Cosmeceuticals for Anti-Aging: Mechanisms, Clinical Evidence, and Regulatory Insights—A Comprehensive Review

Abstract

Products with biologically active ingredients have emerged as a powerful category within the skincare and anti-aging sectors. Bridging the gap between pharmaceuticals and cosmetics, they offer therapeutic benefits supported by scientific evidence while maintaining the esthetic appeal of traditional skincare. This review aims to provide a comprehensive overview of cosmeceuticals with a particular focus on their anti-aging potential. This review highlights recent advances in cosmeceutical actives. Next-generation retinoids such as hydroxypinacolone retinoate and retinyl retinoate show comparable efficacy to tretinoin with improved tolerability, though current studies are small and short-term. Peptides, including signal, carrier, and neurotransmission-inhibiting peptides, offer multifunctional effects on extracellular matrix remodeling and wrinkle reduction, with supportive but modest clinical evidence enhanced by nanocarrier delivery. Antioxidants, particularly vitamin C and coenzyme Q10, are supported by controlled trials showing improvements in photoprotection, mitochondrial function, and wrinkle depth, though data are limited by sample size and follow-up. Botanical polyphenols are gaining prominence: nanoparticle-encapsulated epigallocatechin gallate (EGCG) enhances anti-photoaging activity in preclinical studies; oral microencapsulated curcumin has shown visible benefits in nutricosmetic trials; and bakuchiol, a retinol-like meroterpene, demonstrated comparable efficacy to retinol with superior tolerability. Advances in delivery systems—including nanoemulsions, phospholipid complexes, and encapsulation technologies—improve stability, bioavailability, and skin penetration. In conclusion, retinoids, vitamin C, and AHAs/BHAs remain the most evidence-based actives, whereas newer bioactives and advanced formulations appear promising but require larger, long-term randomized trials to establish their role in dermatologic practice.

1. Introduction

The global demand for effective anti-aging skincare solutions has spurred remarkable innovation at the intersection of dermatology and cosmetics. Among these innovations, cosmeceuticals—a term first coined by Dr. Albert Kligman in the 1980s [1]—have become a cornerstone of the modern skincare industry. These hybrid products contain biologically active ingredients that purport to provide therapeutic benefits, such as wrinkle reduction, improved skin tone, and enhanced barrier function, without undergoing the same level of regulation as pharmaceutical drugs [2].

The anti-aging market segment dominates the cosmeceutical landscape, with estimates projecting a market value exceeding USD 50 billion by 2027 [3]. This growth is driven by an aging global population, increased consumer awareness of skin health, and a growing preference for evidence-based over-the-counter products [4]. Cosmeceuticals appeal to consumers seeking science-backed efficacy in formulations that remain accessible and user-friendly, drawing on research from dermatology, biochemistry, and pharmacology [5,6].

Despite their commercial success, cosmeceuticals occupy a regulatory gray area. Most regulatory bodies, including the U.S. Food and Drug Administration (FDA), do not legally recognize cosmeceuticals as a distinct category [7]. Products must be classified either as cosmetics or drugs, depending on the claims made. This regulatory ambiguity affects labeling, marketing, and the level of scientific validation required [8]. In contrast, some Asian countries, such as Japan and South Korea, offer classifications like “quasi-drugs” or “functional cosmetics,” which allow limited therapeutic claims with moderate regulatory oversight [9,10].

Scientifically, cosmeceuticals rely on the pharmacological activity of their ingredients. Notable actives include retinoids, peptides, α/β-hydroxy acids (AHAs/BHAs), antioxidants (such as vitamin C and coenzyme Q10), and botanical extracts like green tea polyphenols and bakuchiol [11,12,13,14]. These compounds have demonstrated potential in stimulating collagen synthesis, inhibiting matrix metalloproteinases (MMPs), neutralizing reactive oxygen species (ROS), and enhancing skin renewal. However, variability in formulation, ingredient stability, and cutaneous bioavailability can limit their efficacy in real-world settings [15,16].

The objectives of this review are threefold:

• To summarize the current landscape of anti-aging cosmeceuticals, focusing on mechanisms of action;
• To critically assess the clinical and preclinical evidence supporting their efficacy; and
• To examine the regulatory frameworks and consumer trends that influence their development and market adoption.

This review synthesizes findings from the last decade, with particular focus on literature published since 2020. By integrating recent advances, regulatory updates, and clinical data, the paper aims to support formulators, dermatologists, and regulatory professionals in understanding the complex, evolving nature of anti-aging cosmeceuticals.

2. Materials and Methods

This review was conducted using a structured and systematic approach to identify, evaluate, and synthesize relevant literature pertaining to cosmeceuticals and anti-aging mechanisms, clinical efficacy, and regulatory frameworks.

2.1. Literature Search Strategy

A comprehensive search of scientific literature was performed across multiple databases including PubMed, Scopus, Web of Science, and Google Scholar. The search included peer-reviewed articles published up to July 2025, with a specific emphasis on research conducted within the past five years (2020–2025) to ensure the review reflects the most current evidence.

The following keywords and Boolean operators were used:

“cosmeceuticals” AND “anti-aging” OR “skin aging” OR “wrinkles” OR “collagen synthesis” OR “retinoids” OR “peptides” OR “antioxidants” OR “botanicals” OR “regulation of cosmetics” OR “skin microbiome” OR “topical delivery systems”.

Filters were applied to select original research articles, randomized controlled trials, clinical studies, in vitro and in vivo studies, and systematic reviews or meta-analyses. Editorials, opinion pieces, and non-peer-reviewed sources were excluded unless otherwise stated.

2.2. Inclusion and Exclusion Criteria

Studies were included if they met the following criteria:

• Published in English;
• Described the mechanism of action, clinical evaluation, or formulation science of anti-aging cosmeceuticals;
• Provided data on efficacy, safety, or regulatory context.

Studies were excluded if they

• Did not address anti-aging or cosmeceutical applications;
• Were not supported by experimental or clinical data;
• Lacked adequate methodological transparency or were duplicated across sources.

