4,4'-Dimethoxychalcone protects the skin from AAPH-induced senescence and UVB-induced photoaging by activating
Yanpei Gu1, Jianxin Han1, Fan Xue1
1College of Biosystems Engineering and Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Center for Food Technology and Equipment, Zhejiang University, Hangzhou 310058, China. yzhang@zju.edu.cn.
Abstract:
Aging can lead to the occurrence of many degenerative diseases, and the most intuitive consequences are mainly manifested on the skin, which is affected by both endogenous and exogenous aging factors and can be used as an ideal model organ for studying aging. 4,4'-Dimethoxychalcone (DMC), a natural flavonoid compound from Angelica sinensis, has been proven to prolong the lifespan of multiple species. However, it is not clear whether it has the effect of delaying skin aging. This study aimed to establish a skin senescent cell model induced by oxidative stress, and further, to analyze the inhibitory effect of DMC on cellular senescence, and explore its molecular mechanisms. We found that treatment of HaCaT cells with 1 mM 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) for 48 h showed significant senescent characteristics, which could be effectively alleviated by pretreatment with the antioxidant N-acetyl-L-cysteine (NAC). DMC significantly inhibited AAPH-induced senescence, and further mechanism studies showed that the activation of autophagy which depended on the phosphorylation of ULK1 at Ser555 was necessary for DMC to alleviate senescence of HaCaT cells. In addition, the mitogen-activated protein kinase (MAPK) signal pathway was also involved in the regulation of autophagy induced by DMC. These results were also validated in UVB-induced photoaging mice. In conclusion, we successfully establish a skin senescent cell model and prove that DMC can be used as a potential therapeutic agent to intervene in skin aging.
Insights
4,4'-Dimethoxychalcone (DMC), a natural compound, effectively delays skin aging by inhibiting oxidative stress-induced cellular senescence. It activates autophagy via ULK1 phosphorylation, offering a potential therapeutic for skin aging.
Area of Science:
- Dermatology
- Cellular Biology
- Biochemistry
Background:
- Skin aging results from endogenous and exogenous factors.
- Cellular senescence is a key hallmark of aging skin.
- Natural compounds are explored for anti-aging interventions.
Purpose of the Study:
- To establish an oxidative stress-induced skin senescent cell model.
- To investigate the anti-senescence effects of 4,4'-Dimethoxychalcone (DMC).
- To elucidate the molecular mechanisms underlying DMC's action on skin aging.
Main Methods:
- Induced skin senescence in HaCaT cells using 2,2 ac-azobis(2-methylpropionamidine) dihydrochloride (AAPH).
- Assessed DMC's inhibitory effect on AAPH-induced cellular senescence.
- Analyzed autophagy activation (ULK1 phosphorylation) and MAPK signaling pathway involvement.
- Validated findings in UVB-induced photoaging mouse models.
Main Results:
- AAPH treatment successfully induced significant senescent characteristics in HaCaT cells.
- DMC pretreatment significantly alleviated AAPH-induced skin cell senescence.
- DMC-mediated anti-senescence effects were dependent on autophagy activation via ULK1 phosphorylation.
- The mitogen-activated protein kinase (MAPK) pathway was implicated in DMC-induced autophagy.
Conclusions:
- Established a reliable model for studying skin senescence.
- Demonstrated DMC's potent anti-senescence properties in vitro and in vivo.
- Identified autophagy activation as a key mechanism for DMC's anti-aging effects.
- Positioned DMC as a promising therapeutic agent for mitigating skin aging.
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