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L-Ascorbic Acid Supplementation Enhances the Potential of Regenerative Therapy to Combat Skin Aging
L-Ascorbic Acid Supplementation Enhances the Potential of Regenerative Therapy to Combat Skin Aging
Taking place in the Postgraduate Hall, 3rd Floor, Udayana University Postgraduate Building, the Doctoral Program in Medical Sciences, Faculty of Medicine, Udayana University, held an open defense for a Research-Based Doctoral Promotion (Research) with Dr. Komang Ardi Wahyuningsih, M.Biomed., for her dissertation entitled "Optimization of the Secretome of Mesenchymal Stem Cells in Adipose Tissue Supplemented with L-Ascorbic Acid: Evaluation of Anti-Aging Effects on the Skin of D-Galactose-Induced Aging Model Mice." (August 12, 2025)
The skin, as the outermost layer of the body, is constantly exposed to both extrinsic and intrinsic factors. These factors include genetic and metabolic influences that contribute to thinning, dryness, and wrinkling, accompanied by dermal atrophy. Anti-Aging Medicine (AAM) is a new medical discipline that studies the aging process, including skin aging, which generally begins gradually around the age of 25. L-ascorbic acid (LAA), recognized as a promising anti-aging agent, was used in this study.
The methods used were in vitro and in vivo studies. The in vitro study tested the optimal LAA dose on Adipose Tissue Mesenchymal Stem Cell (AT-MSC) cultures, which could stimulate proliferation, prevent senescence, and increase the secretion of growth factors and cytokines that play a role in skin aging. The in vitro study continued after two optimal LAA doses were identified to increase proliferation and prevent senescence of AT-MSCs without altering the characteristics of the cells. After the two optimal doses, 100 and 200 µg/mL, were found, the test continued to compare the two doses on proliferation, viability, morphology, characteristics, and secretion of IGF-1, TGF-ß, and IL-6.
In vitro studies have found that the optimal LAA supplementation dose for AT-MSC-derived secretome for in vivo testing in treating skin aging in a D-galactose-induced mouse model, based on its ability to increase proliferation, maintain viability, morphology, characteristics, and secretion of IGF-1, TGF-ß, and IL-6 from AT-MSCs, is 100 µg/mL.
The in vivo study was conducted in a Sprague Dawley rat model induced by aging with D-galactose injected subcutaneously for 8 weeks at a dose of 1000 mg/kgBW (15%). The rats were divided into five treatment groups: a non-aging control group, an aging control group, aging rats treated with AT-MSC secretome, aging rats treated with AT-MSC secretome supplemented with 100 µg/mL LAA, and aging rats treated with AT-MSC secretome combined with 20% LAA. The treatment consisted of weekly subcutaneous injections for four weeks.
The results showed a significant increase in epidermal thickness in all groups treated with AT-MSC secretome compared to the control group, with no significant differences between treatment groups. Although epidermal thickness increased in the treatment group, this increase did not occur in the dermis. Dermis thickness, total collagen, and the number of dermal papillae showed no significant differences compared to the untreated group.
This study also identified the levels of collagen type 1 (Col-1), SOD, and IL-6 in mouse skin tissue. The group receiving the combination of LAA and secretome showed the highest SOD concentration, while IL-6 production in the LAA-supplemented secretome was also higher than in the other groups. Collagen type 1 in the aging treatment group was higher than in the non-aging group, but lower than in the aging control group. This likely occurred because aging induction was stopped when the treatment injections began, allowing spontaneous regeneration in the aging control group. However, further research is needed to identify the type and structure of collagen produced in the treatment group compared to the control group. The control group is expected to have a better type of collagen with a more organized structure.
In conclusion, the secretome derived from AT-MSCs supplemented with LAA at a dose of 100 µg/mL shows potential as a therapeutic candidate in regenerative medicine, particularly for treating skin aging. To achieve optimal results, a longer treatment period is required for the aging model used.
The examination was officially opened by the Vice Dean for Academic and Planning of the Faculty of Medicine, Udayana University, Prof. Dr. dr. I Gede Eka Wiratnaya, S.Sp.OT(K). Prof. Eka expressed his appreciation and congratulations on the success of Dr. Komang Ardi Wahyuningsih, M.Biomed., in completing her doctoral studies. He also expressed his hope that the results of this research will not stop here but will develop further to produce products that benefit the wider community.
The examination was led by the Vice Dean for Academic and Planning, Prof. Dr. dr. I Gede Eka Wiratnaya, Sp.OT(K). The examination team included:
1. Prof. Dr. dr. I Gede Eka Wiratnaya, Sp.OT(K) (Promoter)
2. Prof. Dr. dr. I Wayan Weta, MS., Sp.GK (Co-Promoter I)
3. Prof. Dr. dr. I Gde Raka Widiana, Sp.PD-KGH (Co-Promoter II)
Academic Invitees:
1. Prof. Dr. dr. I Wayan Putu Sutirta Yasa, M.Si
2. Dr. dr. Ida Ayu Ika Wahyuniari, M.Kes
3. Dr. dr. I Made Muliarta, S.Ked., M.Kes
4. Dr. dr. Veronika Maria Sidharta, M.Biomed
During this examination, Dr. dr. Komang Ardi Wahyuningsih, M.Biomed., was declared the 470th Doctoral Graduate of the Doctoral Program in Medical Sciences, Faculty of Medicine, Udayana University, with Cum Laude honors.
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UDAYANA UNIVERSITY