Naughton Gail K, Jiang Lily I, Makino Elizabeth T, Chung Robin, Nguyen Audrey, Cheng Tsing, Kadoya Kuniko, Mehta Rahul C
Histogen, Inc., San Diego, CA, USA.
SGS Stephens, Richardson, TX, USA.
Dermatol Ther (Heidelb). 2023 Jan;13(1):169-186. doi: 10.1007/s13555-022-00839-2. Epub 2022 Nov 14.
The aging process involves numerous biological mechanisms that have been characterized and proposed as the "hallmarks of aging." Targeting the processes and pathways related to these hallmarks of aging that cause and promote skin aging could provide anti-aging benefits. A novel topical growth factor-based skin care serum (A+) was developed using human fibroblast conditioned media. This study aimed to assess the effects of A+ on four hallmarks of aging and its clinical efficacy in skin rejuvenation in subjects with moderate to severe overall facial photodamage.
Preclinical studies included immunohistochemistry in human ex vivo skin, and gene expression analysis in human 3D skin models. A 24-week, vehicle placebo-controlled study, including FaceQ patient-reported outcomes and skin biopsy analysis, was performed to assess clinical efficacy and tolerability.
Treatment with A+ resulted in reduced expression of cell senescence biomarker H2A.J and upregulation of genes associated with proteasome, autophagy, stemness, and intercellular communication. Clinical assessments showed A+ provided significantly greater reductions in sagging, coarse lines/wrinkles, fine lines/wrinkles, overall photodamage, and overall hyperpigmentation compared with placebo. Subjects felt they appeared younger-looking, reporting a median decrease in self-perceived age of 6 years after 12 weeks of use. Decreased levels of H2A.J and increased expression of key dermal extracellular matrix and epidermal barrier components, including collagen and elastin, were observed in skin biopsy samples.
The present study shows for the first time the potential effects of a topical growth factor-based cosmeceutical on cellular processes related to four hallmarks of aging (cellular senescence, loss of proteostasis, stem cell exhaustion, and altered intercellular communication) to help delay the aging process and restore aged skin. A+ targets the biological mechanisms underlying the aging process itself and stimulates skin regeneration, resulting in rapid and significant clinical improvements.
衰老过程涉及众多已被表征并被提议作为“衰老标志”的生物学机制。针对与导致和促进皮肤衰老的这些衰老标志相关的过程和途径进行干预,可能带来抗衰效果。一种基于新型局部生长因子的护肤精华液(A+)利用人成纤维细胞条件培养基研发而成。本研究旨在评估A+对衰老的四个标志的影响及其在中重度全脸光损伤受试者皮肤年轻化方面的临床疗效。
临床前研究包括人离体皮肤的免疫组织化学以及人三维皮肤模型的基因表达分析。开展了一项为期24周、以赋形剂为对照的安慰剂对照研究,包括使用面部质量问卷(FaceQ)进行患者报告结局评估以及皮肤活检分析,以评估临床疗效和耐受性。
使用A+治疗导致细胞衰老生物标志物H2A.J的表达降低,以及与蛋白酶体、自噬、干性和细胞间通讯相关基因的上调。临床评估显示,与安慰剂相比,A+在改善皮肤松弛、粗纹/皱纹、细纹/皱纹、整体光损伤和整体色素沉着方面有显著更大的效果。受试者感觉自己看起来更年轻,报告称使用12周后自我感知年龄中位数下降了6岁。在皮肤活检样本中观察到H2A.J水平降低,以及包括胶原蛋白和弹性蛋白在内的关键真皮细胞外基质和表皮屏障成分的表达增加。
本研究首次表明,一种基于局部生长因子的药妆品对与衰老的四个标志(细胞衰老、蛋白质稳态丧失、干细胞耗竭和细胞间通讯改变)相关的细胞过程具有潜在影响,有助于延缓衰老过程并恢复老化皮肤。A+针对衰老过程本身的生物学机制,刺激皮肤再生,从而带来快速且显著的临床改善。