2.3. Data Extraction and Synthesis

Key data extracted from the selected articles included

• Study design and sample size;
• Type of active ingredient(s);
• Biological mechanism and target;
• Measured endpoints (e.g., wrinkle depth, skin hydration, elasticity);
• Formulation type and delivery system;
• Reported efficacy and safety outcomes;
• Regulatory classifications and market claims.

All included articles were critically assessed for scientific rigor and relevance to the scope of the review. Data were synthesized narratively under thematic categories such as ingredient class, mechanism of action, formulation technology, and regulatory perspective.

2.4. Compliance and Ethics

As this study is a review of previously published literature, no new human or animal subjects were involved, and no ethical approval was required. No unpublished datasets were analyzed.

3. Results

3.1. Key Concepts and Definitions

Cosmeceuticals are defined as topically applied products containing biologically active ingredients that have therapeutic effects on the skin, beyond mere cosmetic enhancement [17,18]. The term, while widely used in commercial and academic contexts, lacks a standardized definition across regulatory agencies. In the USA, for example, the FDA does not recognize “cosmeceutical” as a regulatory classification, requiring products to be labeled as either cosmetics (intended for beautification) or drugs (intended to treat or prevent disease) [7].

The anti-aging segment refers to products and ingredients that aim to reduce, delay, or prevent visible signs of skin aging, such as wrinkles, loss of elasticity, hyperpigmentation, and rough texture [19]. Aging is understood to be driven by both intrinsic (genetic, chronological) and extrinsic (UV radiation, pollution, lifestyle) factors [20,21]. Effective anti-aging cosmeceuticals typically target the biochemical processes underlying these changes, such as oxidative stress, collagen degradation, and epidermal thinning [22,23]. In addition to the well-established intrinsic and extrinsic factors of skin aging, endocrine signaling plays a critical role in regulating dermal structure, barrier function, pigmentation, and sebaceous activity. Several hormones influence cutaneous aging through specific intracellular pathways that modulate collagen synthesis, fibroblast activity, oxidative defense, and inflammation [10].

Table 1. Summary of main hormones, their cutaneous effects and key pathways.

Hormone (References)	Cutaneous Effects	Key Pathways
Estrogens [25]	Increases collagen and elastin synthesis, improves hydration, reduces wrinkles	PI3K/AKT, MAPK/ERK, Wnt/β-catenin
Androgens [26]	Stimulates sebum production, regulates hair cycle, contributes to acne and alopecia	AR-mediated transcription, TGF-β
Insulin/IGF-1 [27,28]	Enhances proliferation of keratinocytes and fibroblasts; implicated in acne	PI3K/AKT/mTOR, MAPK/ERK, FoxO1
Melatonin [24]	Antioxidant, anti-inflammatory, stimulates skin regeneration, UV protective	PI3K/AKT, MAPK, Wnt/β-catenin, NF-κB

and Figure 1 schematically illustrate the key intracellular signaling cascades activated by melatonin, estrogens, androgens, and insulin-like growth factor-1 (IGF-1), highlighting their dermatologic effects.

Figure 1. Intracellular pathways activated by melatonin, estrogens, androgens, and IGF-1 and their dermatologic effects. Melatonin and estrogen through membrane receptor (mER) promotes antioxidant defense and regeneration via PI3K/AKT, MAPK/ERK and Wnt/β-catenin [24]. Estrogens act also through nuclear (ERα/ERβ) receptors, enhancing collagen synthesis, photoprotection, and anti-inflammatory responses [25]. Androgens stimulate sebum production and hair cycling through AR-mediated gene transcription and TGF-β modulation [26]. IGF-1 promotes proliferation and wound healing via PI3K/AKT/mTOR and MAPK/ERK signaling. The inhibition of FoxO1 plays a significant role in skin physiology, particularly in sebaceous gland activity and acne pathogenesis [27,28].

Figure 1. Intracellular pathways activated by melatonin, estrogens, androgens, and IGF-1 and their dermatologic effects. Melatonin and estrogen through membrane receptor (mER) promotes antioxidant defense and regeneration via PI3K/AKT, MAPK/ERK and Wnt/β-catenin [24]. Estrogens act also through nuclear (ERα/ERβ) receptors, enhancing collagen synthesis, photoprotection, and anti-inflammatory responses [25]. Androgens stimulate sebum production and hair cycling through AR-mediated gene transcription and TGF-β modulation [26]. IGF-1 promotes proliferation and wound healing via PI3K/AKT/mTOR and MAPK/ERK signaling. The inhibition of FoxO1 plays a significant role in skin physiology, particularly in sebaceous gland activity and acne pathogenesis [27,28].

• Melatonin, via membrane-bound MT1/MT2 receptors, activates PI3K/AKT/mTOR, MAPK/ERK, and Wnt/β-catenin pathways, leading to dermal fibroblast proliferation, increased collagen and elastin synthesis, stimulation of cutaneous stem cells, and robust antioxidant protection [24].
• Estrogens exert effects both through membrane estrogen receptors (mER) and nuclear receptors (ERα/ERβ). The membrane route promotes fibroblast proliferation and extracellular matrix (ECM)
• Synthesis via PI3K/AKT and MAPK/ERK signaling, while nuclear receptor activation drives TGF-β–mediated gene transcription, enhancing photoprotection and anti-inflammatory responses [25].
• Androgens act through androgen receptors (AR), regulating the hair follicle cycle, increasing sebum production, and modulating TGF-β signaling [26].
• IGF-1 binds to its receptor (IGFR), stimulating keratinocyte and fibroblast proliferation through PI3K/AKT/mTOR and MAPK/ERK pathways. Inhibition of FoxO1 under IGF-1 influence is particularly relevant in the pathogenesis of hormone-related acne [27,28].

Several commonly used ingredient classes are central to the anti-aging cosmeceutical field (Table 2):

• Retinoids: Stimulate collagen synthesis and epidermal turnover [12];
• Peptides: Signal fibroblast activity and matrix repair [29];
• Antioxidants: Neutralize free radicals and reduce oxidative damage [11];
• Botanical extracts: Offer multi-targeted effects with lower irritancy profiles [14].

