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Updated: Sep 23, 2025

Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Isatis tinctoria L. Leaf Extract Inhibits Replicative Senescence in Dermal Fibroblasts by Regulating mTOR-NF-κB-SASP
Jieun Woo1, Seoungwoo Shin1, Hyanggi Ji1
1BioSpectrum Life Science Institute, 767, Sinsu-ro, Yongin-si 16827, Korea.
Abstract:
Senescent fibroblasts progressively deteriorate the functional properties of skin tissue. Senescent cells secrete senescence-associated secretory phenotype (SASP) factor, which causes the aging of surrounding non-senescent cells and accelerates aging in the individuals. Recent findings suggested the senomorphic targeting of the SASP regulation as a new generation of effective therapeutics. We investigated whether Isatis tinctoria L. leaf extract (ITE) inhibited senescence biomarkers p53, p21, and p16 gene expression, and SASP secretions by inhibiting cellular senescence in the replicative senescent human dermal fibroblast (RS-HDF). ITE has been demonstrated to inhibit the secretion of SASP factors in several senomorphic types by regulating the MAPK/NF-κB pathway via its inhibitory effect on mTOR. ITE suppressed the inflammatory response by inhibiting mTOR, MAPK, and IκBα phosphorylation, and blocking the nuclear translocation of NF-κB. In addition, we observed that autophagy pathway was related to inhibitory effect of ITE on cellular senescence. From these results, we concluded that ITE can prevent and restore senescence by blocking the activation and secretion of senescence-related factors generated from RS-HDFs through mTOR-NF-κB regulation.
Insights
Isatis tinctoria L. leaf extract (ITE) combats skin aging by inhibiting senescence-associated secretory phenotype (SASP) factors. This senomorphic approach targets the mTOR-NF-κB pathway, reducing inflammation and restoring skin health.
Area of Science:
- Dermatology and Cellular Biology
- Aging Research
- Pharmacology
Background:
- Cellular senescence, characterized by senescence-associated secretory phenotype (SASP) factors, drives skin aging.
- Targeting SASP regulation represents a novel therapeutic strategy for aging.
- Senescent fibroblasts impair skin tissue function.
Purpose of the Study:
- To investigate the senomorphic effects of Isatis tinctoria L. leaf extract (ITE) on human dermal fibroblasts.
- To determine if ITE inhibits senescence biomarkers (p53, p21, p16) and SASP secretions.
- To elucidate the molecular pathways targeted by ITE in cellular senescence.
Main Methods:
- Assessed ITE's impact on senescence biomarkers (p53, p21, p16) gene expression in replicative senescent human dermal fibroblasts (RS-HDF).
- Quantified SASP factor secretion inhibition by ITE.
- Investigated ITE's effects on the mTOR, MAPK, and NF-κB signaling pathways, including protein phosphorylation and nuclear translocation.
- Explored the role of the autophagy pathway in ITE's anti-senescence activity.
Main Results:
- ITE effectively inhibited the expression of senescence biomarkers p53, p21, and p16.
- ITE suppressed the secretion of SASP factors from RS-HDFs.
- ITE regulated the MAPK/NF-κB pathway by inhibiting mTOR, MAPK, and IκBα phosphorylation, and blocking NF-κB nuclear translocation.
- The autophagy pathway was implicated in ITE's inhibitory effect on cellular senescence.
Conclusions:
- ITE demonstrates senomorphic properties by preventing and restoring cellular senescence in human dermal fibroblasts.
- ITE acts through the regulation of the mTOR-NF-κB pathway to inhibit the activation and secretion of senescence-related factors.
- ITE holds potential as a therapeutic agent for age-related skin conditions by targeting cellular senescence and inflammation.
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