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Updated: Aug 28, 2025
Induction and Validation of Cellular Senescence in Primary Human Cells
Published on: June 20, 2018
Grp94 Inhibitor HCP1 Inhibits Human Dermal Fibroblast Senescence
Xiaoling Cui1, Xuxiao Hao1, Jie Wen2
1Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao 266237, China.
Abstract:
Researchers are paying more and more attention to aging, especially skin aging. Therefore, it is urgent to find an effective way to inhibit aging. Here, we report a small chemical molecule, HCP1, that inhibited the senescence of human dermal fibroblasts (HDFs). First, we performed morphological experiment and found that HCP1-treated HDFs were no longer elongated and flat compared to DMSO-treated groups. Next, we found that the number of β-gal positive cells decreased compared to DMSO-treated groups. Through flow cytometry, western blot, and immunofluorescence, we found that HCP1 could inhibit the senescence of HDFs. In the study of the mechanism, we found that HCP1 could regulate the AMPK/mTOR signal pathway through glucose-regulated protein 94 (Grp94). In addition, we found that HCP1 could promote the interaction between Grp94 and lysosomes, which led to an increase in the activity of lysosomes and inhibited the senescence of HDFs. At the same time, we found that HCP1 decreased the concentration of Ca2+ in mitochondria, inhibiting the senescence of HCP1. Therefore, we propose that HCP1 is a potential aging-inhibiting compound, and provide a new idea for the development of senescence-inhibiting drugs.
Insights
Researchers discovered HCP1, a novel chemical compound that effectively inhibits skin aging in human dermal fibroblasts. This molecule regulates cellular pathways and lysosomal activity, offering a promising new avenue for anti-aging drug development.
Area of Science:
- Biogerontology
- Dermatology
- Molecular Biology
Background:
- Skin aging is a growing concern, necessitating effective interventions.
- Cellular senescence, particularly in human dermal fibroblasts (HDFs), is a key aspect of skin aging.
Purpose of the Study:
- To investigate the anti-aging potential of a novel small chemical molecule, HCP1.
- To elucidate the underlying molecular mechanisms by which HCP1 inhibits HDF senescence.
Main Methods:
- Morphological analysis and senescence-associated β-galactosidase staining.
- Flow cytometry, Western blot, and immunofluorescence assays.
- Investigation of the AMPK/mTOR pathway, Grp94 interactions, lysosomal activity, and mitochondrial Ca2+ levels.
Main Results:
- HCP1 treatment reversed HDF morphological changes and reduced β-gal positive cells.
- HCP1 inhibited HDF senescence through regulating the AMPK/mTOR pathway via Grp94.
- HCP1 enhanced lysosomal activity and decreased mitochondrial Ca2+ concentration, collectively inhibiting senescence.
Conclusions:
- HCP1 demonstrates significant potential as an anti-aging compound by inhibiting HDF senescence.
- The study provides novel insights into the mechanisms of aging inhibition, involving Grp94, lysosomes, and mitochondrial calcium.
- HCP1 represents a promising candidate for the development of new senescence-inhibiting drugs.
Related Concept Videos
01:12Renewal of Skin Epidermal Stem Cells
02:15Replicative Cell Senescence