Table 2. Mechanisms of action of key anti-aging cosmeceutical ingredients.

Ingredient Class (References)	Example Actives	Primary Mechanisms of Action	Key Clinical Evidence
Retinoids [4,12,30,31]	Retinol, Retinoic Acid, Retinyl Retinoate, Hydroxypinacolone Retinoate	Stimulate collagen synthesis, normalize keratinocyte differentiation, upregulate extracellular matrix genes via RAR activation	0.3% retinol improved wrinkle depth/texture in 12 weeks with less erythema than tretinoin; next-gen retinoids (retinyl retinoate, HPR) show improved tolerability but limited long-term data
Peptides–Signal [29,32,33]	Palmitoyl pentapeptide-4 (Matrixyl)	Stimulate fibroblast activity, enhance collagen & glycosaminoglycan synthesis	RCTs: improved elasticity and reduced fine lines in 4–8 weeks
Peptides–Neurotransmission-Inhibiting [29,32]	Acetyl hexapeptide-3 (Argireline)	Inhibit SNARE complex, reduce dynamic wrinkles (botulinum-like effect)	Periorbital wrinkle reduction in 8 weeks; less potent than Botox but safer
Peptides–Carrier [33,34]	Copper tripeptide-1	Deliver trace elements for enzymatic repair, antioxidant defense, extracellular matrix stabilization	In vivo: improved elasticity, pigmentation, and wound healing; liposomal delivery enhances penetration
Antioxidants [34,35,36,37,38]	Vitamin C, CoQ10	Neutralize reactive oxygen species, photoprotection, mitochondrial support, anti-inflammatory	Vitamin C + E + ferulic acid doubled UV photoprotection; topical CoQ10 improved smoothness, mitochondrial function
α-/β-Hydroxy Acids [34,38]	Glycolic acid, Salicylic acid	Promote exfoliation, epidermal renewal, stimulate collagen via controlled wounding	10% glycolic acid for 12 weeks improved fine lines and lentigines; encapsulated delivery improves tolerability
Botanical Extracts/Polyphenols [39,40,41,42]	Bakuchiol, Epigallocatechin gallate, Resveratrol, Curcumin	Antioxidant, anti-inflammatory, inhibit matrix metalloproteinases, stimulate collagen, photoprotection	Bakuchiol comparable to retinol over 12 weeks with less irritation; Epigallocatechin gallate nanoparticles enhanced stability/anti-photoaging; Oral microencapsulated curcumin improved wrinkles & pigmentation in 42 days; Resveratrol improved elasticity/density

Table 2. Mechanisms of action of key anti-aging cosmeceutical ingredients.

Ingredient Class (References)	Example Actives	Primary Mechanisms of Action	Key Clinical Evidence
Retinoids [4,12,30,31]	Retinol, Retinoic Acid, Retinyl Retinoate, Hydroxypinacolone Retinoate	Stimulate collagen synthesis, normalize keratinocyte differentiation, upregulate extracellular matrix genes via RAR activation	0.3% retinol improved wrinkle depth/texture in 12 weeks with less erythema than tretinoin; next-gen retinoids (retinyl retinoate, HPR) show improved tolerability but limited long-term data
Peptides–Signal [29,32,33]	Palmitoyl pentapeptide-4 (Matrixyl)	Stimulate fibroblast activity, enhance collagen & glycosaminoglycan synthesis	RCTs: improved elasticity and reduced fine lines in 4–8 weeks
Peptides–Neurotransmission-Inhibiting [29,32]	Acetyl hexapeptide-3 (Argireline)	Inhibit SNARE complex, reduce dynamic wrinkles (botulinum-like effect)	Periorbital wrinkle reduction in 8 weeks; less potent than Botox but safer
Peptides–Carrier [33,34]	Copper tripeptide-1	Deliver trace elements for enzymatic repair, antioxidant defense, extracellular matrix stabilization	In vivo: improved elasticity, pigmentation, and wound healing; liposomal delivery enhances penetration
Antioxidants [34,35,36,37,38]	Vitamin C, CoQ10	Neutralize reactive oxygen species, photoprotection, mitochondrial support, anti-inflammatory	Vitamin C + E + ferulic acid doubled UV photoprotection; topical CoQ10 improved smoothness, mitochondrial function
α-/β-Hydroxy Acids [34,38]	Glycolic acid, Salicylic acid	Promote exfoliation, epidermal renewal, stimulate collagen via controlled wounding	10% glycolic acid for 12 weeks improved fine lines and lentigines; encapsulated delivery improves tolerability
Botanical Extracts/Polyphenols [39,40,41,42]	Bakuchiol, Epigallocatechin gallate, Resveratrol, Curcumin	Antioxidant, anti-inflammatory, inhibit matrix metalloproteinases, stimulate collagen, photoprotection	Bakuchiol comparable to retinol over 12 weeks with less irritation; Epigallocatechin gallate nanoparticles enhanced stability/anti-photoaging; Oral microencapsulated curcumin improved wrinkles & pigmentation in 42 days; Resveratrol improved elasticity/density

Another emerging term is “functional cosmetics”, especially in Asian markets, describing products that combine beauty with health benefits [9]. This reflects a growing trend toward “skin health” rather than “cosmetic correction”.

In this review, the term cosmeceutical will refer to any cosmetic product with active ingredients that provide clinically or mechanistically substantiated anti-aging effects.

3.2. Recent Advances in Anti-Aging Cosmeceuticals

3.2.1. Retinoids and Retinol Derivatives

Retinoids remain the gold standard in topical anti-aging interventions due to their well-documented ability to stimulate dermal collagen synthesis, normalize keratinocyte differentiation, and reduce the appearance of fine lines and wrinkles [12,43]. Retinoic acid (RA) is the most biologically active form, binding directly to nuclear retinoic acid receptors (RARs) to regulate gene transcription involved in ECM remodeling. However, the potent clinical efficacy of RA is often offset by adverse effects such as erythema, dryness, and peeling, prompting cosmetic formulations to rely on precursors—including retinol, retinaldehyde, and retinyl esters—which must undergo enzymatic conversion within the skin [44].

