Division of Geriatrics and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21228, USA; Department of Oncology, Johns Hopkins University School of Medicine, 1650 Orleans Street, MD 21287, USA.
Exp Gerontol. 2022 Aug;165:111835. doi: 10.1016/j.exger.2022.111835. Epub 2022 May 19.
Collagen is a major component of the skin's support system, allowing for its firmness, elasticity, and mechanical strength. Skin collagen production decreases as we age and is associated with increased sagging, wrinkling, and thinning. The Renin-Angiotensin System (RAS) is a key hormonal system that changes with age and affects multiple organ systems. The primary health benefits of Angiotensin (Ang) receptor type1 (ATR) blockers are believed to arise from systemic effects on blood pressure. However, there is also a skin-specific RAS, though this system has been less well characterized. There are eight FDA-approved angiotensin receptor blockers (ARBs) on the market, although the impact of topical ARBs on aging skin is unknown. Here, we evaluated the topical penetration of gel formulations of eight ARBs using human cadaver skin. Our results show that valsartan achieved the highest skin penetration compared to other ARBs. We then treated human skin fibroblasts from 2-year-old and 57-year-old individuals with valsartan alone or in combination with the neprilysin inhibitor sacubitril. Sacubitril works synergistically with valsartan by inhibiting the degradation of angiotensin II, thereby increasing its bioavailability. Treatment of young and older adult human skin cells with valsartan and sacubitril led to a five-fold increase in collagen type-1 production in the young cells and a four-fold increase in collagen type-1 in older adult cells. This study demonstrates a potential novel application for the widely prescribed drug combination sacubitril-valsartan as a topical agent in aged skin.
胶原蛋白是皮肤支撑系统的主要组成部分，使其具有坚固性、弹性和机械强度。随着年龄的增长，皮肤胶原蛋白的产生减少，与皮肤松弛、皱纹和变薄有关。肾素-血管紧张素系统（RAS）是一个关键的激素系统，随着年龄的增长而变化，影响多个器官系统。血管紧张素（Ang）受体 1 型（ATR）阻滞剂的主要健康益处被认为是源于对血压的全身影响。然而，也有一个皮肤特异性的 RAS，尽管这个系统还没有得到很好的描述。市场上有八种获得 FDA 批准的血管紧张素受体阻滞剂（ARB），尽管局部 ARB 对衰老皮肤的影响尚不清楚。在这里，我们使用人体尸体皮肤评估了八种 ARB 的凝胶制剂的经皮渗透。我们的结果表明，缬沙坦与其他 ARB 相比，皮肤渗透度最高。然后，我们用缬沙坦单独或与 Neprilysin 抑制剂沙库巴曲联合处理来自 2 岁和 57 岁个体的人皮肤成纤维细胞。沙库巴曲通过抑制血管紧张素 II 的降解与缬沙坦协同作用，从而增加其生物利用度。用缬沙坦和沙库巴曲处理年轻和成年人大人皮肤细胞，导致年轻细胞中胶原蛋白 1 型的产生增加五倍，成年人大人细胞中胶原蛋白 1 型的产生增加四倍。这项研究表明，广泛应用的药物组合沙库巴曲缬沙坦作为一种在老年皮肤中的局部制剂具有潜在的新应用。
