Regulation of ENPP5, a senescence-associated secretory phenotype factor, prevents skin aging.

IF 4.4 4区 医学 Q1 GERIATRICS & GERONTOLOGY Biogerontology Pub Date : 2024-06-01 Epub Date: 2024-03-04 DOI:10.1007/s10522-024-10096-9
Kento Takaya, Kazuo Kishi
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Abstract

Aging negatively affects the appearance and texture of the skin owing to the accumulation of senescent fibroblasts within the dermis. Senescent cells undergo abnormal remodeling of collagen and the extracellular matrix through an inflammatory histolytic senescence-associated secretory phenotype (SASP). Therefore, suppression of SASP in senescent cells is essential for the development of effective skin anti-aging therapies. Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5), an extracellular signaling molecule, has been implicated in vascular aging and apoptosis; however, its role in SASP remains unclear. Therefore, this study aimed to investigate the role of ENPP5 in SASP and skin aging using molecular techniques. We investigated the effects of siRNA-mediated ENPP5 knockdown, human recombinant ENPP5 (rENPP5) treatment, and lentiviral overexpression of ENPP5 on SASP and aging in human skin fibroblasts. Additionally, we investigated the effect of siRNA-mediated ENPP5 knockdown on the skin of C57BL/6 mice. We found that ENPP5 was significantly expressed in replication-aged and otherwise DNA-damaged human skin fibroblasts and that treatment with human rENPP5 and lentiviral overexpression of ENPP5 promoted SASP and senescence. By contrast, siRNA-mediated knockdown of ENPP5 suppressed SASP and the expression of skin aging-related factors. Additionally, ENPP5 knockdown in mouse skin ameliorated the age-related reduction of subcutaneous adipose tissue, the panniculus carnosus muscle layer, and thinning of collagen fibers. Conclusively, these findings suggest that age-related changes may be prevented through the regulation of ENPP5 expression to suppress SASP in aging cells, contributing to the development of anti-aging treatments for the skin.

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调节衰老相关分泌表型因子 ENPP5 可防止皮肤老化。
由于真皮层中衰老成纤维细胞的积累,衰老会对皮肤的外观和质地产生负面影响。衰老细胞通过炎性组织溶解性衰老相关分泌表型(SASP)对胶原蛋白和细胞外基质进行异常重塑。因此,抑制衰老细胞的 SASP 对于开发有效的皮肤抗衰老疗法至关重要。八核苷酸焦磷酸酶/磷酸二酯酶家族成员 5(ENPP5)是一种细胞外信号分子,与血管衰老和细胞凋亡有关;但它在 SASP 中的作用仍不清楚。因此,本研究旨在利用分子技术研究 ENPP5 在 SASP 和皮肤老化中的作用。我们研究了 siRNA 介导的 ENPP5 敲除、人重组 ENPP5(rENPP5)处理和慢病毒过表达 ENPP5 对人类皮肤成纤维细胞 SASP 和衰老的影响。此外,我们还研究了 siRNA 介导的 ENPP5 基因敲除对 C57BL/6 小鼠皮肤的影响。我们发现,ENPP5 在复制老化和其他 DNA 损伤的人类皮肤成纤维细胞中明显表达,用人类 rENPP5 和慢病毒过表达 ENPP5 可促进 SASP 和衰老。相比之下,siRNA 介导的 ENPP5 敲除抑制了 SASP 和皮肤衰老相关因子的表达。此外,在小鼠皮肤中敲除ENPP5还能改善与年龄相关的皮下脂肪组织减少、肉垂肌层和胶原纤维变细等现象。这些研究结果表明,通过调节ENPP5的表达来抑制衰老细胞中的SASP,可以防止与年龄有关的变化,从而有助于开发皮肤抗衰老疗法。
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来源期刊
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
期刊介绍: The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.
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