eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2025-03-31 18 1 713 720 10.13005/bpj/3122 65020 article Komang Ardi Wahyuningsih 1 Veronika Maria Sidharta 1 Ecie Budiyanti 1 Retnaningtyas Siska Dianty 1 Department of Histology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, South Jakarta, Jakarta, Indonesia Skin aging occurs due to gene mutation or hormonal factors called intrinsic factors. Mechanisms of glycation, free radicals, and other cellular and molecular mechanisms can cause dermal atrophy and decreased collagen. The secretome of stem cells, which consists of many growth factors and ascorbic acid, can stimulate cell proliferation and increase the production of intracellular matrixes. This property is well-known for its antioxidant activity in eradicating the accumulation of free radicals contributing to skin aging. This study will observe the role of secretome and ascorbic acid combination in increasing the antioxidant levels and type 1 collagen production in the intrinsic skin aging rat model. Thirty male Sprague Dawley rats were divided into five groups consisting of the nonaging control group; the intrinsic aging control group, which was injected with 1000 mg/kg BW of 15% D-Galactose; three intrinsic aging groups treated with secretome only, ascorbic acid only, or a combination of both. After 4 weeks of treatment, all skin tissue was collected and divided to examine dermal thickness, Super Oxide Dismutase (SOD), dan type 1 collagen using Enzyme-Linked Immunosorbent Assay (ELISA). Data were analyzed statistically. All treatment groups show a significant difference compared to the control group across all parameters. An enhancement with secretome-only injection was observed in all examinations, showing a significant difference (p<0.05) compared to the intrinsic aging in dermal thickness and also non-aging control groups for SOD and type 1 collagen concentration parameters. Both secretome and ascorbic acid or one another can be used for skin aging treatment. Even though the secretome only gave better results, this combination's dose, application method, optimization, and time need further study.   https://biomedpharmajournal.org/vol18no1/the-combination-of-mesenchymal-stem-cell-msc-secretome-and-vitamin-c-has-a-promising-effect-in-treating-skin-aging-as-it-is-not-significantly-different-from-secretome-or-vitamin-c-alone-compared-t/ Antioxidant Ascorbic acid Proliferation Secretome Skin aging Stem cell