Recent formulation innovations have focused on encapsulation strategies—such as lipid nanoparticles, polymeric nanocarriers, and cyclodextrin complexes—to enhance retinoid stability, control release, and improve penetration through the stratum corneum [45]. These systems protect retinoids from oxidative degradation and reduce irritancy by allowing more gradual delivery to target sites in the epidermis and dermis.

Clinically, the benefits of optimized delivery have been confirmed. In a 2021 randomized controlled trial, topical 0.3% retinol applied for 12 weeks produced statistically significant reductions in wrinkle depth and improved skin texture, while inducing less erythema compared to tretinoin, reinforcing the role of retinol as a well-tolerated yet effective alternative to prescription RA [46]. Emerging research has also begun to evaluate next-generation retinoids, including retinyl retinoate and hydroxypinacolone retinoate (HPR, also marketed as granactive retinoid), which are designed to improve photostability and reduce irritation potential compared with conventional retinol [47]. For example, in a pooled analysis of six vehicle-controlled studies, Farris et al. investigated a 0.1% stabilized bioactive retinol formulation in patients with photoaged skin (n > 300). Significant improvements were observed in wrinkles, uneven pigmentation, and skin roughness as early as week 4, with benefits sustained through 12 weeks; adverse effects were predominantly mild, suggesting favorable tolerability [30].

Beyond stabilized retinol, new supramolecular approaches are being tested. Bai et al. developed nanoparticles co-encapsulating retinyl propionate (RP) and HPR, which demonstrated enhanced stability, sustained release, and deeper penetration in vitro. In a clinical setting, the formulation reduced periorbital wrinkle depth while causing minimal irritation, highlighting its potential as a low-irritancy anti-wrinkle strategy [47].

Clinical head-to-head comparisons are also emerging. In a double-blind trial [48], a topical serum containing 0.1% HPR plus peptides was compared against a single session of fractional CO₂ laser in women aged 40–65 with moderate photodamage (n = 34). After 16 weeks, the HPR-peptide serum achieved equal or superior improvements in wrinkles, hyperpigmentation, and skin texture compared with laser treatment, with fewer adverse effects—underscoring the promise of next-generation topical retinoids [48].

Synergistic effects have also been reported when retinoids are combined. Wang et al. demonstrated that combining RP and HPR at optimized ratios improved fibroblast proliferation and upregulated anti-aging gene expression in vitro; in vivo, an 8-week clinical study showed improvements in skin elasticity and wrinkle severity, again with minimal irritation [49]. More recently, Fang et al. tested a functional formulation of RP + HPR + vitamin C in 120 Chinese women. After 12 weeks, participants exhibited significant improvements in both anti-aging (wrinkle reduction, skin elasticity) and whitening outcomes (reduced pigmentation), highlighting the potential for combination formulations to enhance efficacy [31].

3.2.2. Antioxidants: Vitamin C, Coenzyme Q10

Oxidative stress is recognized as a central driver of both intrinsic and extrinsic skin aging, promoting collagen degradation through MMP activation and accelerating the accumulation of oxidized proteins, lipids, and DNA lesions [20]. Antioxidants, therefore, represent a cornerstone of anti-aging cosmeceutical strategies.

Ascorbic acid (vitamin C) is among the most studied antioxidants in dermatology. It functions as a cofactor for prolyl and lysyl hydroxylases in collagen synthesis, directly scavenges ROS [50], and regenerates oxidized vitamin E [11]. However, its instability in aqueous formulations and limited skin penetration have historically constrained its effectiveness. A landmark randomized, controlled trial involving 20 healthy volunteers evaluated a topical formulation containing vitamins C and E plus ferulic acid. The inclusion of ferulic acid significantly improved photoprotection against UV-induced erythema, nearly doubling efficacy compared to vitamins C + E alone [51]. More recently, a 5% ascorbic acid cream applied daily for 6 months significantly reduced deep wrinkles and improved texture, while a 10% formulation used for 12 weeks markedly attenuated photoaging compared to placebo [36]. Adjunctive delivery methods such as sonophoresis and microneedle mesotherapy further improved elasticity, barrier function, and pigmentation outcomes in clinical use [36]. A multidisciplinary consensus highlights vitamin C’s role in replenishing antioxidants, inhibiting melanogenesis, and supporting collagen integrity, while underscoring the need for stable and permeable formulations [52]

Coenzyme Q10 (ubiquinoneis an endogenous antioxidant integral to mitochondrial energy metabolism. In a controlled study with 73 female participants (20–66 years), topical application of a CoQ10-containing formula increased epidermal CoQ10 levels and mitochondrial energy metabolism markers, alongside subjective improvements in skin smoothness [35]. A recent review highlighted clinical improvements in skin roughness and wrinkle depth after 4–12 weeks of topical CoQ10 formulations, though most trials were small (<50 participants) and industry-sponsored [37]. Clinical reviews further report reductions in wrinkle depth, neck creases, and improvements in elasticity after 2–4 weeks of CoQ10 use [53]. To overcome poor dermal penetration, advanced delivery platforms such as protransfersomal emulgels have been tested in UV-induced aging models, increasing fibroblast density and collagen content without irritation [54]. Complementary lipid-nanoparticle formulations are also being developed to enhance skin delivery and stability [55,56,57].

3.3. Peptides: Signal Modulators for Skin Repair

Peptides represent a rapidly growing and scientifically diverse class of cosmeceutical actives due to their ability to regulate cell signaling pathways and stimulate ECM remodeling [58]. These bioactive short chains of amino acids can mimic endogenous skin messengers such as growth factors, cytokines, or ECM fragments that are naturally involved in collagen production, wound healing, and intercellular communication [59].

