# Skin Depigmenting Agents in Anti-Aging Cosmetics: A Medicinal Perspective on Emerging Ingredients
## 4 Conclusions  
Being the most visible and exposed organ of the human body, skin reflects the aging process in humans promoted by environmental factors besides exhibiting signs of chronological aging. These changes manifest through wrinkles, loss of firmness, and hyper-pigmentation. Research and development of new anti-aging formulations started to focus on tackling the signs of chronological and photoaging, including skin hyperpigmentation. The active ingredients that lighten skin tone can either be natural or synthetic substances, and they may act at different levels of the melanogenesis process. The safety concern raised around depigmenting drugs such as hydroquinone and corticosteroids led to the search for alternative ingredients for cosmetic products, including the exploitation of previously used agents, since introducing a new ingredient can be a costly and time-consuming process. To date, the trends in the use of depigmenting agents in anti-aging cosmetics have not yet been unveiled. This study reports an increasing trend in the use of these ingredients, raising up to 74% in 2018. Although the top 12 presents several well-known depigmenting agents, this work focused on highlighting the novelties introduced in 2018. Alpha-hydroxy acids, niacinamide, ascorbic acid and derivatives, as well as retinol and derivatives have great popularity as depigmenting ingredients in anti-aging cosmetics and were consistently the most used throughout the period of analysis. Tranexamic acid, bakuchiol, and 4-butylresorcinol were only found in products launched or reformulated in 2018. The clinical studies proving the efficacy of these three ingredients in the reduction of senile hyperpigmentation are usually focused on the exploitation of mixtures containing several ingredients, which hinders the attribution of the studied effect to a specific ingredient. Studies reporting their mechanisms of action are well established; however, comparative studies concerning their depigmenting efficacy would be useful to highlight the most potent ingredients.  
Regarding their synthetic methodologies, advances in green processes were noted among their industrial production. Despite the three analyzed ingredients not being new ingredients, over the last few years, an upsurge was noticed in both reported methodologies for their synthesis at an industrial scale and in their incorporation into anti-aging cosmetics.  
Conceptualization: I.F.A.; Data collection: M.S.F.; Data analysis: D.I.S.P.R.; Writing--original draft preparation and final manuscript: D.I.S.P.R. and M.S.F.; Supervision: [PERSON]; Writing--review and editing: [PERSON] and E.S. All authors have read and agreed to the published version of the manuscript.  
**Funding:** This work is financed by national funds from FCT--Fundacao para a Ciencia e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences--UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy--i4 HB. This research was also supported by national funds through FCT (Foundation for Science and Technology) within the scope of UIDB/04423/2020, UIDP/04423/2020 (Group of Natural Products and Medicinal Chemistry--CIIMAR), as well as a structured program of R&D&I ATLANTIDA (NORTE-01-0145-FEDER-000040), supported by NORTE2020, through ERDF, and CHIRALBIO ACTIVE-PI-3 RL-INFACTS-2019.  
**Institutional Review Board Statement:** Not applicable.  
**Informed Consent Statement:** Not applicable.  
**Data Availability Statement:** Not applicable.  
**Conflicts of Interest:** The authors declare no conflict of interest.