Abstract
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 (AT(1)R) 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.