Among the most extensively studied are signal peptides, particularly palmitoyl pentapeptides (e.g., Matrixyl or palmitoyl pentapeptide-4). These molecules enhance dermal fibroblast activity, leading to increased synthesis of collagen I, III, and IV as well as glycosaminoglycans, thereby improving skin firmness, elasticity, and hydration. Clinical evidence shows that topical application over 4–8 weeks can reduce wrinkle depth and improve surface smoothness [60,61,62].

Another important subgroup includes neurotransmitter-inhibiting peptides, such as acetyl hexapeptide-3 (Argireline), which are designed to reduce dynamic wrinkles caused by repetitive facial muscle contraction. These peptides function by inhibiting SNARE complex formation at the neuromuscular junction, partially mimicking the wrinkle-smoothing effects of botulinum toxin but without the need for injections [60,63]. While less potent than botulinum toxin, their non-invasive nature and favorable safety profile make them attractive for daily skincare use.

Recent developments have also introduced carrier peptides, with copper tripeptide-1 (GHK–Cu) being the most extensively studied representative. These peptides act as shuttles for trace elements such as copper, facilitating their transport into the skin where they serve as essential cofactors for enzymatic processes involved in wound repair, antioxidant defense, and ECM stabilization. Evidence from both in vitro and in vivo studies demonstrates that GHK–Cu stimulates collagen, elastin, and glycosaminoglycan synthesis, accelerates wound healing, and exerts antioxidant activity by enhancing enzymes such as superoxide dismutase [33,64]. Clinical investigations, although generally of modest scale and short duration, report improvements in wrinkle depth, skin elasticity, and pigmentation following topical application, underscoring the peptide’s multifunctional role in dermal rejuvenation [32]. Delivery strategies are also evolving: encapsulation of GHK–Cu in liposomal carriers (~100 nm) has been shown to improve peptide stability, enhance penetration, and significantly inhibit elastase activity in vitro, thereby reducing ECM degradation [34]. Despite these promising findings, limitations remain, including variability in study designs, relatively small participant cohorts, and a lack of long-term head-to-head comparisons against established anti-aging actives. Nevertheless, carrier peptides such as GHK–Cu expand the cosmeceutical anti-aging portfolio beyond structural support, offering multifunctional benefits that integrate tissue repair, ECM remodeling, and oxidative protection.

A major limitation across all peptide types remains stability and penetration. Many peptides are hydrophilic and prone to enzymatic degradation in the skin’s upper layers. To address these issues, formulators are increasingly turning to lipid-based encapsulation, peptide-coupled liposomes, and nanocarrier systems to protect the active molecule, prolong release, and improve dermal bioavailability [65].

3.4. α-Hydroxy Acids and β-Hydroxy Acids: Exfoliation and Renewal

AHAs and BHAs are chemical exfoliants widely used in anti-aging skincare for their ability to promote epidermal turnover, refine surface texture, and reduce pigmentation irregularities [66]. AHAs include glycolic acid, lactic acid, and citric acid, while the most common BHA is salicylic acid.

Glycolic acid, derived from sugarcane, is the smallest and most potent AHA, enabling efficient penetration into the epidermis. It weakens the corneodesmosomal bonds between corneocytes in the stratum corneum, facilitating controlled desquamation and stimulating epidermal renewal [67]. Beyond its surface effects, glycolic acid also promotes dermal remodeling by upregulating collagen and hyaluronic acid synthesis in fibroblasts, contributing to improved firmness and hydration [38].

Clinical evidence supports its efficacy: in a double-blind trial, 10% glycolic acid applied for 12 weeks significantly improved photodamaged skin, reducing roughness, lentigines, and fine lines [68]. Salicylic acid, due to its lipophilicity, penetrates into the pores and exerts both keratolytic and comedolytic effects, making it well-suited for oily or acne-prone aging skin [69].

However, the benefits of AHAs must be balanced with their irritation potential. AHAs promote exfoliation by thinning the stratum corneum, which disrupts the skin’s natural barrier and exposes underlying, more vulnerable layers to UV radiation—leading to increased erythema, stinging sensations, and heightened sun sensitivity [38,70]. Clinically, even short-term (4-week) daily use of 10% glycolic acid at pH 3.5 was shown in a randomized, double-blind study (n = 29) to increase sensitivity to UV exposure, evidenced by greater sunburn cell formation and lowered minimal erythemal dose (MED)—effects which reversed after one week of discontinuation [71].

For optimal tolerability, cosmeceutical formulations require careful pH adjustment (typically between 3.5 and 4.0 for daily use products) and concurrent photoprotection to prevent UV-induced damage during use [72]. Recent advances in delivery systems aim to balance efficacy with reduced irritation by modulating release kinetics and improving dermal targeting. For example, a study utilizing a pullulan–collagen electrospun nanofiber mask loaded with AHAs and BHAs demonstrated favorable structural integrity, biocompatibility, and gradual release in vitro, with significantly higher fibroblast and stem cell viability compared to conventional formulations—although no human trial data were yet reported [34]. Similarly, a protein-based sustained-release matrix (SVX:GA) has been evaluated in both in vitro assays and small human studies, where topical application of SVX-encapsulated glycolic acid reduced erythema compared to unencapsulated glycolic acid at the same concentration, highlighting improved tolerability without loss of efficacy; however, sample sizes were modest (<40 participants) and follow-up was short-term (≤4 weeks) [73]. Broader polymeric platforms, such as hydrogels, microspheres, and nanoparticles, have also been reviewed for their ability to provide controlled release of hydroxy acids, improve chemical stability, and enhance penetration through the stratum corneum [74].

3.5. Botanical Extracts: Multifunctional and Natural Alternatives

Plant-derived actives are increasingly favored in cosmeceutical formulations due to their antioxidant, anti-inflammatory, and skin-calming properties. Many botanical extracts also modulate signaling pathways relevant to aging, such as nuclear factor erythroid 2-related factor 2 (Nrf2) activation and MMPs inhibition [75].

