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Updated: Jul 30, 2026
Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Glutaminase inhibitors rejuvenate human skin via clearance of senescent cells: a study using a mouse/human chimeric
Kento Takaya1, Tatsuyuki Ishii1, Toru Asou1
1Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, Japan.
Abstract:
Skin aging caused by various endogenous and exogenous factors results in structural and functional changes to skin components. However, the role of senescent cells in skin aging has not been clarified. To elucidate the function of senescent cells in skin aging, we evaluated the effects of the glutaminase inhibitor BPTES (bis-2-(5-phenylacetamido-1, 3, 4-thiadiazol-2-yl)ethyl sulfide) on human senescent dermal fibroblasts and aged human skin. Here, primary human dermal fibroblasts (HDFs) were induced to senescence by long-term passaging, ionizing radiation, and treatment with doxorubicin, an anticancer drug. Cell viability of HDFs was assessed after BPTES treatment. A mouse/human chimeric model was created by subcutaneously transplanting whole skin grafts from aged humans into nude mice. The model was treated intraperitoneally with BPTES or vehicle for 30 days. Skin samples were collected and subjected to reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, and histological analysis. BPTES selectively eliminated senescent dermal fibroblasts regardless of the method used to induce senescence; aged human skin grafts treated with BPTES exhibited increased collagen density, increased cell proliferation in the dermis, and decreased aging-related secretory phenotypes, such as matrix metalloprotease and interleukin. These effects were maintained in the grafts 1 month after termination of the treatment. In conclusion, selective removal of senescent dermal fibroblasts can improve the skin aging phenotype, indicating that BPTES may be an effective novel therapeutic agent for skin aging.
Insights
The glutaminase inhibitor BPTES selectively removes senescent dermal fibroblasts, improving aged skin characteristics like collagen density and reducing aging markers. This suggests BPTES as a potential therapeutic for skin aging.
Area of Science:
- Dermatology
- Cell Biology
- Gerontology
Background:
- Skin aging involves structural and functional changes due to endogenous and exogenous factors.
- The specific role of senescent cells in skin aging remains unclear.
- Senescent cells contribute to aging phenotypes through various mechanisms.
Purpose of the Study:
- To investigate the function of senescent cells in skin aging.
- To evaluate the effects of the glutaminase inhibitor BPTES on senescent human dermal fibroblasts and aged human skin.
- To determine if BPTES can ameliorate skin aging phenotypes.
Main Methods:
- Human dermal fibroblasts (HDFs) were induced into senescence using long-term passaging, ionizing radiation, or doxorubicin treatment.
- Cell viability was assessed post-BPTES treatment.
- A mouse/human chimeric model with aged human skin grafts was treated with BPTES or vehicle.
- Skin samples underwent RT-qPCR, western blotting, and histological analysis.
Main Results:
- BPTES selectively eliminated senescent HDFs irrespective of the induction method.
- Aged human skin grafts treated with BPTES showed increased collagen density and dermal cell proliferation.
- BPTES treatment decreased aging-related secretory phenotypes, including matrix metalloproteinase and interleukin levels.
- These improvements persisted for one month after BPTES treatment cessation.
Conclusions:
- Selective elimination of senescent dermal fibroblasts can significantly improve the skin aging phenotype.
- BPTES demonstrates potential as a novel therapeutic agent for combating skin aging.
- Targeting senescent cells offers a promising strategy for anti-aging interventions.
