Navitoclax (ABT-263) Rejuvenates Human Skin by Eliminating Senescent Dermal Fibroblasts in a Mouse/Human Chimeric Model.

IF 2.2 4区医学 Q3 GERIATRICS & GERONTOLOGY

Rejuvenation research Pub Date : 2023-02-01 DOI:10.1089/rej.2022.0048

Kento Takaya, Tatsuyuki Ishii, Toru Asou, Kazuo Kishi

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引用次数: 3

Abstract

Chronic senescence, such as aging, contributes to age-related tissue dysfunction and disease development. The accumulation of senescent fibroblasts and the senescence-associated secretory phenotype is particularly implicated in this process. Removal of senescent cells has been reported to prevent tissue dysfunction and to extend the life span during aging. ABT-263 (navitoclax), which inhibits antiapoptotic proteins, is a leading antiaging drug; however, its role in human skin aging is unclear. This study aimed to determine the rejuvenating effects of ABT-263 on aging skin using a human skin graft mouse model. We assessed the viability of ABT-263-treated skin fibroblasts after inducing senescence. Aged human skin was transplanted under the back skin of nude mice and injected intraperitoneally with the drug or control. Analysis of the skin specimens revealed that ABT-263 induced selective elimination of senescent dermal fibroblasts. Senescent human skin treated with ABT-263 exhibited a decrease in the number of senescent cells and in the expression of aging-related secretory phenotype molecules, such as matrix metalloproteinases and interleukins and an increase in collagen density. Our results indicate that selective removal of senescent skin cells with ABT-263 can improve the aging phenotype of human skin without side effects. ABT-263 is, thus, a novel potential therapeutic agent for skin aging.

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在小鼠/人嵌合模型中，Navitoclax (ABT-263)通过消除衰老的真皮成纤维细胞使人皮肤恢复活力。

慢性衰老，如衰老，有助于年龄相关的组织功能障碍和疾病的发展。衰老成纤维细胞的积累和衰老相关的分泌表型在这一过程中尤为重要。据报道，清除衰老细胞可以防止组织功能障碍，延长衰老过程中的寿命。ABT-263 (navitoclax)，抑制抗凋亡蛋白，是一种领先的抗衰老药物;然而，它在人类皮肤老化中的作用尚不清楚。本研究旨在通过人类皮肤移植小鼠模型确定ABT-263对衰老皮肤的恢复作用。我们评估了abt -263处理的皮肤成纤维细胞在诱导衰老后的生存能力。将衰老的人皮肤移植到裸鼠背部皮下，并腹腔注射药物或对照组。对皮肤标本的分析表明，ABT-263诱导衰老的真皮成纤维细胞选择性消除。ABT-263处理后的衰老皮肤显示衰老细胞数量减少，衰老相关分泌表型分子(如基质金属蛋白酶和白细胞介素)的表达减少，胶原密度增加。我们的研究结果表明，ABT-263选择性去除衰老皮肤细胞可以改善人类皮肤的衰老表型，而且没有副作用。因此，ABT-263是一种新的潜在的皮肤衰老治疗剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Rejuvenation research 医学-老年医学

CiteScore

4.50

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Rejuvenation Research publishes cutting-edge, peer-reviewed research on rejuvenation therapies in the laboratory and the clinic. The Journal focuses on key explorations and advances that may ultimately contribute to slowing or reversing the aging process, and covers topics such as cardiovascular aging, DNA damage and repair, cloning, and cell immortalization and senescence. Rejuvenation Research coverage includes: Cell immortalization and senescence Pluripotent stem cells DNA damage/repair Gene targeting, gene therapy, and genomics Growth factors and nutrient supply/sensing Immunosenescence Comparative biology of aging Tissue engineering Late-life pathologies (cardiovascular, neurodegenerative and others) Public policy and social context.