The Role of Coenzyme Q10 in Skin Aging and Opportunities for Topical Intervention: A Review

J Clin Aesthet Dermatol. 2024;17(8):50–55.

by Edward (Ted) Lain, MD, MBA; Nick Agrawal, MS; Eduardo Ruvolo, MS; Julia M. Weise, PhD; and Valerie D. Callender, MD

Dr. Lain is with Sanova Dermatology in Austin, Texas. Messrs. Agrawal and Ruvolo are with Beiersdorf, Inc, IC in Florham Park, New Jersey. Dr. Weise is with Beiersdorf AG, Research and Development in Hamburg, Germany. Dr. Callender is with the Callendar Dermatology and Cosmetic Center in Glenn Dale, Maryland. 

FUNDING: This article was funded by an unrestricted educational grant from Beiersdorf.

DISCLOSURES: Dr. Lain has served as consultant and/or investigator for AbbVie, Aclaris Therapeutics Inc., AlfaSigma, Allergan Inc., Almirall, Arcutis, AstraZeneca, Athenix, Biofrontera, Biopelle Inc., BioPharmX, Biorasi LLC, Bristol Myers Squibb, Brickell Biotech Inc., Cassiopea S.p.A., Castle Biosciences, Celgene, Cellceutix, ChemoCentryx, Concert Pharma, Cutanea Life Sciences, Demira, Dermavant, Dermtech, Dow Pharmaceutical Sciences Inc., Dr Reddy’s Laboratory, Eli Lily, EPI Health, Endo Pharma, Evelo, Gage Development Company LLC, Galderma Laboratories, LP, Hovione, Incyte, Janssen, Johnson & Johnson, Kadmon Corporation LLC, La Roche-Posay Laboratorie Pharmaceutique, LEO Laboratories Ltd., Medimmune, Menlo Therapeutics, Mindera, Neothetics, Nielsen Holdings NV, Novartis, Ortho Dermatologics, Pierre Fabre, Pfizer Inc, Promius Pharma LLC, Sanofi, Sebacia Inc., Sienna Labs Inc., SkinCeuticals LLC, Sol-Gel Technologies, SUN Pharma, Symatese Timber Pharma, UCB, Valeant Pharmaceuticals North America LLC, and Vyne Therapeutics, and is a stockholder in Moleculin LLC; Agrawal, Ruvolo, and Dr. Weise are employees of Beiersdorf; Dr. Callender has served as an investigator and/or received grants from AbbVie/Allergan, Almirall, Aerolase, Arcutis, Avava, Beiersdorf, Eirion, Eli Lilly, Janssen, L’Oréal, Pfizer, Prollenium, Skinbetter Science, Symatese, Teoxane; as a consultant or advisor for Acne Store, Aerolase, Arcutis, Avita Medical, Beiersdorf, Cutera, Dermavant, EPI Health, Jeune Aesthetics, L’Oréal, OrthoDerm, Scientis, Sente, SkinCeuticals, UCB; as a speaker for Eli Lilly, L’Oréal, SkinCeuticals; and has received royalties from Elsevier and UpToDate.

Introduction

Over-the-counter (OTC) skincare products formulated to prevent and minimize signs of aging skin have proliferated in recent years as the understanding of aging mechanisms has advanced. Cutaneous aging is determined by intrinsic as well as extrinsic factors­—with ultraviolet (UV) radiation the main cause of accelerated skin aging.¹ Mitochondrial dysfunction, leading to impaired cellular energy metabolism and cellular senescence, represent two essential hallmarks of skin aging.^2–5 The changes in metabolic homeostasis are accompanied by visible structural changes and signs of skin aging, including wrinkles, fine lines, and loss of elasticity, among other signs.^3,6 Generation of reactive oxygen species (ROS), reactive nitrogen species (RNS) and other free radicals causes further damage to skin cells and the extracellular matrix, and impairs cellular energy metabolism.⁶ These highly active molecules, which are generated secondary to deregulation in cellular respiration, are also associated with exposure to external insults, such as UV radiation.^6–8 This starts a vicious cycle: the skin’s energy metabolism is disturbed, accompanied by increased formation of free radicals; as a result, the skin cells need increasing amounts of energy for repair and protection.^1,6–8

Ubiquitous throughout the body, coenzyme Q10 (CoQ10) is an endogenous lipophilic molecule with a central role in cellular energy metabolism—more specifically, the mitochondrial electron transport chain. Additionally, CoQ10 functions as an effective antioxidant molecule involved in neutralization of reactive species and other free radicals.^6,9–12 CoQ10 levels in the skin decrease with age and exposure to UV radiation.^6,12–14 Topical supplementation of CoQ10 has been shown to ameliorate signs of skin aging both by stabilizing mitochondrial activity and by exerting antioxidant properties, which typically translates to regeneration of skin processes involved in cutaneous skin aging.^6,15,16 

Given the variety of skincare products available, it is important for dermatology healthcare professionals to have a thorough knowledge of active ingredients such as CoQ10 to educate and advise patients. Because many patients feel that maintaining a youthful and pleasant facial appearance is important, facial aging can impact quality of life.

In the present review, we discuss the currently available literature supporting use of CoQ10 in anti-aging topical skincare products.