Bakuchiol, a meroterpene phenol derived from Psoralea corylifolia, is one of the most prominent botanical alternatives to retinol. It exhibits similar anti-aging effects, such as stimulating collagen synthesis and reducing hyperpigmentation, but with significantly lower irritation potential [14]. In a 2019 randomized, double-blind, 12-week study (n = 44), topical bakuchiol 0.5% cream demonstrated efficacy comparable to retinol 0.5% in reducing wrinkle severity and pigmentation yet was significantly better tolerated [39]. Recent preclinical work further established bakuchiol’s multidirectional anti-aging action, including antioxidative and anti-inflammatory effects, enhanced ECM protein expression, and accelerated epidermal regeneration and wound healing [76]. Innovative formulations have also emerged: a split-face, double-blind clinical study comparing 0.5% bakuchiol oil cream to encapsulated 0.5% bakuchiol cream (28 days, n = 17) revealed that encapsulated formulations significantly outperformed oil-based ones—boosting hydration by up to ~11%, reducing pore visibility by ~33%, sebum production by ~41%, and wrinkle appearance by ~76% [77]. Mechanistically, a 2025 study in C. elegans demonstrated that bakuchiol extended lifespan via activation of DAF-16 and enhanced oxidative stress tolerance through upregulation of sod-3 expression, underscoring its potential as a longevity-promoting agent [78]. Systematic review of human clinical trials confirms growing interest in bakuchiol for aging, acne, and post-inflammatory hyperpigmentation, yet highlights a need for rigorously designed, controlled studies [79]. Lastly, an ongoing clinical trial evaluating bakuchiol’s efficacy in treating post-inflammatory hyperpigmentation is poised to further elucidate its therapeutic potential [80].

Green tea polyphenols, particularly epigallocatechin gallate (EGCG), have been extensively investigated for their capacity to attenuate oxidative stress, suppress pro-inflammatory cytokine production, and inhibit MMPs, thereby reducing collagen degradation [81]. In a randomized, double-blind, placebo-controlled trial involving 56 women aged 40–65 years, daily oral supplementation with green tea catechins (~1400 mg/day for 12 weeks) significantly improved skin elasticity and hydration, with histological analysis confirming reduced solar elastosis [82]. However, limitations of this study include oral rather than topical administration, modest sample size, and a predominantly female, light-skinned cohort. More recent research has focused on enhancing EGCG bioavailability through advanced delivery systems. For example, EGCG encapsulated in mesoporous silica nanoparticles conjugated with nonapeptide-1 demonstrated improved stability, skin penetration, and anti-photoaging efficacy in preclinical models, emphasizing the translational promise of such engineered formulations [40].

Resveratrol, a stilbene polyphenol present in grape skins and red wine, exerts potent antioxidant effects and activates sirtuin-1 (SIRT1) signaling pathways associated with cellular longevity and stress resilience [83].

Clinical studies suggest topical benefits: in an 8-week trial, a nighttime antioxidant blend of resveratrol (1%), baicalin (0.5%), and vitamin E (1%) improved multiple skin aging parameters, including an average 18.9% increase in periorbital dermal thickness, as assessed by ultrasound [41]. More recent preclinical findings underscore resveratrol’s role in photoaging and pigmentation control, with a 63% reduction in melanosome content observed in fibroblasts [42] and visible lightening of UVB-induced pigmentation in dark-skinned Yucatan swine following 1% topical application [84]. Reviews further highlight resveratrol’s dermatological promise—spanning anti-aging, photoprotection, anti-inflammatory, and wound-healing applications—while noting ongoing challenges with bioavailability and photoinstability that drive interest in nanocarrier delivery strategies [85]. Importantly, a clinical trial is registered to investigate the efficacy of a resveratrol-based formulation for enhancing skin quality and modulating inflammatory cytokines, underscoring its translational potential [86].

Curcumin, the principal polyphenol of Curcuma longa, has emerged as a promising cosmeceutical ingredient due to its potent antioxidant, anti-inflammatory, and photoprotective properties. Recent reviews highlight its ability to attenuate UV-induced oxidative stress, downregulate matrix metalloproteinases, and modulate signaling pathways relevant to skin aging, while also underscoring the challenges of poor solubility and stability that limit topical bioavailability [87]. Advances in formulation science—including liposomes, solid lipid nanoparticles, and nanoemulsions—have demonstrated enhanced stability, penetration, and efficacy of curcumin in dermal applications [88]. More recently, mechanistic studies confirm curcumin’s potential as an anti-photoaging agent, with evidence for improved elasticity, reduced wrinkle formation, and suppression of pro-inflammatory mediators [89].

Despite their benefits, botanical extracts present unique formulation challenges. Variability in active compound content due to differences in plant species, cultivation conditions, and extraction methods can lead to inconsistent product performance. Additionally, some botanical actives are chemically unstable or prone to oxidation, which can reduce efficacy over time. Potential allergenicity from plant-derived proteins or residual solvents must also be addressed. For these reasons, rigorous standardization protocols, controlled extraction processes, and stability-optimizing delivery systems are essential to ensure reproducible efficacy and safety [90].

4. Regulatory, Safety, and Consumer Trends

4.1. Regulatory Frameworks

The classification and regulation of cosmeceuticals remain inconsistent across global jurisdictions, creating substantial challenges for product development, claim substantiation, labeling, and international marketing. This lack of harmonization often forces manufacturers to adapt formulations and promotional materials to each target market, thereby increasing both cost and complexity.

In the United States, the Food and Drug Administration (FDA) does not formally recognize the term cosmeceutical. Products must be classified either as cosmetics—intended to cleanse, beautify, or alter appearance—or as drugs, intended to diagnose, treat, prevent, or otherwise affect body structure or function [91]. This distinction is critical because therapeutic claims, such as “stimulates collagen production” or “improves skin barrier function,” place a product in the drug category, requiring extensive pre-market approval, including safety and efficacy trials [92]. Consequently, U.S. manufacturers often rely on carefully worded claims that imply, but do not explicitly state, physiological effects.

