of Basic Medical Sciences, Center for Orthopaedic Surgery of the Third Affiliated Hospital, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, China

Correspondence

Lu Zhang, Guangdong Provincial Key Laboratory of Proteomics, Department of Pathophysiology, Key Laboratory of Mental Health of the Ministry of Education, School of Basic Medical Sciences, Center for Orthopaedic Surgery of the Third Affiliated Hospital, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, China.

Email: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 Lin Zhang, GDMPA Key Laboratory of key Technologies for Cosmetics Safety and Efficacy Evaluation, NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

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Funding information

National Natural Science Foundation of China, Grant/Award Number: 82073417, 81872514 and 81971297; GDMPA Key Laboratory Project of Scientific and Technological Innovation, Grant/Award

Number: 2023ZDZ12; Guangdong Basic and Applied Basic Research Foundation, Grant/Award Number: 2022A1515010768, 2023A1515012480 and 2024A121301233

Abstract

Skin aging has been associated with the onset of various skin issues, and recent studies have identified an increase in Cdc42 activity in naturally aging mice. While previous literature has suggested that CASIN, a specific inhibitor of Cdc42 activity, may possess anti-aging properties, its specific effects on the epidermis and dermis, as well as the underlying mechanisms in naturally aging mice, remain unclear. Our study revealed that CASIN demonstrated the ability to increase epidermal and dermal thickness, enhance dermal-epidermal junction, and stimulate collagen and elastic fiber synthesis in 9-, 15-, and 24-month-old C57BL/6 mice in vivo. Moreover, CASIN was found to enhance the proliferation, differentiation, and colony formation and restore the cytoskeletal morphology of primary keratinocytes in naturally aging skin in vitro. Furthermore, the anti-aging properties of CASIN on primary fibroblasts in aging mice were mediated by the ribosomal protein RPL4 using proteomic sequencing, influencing collagen synthesis and cytoskeletal morphology both in vitro and in vivo. Meanwhile, both subcutaneous injection and topical application exhibited anti-aging effects for a duration of 21 days. Additionally, CASIN exhibited anti-inflammatory properties, while reduced expression of RPL4 was associated with increased inflammation in the skin of naturally aging mice. Taken together, our results unveil a novel function of RPL4 in skin aging, providing a foundational basis for future investigations into ribosomal proteins. And CASIN shows promise as a potential anti-aging agent for naturally aging mouse skin, suggesting potential applications in the field.

KEYWORDS

CASIN, Cdc42, fibroblast, keratinocyte, ribosome, skin aging