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.

中文翻译：

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Grp94 抑制剂 HCP1 抑制人皮肤成纤维细胞衰老

研究人员越来越关注衰老，尤其是皮肤衰老。因此，寻找一种有效抑制衰老的方法迫在眉睫。在这里，我们报告了一种小化学分子 HCP1，它可以抑制人类皮肤成纤维细胞 (HDF) 的衰老。首先，我们进行了形态学实验，发现与 DMSO 处理组相比，HCP1 处理的 HDF 不再拉长和变平。接下来，我们发现与 DMSO 处理组相比，β-gal 阳性细胞的数量减少。通过流式细胞术、蛋白质印迹和免疫荧光，我们发现 HCP1 可以抑制 HDF 的衰老。在机制研究中，我们发现HCP1可以通过葡萄糖调节蛋白94（Grp94）调节AMPK/mTOR信号通路。此外，我们发现HCP1可以促进Grp94与溶酶体的相互作用，这导致溶酶体的活性增加并抑制HDF的衰老。同时，我们发现HCP1降低了Ca的浓度²⁺在线粒体中，抑制 HCP1 的衰老。因此，我们提出HCP1是一种潜在的抗衰老化合物，为开发抗衰老药物提供了新思路。