In the European Union, cosmetics are regulated under Regulation (EC) No 1223/2009, which emphasizes product safety, accurate labeling, and consumer protection [93]. Anti-aging products may highlight functional benefits, but claims suggesting structural or functional skin modification are prohibited unless supported by robust scientific evidence. Commission Regulation (EU) No 655/2013 specifies criteria for claim substantiation, including truthfulness, evidential support, and fairness [94]. Manufacturers must maintain product information files documenting safety assessments, stability data, and validation studies.

Asian markets such as Japan and South Korea adopt more flexible classifications, including “quasi-drugs” and “functional cosmetics.” These categories allow limited therapeutic claims—for example, “reduces wrinkles” or “improves skin elasticity”—without requiring full pharmaceutical-level regulation. South Korea’s Ministry of Food and Drug Safety, for instance, mandates that such claims be supported by clinical trial data or validated mechanistic evidence [95]. This regulatory flexibility has stimulated innovation, positioning these countries as leaders in advanced cosmeceutical development.

The rising demand for natural and botanical cosmeceuticals has introduced further regulatory complexity. Authorities are increasingly focused on ingredient standardization, batch-to-batch consistency, allergen labeling, and verification of sustainability claims [96].

4.2. Safety Assessment and Testing

Safety evaluation of cosmeceuticals encompasses dermal toxicity, allergenicity, phototoxicity, and long-term exposure risks. Historically, in vivo animal testing was the primary method. However, ethical concerns and restrictions—such as the European Union’s ban on animal testing under Regulation (EC) 1223/2009—have shifted the field toward validated in vitro and in silico alternatives [93].

Current strategies combine multiple methodologies. Patch testing remains a widely used method to assess irritation and sensitization in human volunteers. Advanced laboratory systems, such as three-dimensional reconstructed human epidermis models, allow cytotoxicity and barrier function assessment without animal testing. Computational tools, including quantitative structure–activity relationship (QSAR) models, are increasingly applied to predict bioactivity and toxicity of novel compounds before formulation [97].

In addition to toxicity testing, stability assessments ensure that active ingredients maintain efficacy and safety throughout shelf life. These evaluations include monitoring pH, viscosity, and physical appearance, alongside microbial limit testing according to pharmacopeial standards such as USP <51> [98,99]. Photostability and packaging compatibility studies are particularly important for light-sensitive actives like retinoids and vitamin C.

Post-market safety surveillance is also gaining importance. Cosmetovigilance systems, analogous to pharmacovigilance for drugs, collect and analyze consumer-reported adverse reactions to identify potential risks and guide formulation or labeling adjustments [100,101].

Consumer behavior strongly influences safety expectations. Millennials and Generation Z, in particular, prioritize dermatologist-tested, clinically validated, and eco-conscious products. They frequently scrutinize ingredient lists, and certifications from third-party organizations, as well as the availability of clinical trial data on product websites, serve as critical trust signals [102,103].

Digital platforms further amplify these dynamics. Social media influencers, dermatologists, and skincare enthusiasts on platforms such as Instagram, TikTok, and YouTube actively review products, dissect formulations, and discuss safety concerns. This rapid dissemination of information accelerates both consumer adoption and rejection. Studies confirm that influencers and online communities significantly shape trust and purchase intent, particularly through credibility, authenticity, and engagement [102,104].

5. Future Perspectives and Challenges

Despite the remarkable growth of cosmeceuticals in the anti-aging domain, several scientific, regulatory, and ethical hurdles must be addressed to ensure sustainable innovation, maintain consumer trust, and deliver measurable results.

5.1. Personalized and Precision Cosmeceuticals

Advances in skin microbiome research, genomics, and artificial intelligence (AI) are driving the development of personalized cosmeceuticals, moving beyond one-size-fits-all products toward tailored formulations that account for an individual’s unique skin biology, environment, and lifestyle [105,106]. Genomic profiling and microbiome mapping can reveal predispositions to conditions such as hyperpigmentation, premature aging, or barrier dysfunction, enabling the selection of actives that specifically target these vulnerabilities [107].

AI-powered diagnostic tools—delivered through smartphone applications, connected devices, or in-clinic imaging—can now evaluate wrinkle depth, pigmentation patterns, hydration levels, and pore size in real time. These tools recommend customized product regimens and monitor progress over time. While they offer unprecedented potential for personalization, their introduction into the consumer market raises critical issues related to regulatory oversight, scientific validation of recommendations, and protection of sensitive biometric data [108].

5.2. Regulatory Harmonization and Global Claims Standards

A major challenge for the global cosmeceutical industry is the absence of a unified regulatory framework. Definitions, permissible claims, and testing requirements differ significantly across regions, creating barriers to international trade and complicating multinational product launches. Establishing internationally recognized guidelines—similar to the International Council for Harmonisation (ICH) model in pharmaceuticals—could streamline product development, ensure safety, and reduce redundancy in compliance processes [109,110,111].

Equally important is the establishment of standardized efficacy claims and testing protocols. Clear benchmarks for clinical substantiation would distinguish products with robust scientific validation from those driven primarily by marketing claims, thereby strengthening consumer trust and promoting industry accountability [105]. Standardization could also mitigate the risk of misleading claims, which undermine confidence in the field as a whole.

5.3. Natural Actives and Sustainability

The growing demand for natural and biodegradable ingredients has raised concerns about over-harvesting, supply chain transparency, and ecotoxicity. As the industry shifts toward green chemistry and circular beauty, biotechnology-based solutions—such as lab-grown collagen, algae extracts, and engineered plant cells—are gaining momentum [112].

At the same time, formulators must address inherent challenges associated with natural actives, including chemical instability, batch-to-batch variability, and allergenic potential, to ensure consistent performance and safety [113].

6. Discussion

The cosmeceutical market, particularly in anti-aging, is expanding rapidly at the convergence of scientific innovation, consumer demand, and commercial opportunity. As reviewed in previous sections, a wide array of bioactive compounds—including retinoids, peptides, antioxidants, and botanical extracts—have demonstrated clinically measurable improvements in skin aging parameters such as wrinkle depth, hydration, pigmentation uniformity, and elasticity [4,17,50,114].

Despite these advances, translating promising in vitro results into consistent in vivo outcomes remains a major challenge. One key limitation lies in percutaneous absorption: many actives, particularly hydrophilic peptides and large polyphenols, encounter significant difficulty penetrating the stratum corneum barrier [115,116]. Recent innovations—such as lipid nanoparticle encapsulation, polymeric carriers, and microneedle delivery systems—are showing potential to overcome these barriers by enhancing dermal penetration, protecting active stability, and enabling controlled release [117,118,119].

The quality and consistency of clinical evidence supporting cosmeceutical efficacy vary considerably across active classes. Next-generation retinoids such as hydroxypinacolone retinoate and retinyl retinoate demonstrate encouraging tolerability and efficacy profiles; however, most available trials are short in duration (8–16 weeks), modest in sample size (<150 participants), and frequently industry-sponsored, with limited long-term or head-to-head data against established standards like tretinoin [30,31,47,48,49]. Bioactive peptides continue to attract interest for their multifunctional actions, including extracellular matrix repair, wrinkle modulation, and barrier reinforcement, but clinical trials remain small, with outcomes often restricted to surrogate biophysical measures rather than validated clinical endpoints [32,33]. Antioxidantssuch as vitamin C and coenzyme Q10 are supported by controlled human studies demonstrating improvements in photoprotection, dermal energy metabolism, and skin texture [35,37,51], though sample sizes are typically small and interventions short-term. Recent clinical advances include stable vitamin C formulations that reduce wrinkle depth and pigmentation over 12–24 weeks [36], and emerging CoQ10 delivery systems that enhance bioavailability and maintain stability [37]. Botanical polyphenols are emerging as innovative anti-aging agents. Nanoparticle-encapsulated EGCG enhances stability and anti-photoaging efficacy [40]. Oral microencapsulated curcumin significantly improved wrinkles, pigmentation, and skin luminosity in a 42-day nutricosmetic trial [90]. Resveratrol shows multifaceted benefits—clinical use with antioxidant blends improved photodamage [41], while new preclinical work demonstrated marked pigmentation control [42]. Despite challenges of bioavailability, advanced delivery systems and ongoing clinical trials [86] highlight their translational promise.

Bakuchiol, often described as a retinol alternative, has shown comparable efficacy to retinol in a 12-week randomized trial but with superior tolerability [39], and encapsulated formulations are emerging to optimize stability and penetration [77]. AHAs and BHAs remain well established for exfoliation and photoaging, though irritation continues to limit their use. Encapsulation and controlled-release formulations offer potential to improve tolerability, but current evidence is largely limited to preclinical models or short-term human studies [34,38].

Overall, robust evidence continues to support established actives such as retinoids, vitamin C, and AHAs, while newer actives—including bakuchiol, advanced peptides, and engineered botanical formulations—show translational promise. To fully define their role in daily dermatologic care, larger, long-term, independently conducted randomized controlled trials with standardized clinical endpoints are critically needed.

Regulatory ambiguity adds another layer of complexity. The absence of a harmonized global framework means that identical products may face entirely different classifications and claim restrictions across jurisdictions [110,120,121]. Products with pharmacological activity but insufficient oversight risk falling into a loosely regulated “quasi-medicinal” gray zone, raising safety and compliance concerns.

Market trends such as “clean,” “natural,” and “eco-friendly” labeling present both opportunities and pitfalls. These descriptors are often ill-defined and not supported by standardized scientific criteria [122]. While consumers frequently perceive natural ingredients as safer, several botanical extracts are known to be allergenic, photosensitizing, or unstable when improperly processed [110,123].

A particularly promising research direction involves microbiome-friendly formulations. Emerging studies suggest that some preservatives, surfactants, and harsh actives may disrupt skin microbial communities, potentially accelerating barrier decline and visible aging [124]. New formulations incorporating prebiotics, probiotics, and postbiotics aim to maintain or restore a healthy skin microbiota, with early clinical data indicating benefits for both barrier resilience and inflammation modulation [125,126].

Economic accessibility also remains an ethical consideration. Many advanced anti-aging cosmeceuticals are priced at a premium, limiting access for underserved populations, despite growing awareness of skin health equity [127,128]. Addressing this gap will require innovative pricing strategies, wider distribution models, and potentially, regulatory incentives for affordable formulations.

Finally, the integration of omics technologies (transcriptomics, proteomics, metabolomics) and AI-based diagnostics is reshaping the research and development landscape. Companies are increasingly leveraging big data analytics and machine learning to predict formulation performance, optimize ingredient combinations, and identify novel bioactives from natural and synthetic sources [129,130]. While these tools offer unprecedented opportunities for personalization and innovation, they must be coupled with rigorous validation, reproducibility standards, and robust data privacy safeguards [108,131].

In summary, the anti-aging cosmeceutical field is advancing rapidly, but it must overcome key scientific, regulatory, and ethical challenges to fulfill its full potential.

7. Conclusions

Anti-aging cosmeceuticals represent a dynamic and interdisciplinary domain at the intersection of dermatology, pharmacology, cosmetic science, and consumer behavior. This review has outlined the mechanisms of key bioactive ingredients—including retinoids, peptides, antioxidants, α-hydroxy acids, and botanicals—along with their formulation challenges, efficacy data, and regulatory status.

While many actives show promise in reducing signs of skin aging, standardized efficacy testing and globally harmonized regulations remain crucial for product credibility. The future of cosmeceuticals will likely involve greater personalization, integration of microbiome-friendly strategies, and increased reliance on AI and omics-driven innovation.

To realize the full therapeutic and commercial potential of anti-aging cosmeceuticals, future efforts must focus on clinical validation, regulatory reform, and sustainability. A balanced synergy between evidence-based formulation, ethical marketing, and consumer empowerment will define the next era of innovation in this rapidly evolving field.