Discussion

Cellular metabolism and cutaneous aging. Skin aging involves a variety of factors, encompassing chronological processes as well as exposure to factors in the environment, lifestyle, and chronic disease that impair overall function (Figure 1).^3,15,19 The interaction of these intrinsic and extrinsic factors leads to metabolic and molecular changes, including deteriorating cellular and extracellular structures and reduction of the skin’s ability to regenerate and maintain appropriate homeostasis.^1,9,20 

Clinically, cutaneous aging is characterized by thinning skin, loss of elasticity, and increased wrinkling.^2,20,21 Pigmentation changes can occur (e.g., lentigines and other pigmentation), veins and bones can become more visible, and injuries take longer to heal.^2,20 Cellular activity decreases at a molecular level, collagen production decreases while degradation increases, and there is an increase in nonfunctional elastic fibers.^2,12,22 Deterioration of mitochondrial function leads to ROS generation, often overwhelming cellular redox homeostasis, thereby causing further damage to cellular structures and to the extracellular matrix, including collagen.^2,13 Aging epidermal keratinocytes may also shift energy generation from aerobic respiration to anaerobic glycolysis, a change that has been attributed to an attempt to compensate for reduced CoQ10 levels.³⁵ Cells may also enter a state of cellular senescence, or irreversible growth arrest.^2,21,23–25

Skin cells are continuously involved in repairing and regenerating tissue; these processes generally require a high amount of energy, along with well-regulated cellular metabolism to withstand exposure to external and internal stressors.²¹ The intrinsic aging process is driven by oxygen free radicals (ROS); these molecules damage cellular and extracellular structures, including DNA and lipid membranes, and upregulate matrix metalloproteinases (MMPs). The net result is increased cutaneous breakdown and reduced levels of collagen and elastin.^3,21,26 The subsequent imbalance is known as oxidative stress, which occurs due to an imbalance between ROS and endogenous antioxidants.³ The most common oxygen species are hydrogen peroxide, singlet oxygen, and hydroxyl radicals.¹² Accumulation of ROS results in inflammation, cellular senescence, and skin aging.³ To defend against this, the skin has enzymatic and non-enzymatic antioxidant mechanisms. Enzymes that help prevent radical damage can include superoxide dismutase (SOD), catalase, and glutathione peroxidase, while non-enzymatic antioxidants present in skin include vitamin E, ascorbate (vitamin C), and CoQ10, which has a dual action as an antioxidant and energy metabolizer.¹²

Mechanism of action of CoQ10. The structure of CoQ10 is similar to vitamin K, but it can be synthesized in the body (Figure 2).²⁷ In the skin, CoQ10 functions as both an integral part of cellular energy metabolism and as a barrier against ROS. Skin’s CoQ10 level decreases with age, declining through the ages of 20 to 66 years (Figure 3); this decline contributes to an age-dependent metabolic alteration.⁶ Low CoQ10 can be associated with oxidative stress, mitochondrial dysfunction, and cellular senescence in dermal fibroblasts, resulting in a disruption of cellular homeostasis.^12,23,25 

Cellular respiration. CoQ10 has an essential physiological role as a cofactor for mitochondrial enzyme pathways within cells.²⁸ Even small increases in CoQ10 concentrations in the inner mitochondrial membrane are thought to lead to increased respiration.²⁸ Alterations in mitochondrial function impair cellular adenosine triphosphate (ATP) production and thereby inhibit the fuel for cellular repair mechanisms and function (Figure 4).²⁸ As a consequence, ROS accumulate, which in turn can damage mitochondria, cellular membranes, and mitochondrial DNA, accelerating skin aging in a negative feedback loop.²⁸ In response to reduced mitochondrial energy generation, other sources of intracellular energy—such as switchover to anaerobic pathways—attempt to compensate.^{28, 35} Anaerobic pathways, such as glycolysis, favor formation of advanced glycation end products, which also may harm cellular processes, including generation of nonfunctional cytoskeletal proteins, inflammation, and potentially, cellular apoptosis. This sequence highlights why it is important to preserve mitochondrial energy generation.²⁸ The ability of CoQ10 to positively impact mitochondrial function underlies its ability to maintain appropriate energy levels.^6,12,23,25 In turn, this helps prevent aging skin from converting to anaerobic energy production.^{28, 29}

Antioxidant function. Outside of the mitochondria, CoQ10 in its reduced form acts as an antioxidant to stabilize cellular membranes by protecting against peroxidation of phospholipids.^{12,13,28, 30} In addition, it may slow the chain propagation of ROS and regenerates oxidized vitamin C and vitamin E.^31,32 CoQ10 sustains skin function against free radicals and their ability to activate the mitogen-activated protein kinase (MAPK) pathway. Activation of MAPK stimulates production of MMPs, including collagenases, which damage collagen fibers.^36–38 Finally, CoQ10 reduces damage caused by lipid peroxidase to lipids, proteins, and DNA.^14,26 Overall, the unique dual functionality of CoQ10 in skin may stimulate collagen production, primarily via its energetic function in delivering ATP for synthesis, and also mitigate skin aging by protecting mitochondrial function and decreasing the activity of reactive oxygen species.³

Anti-aging evidence of Coq10. Anti-aging benefits associated with CoQ10 have been shown in early aging and in mature skin.²⁷ In 1999, Hoppe et al¹² showed that CoQ10 not only penetrated into the living layers of human skin to reduce oxidation, but also reduced the depth of wrinkles following topical application around the skin of the eyes for six months (n=20). In addition, these researchers found that CoQ10 reduced collagenase expression in human dermal fibroblasts exposed to UV radiation.¹² Hoppe et al also showed that CoQ10 had no cytotoxicity in cultured keratinocytes, even at concentrations much higher than used in skincare products.¹² Further, its irritancy potential was similar to vehicle (e.g., absent) even in individuals with sensitive skin.^12,33 A reduction in wrinkle depth was also shown by Ashida et al,¹⁷ while Innui et al³⁶ demonstrated that CoQ10 decreases production of cytokines by keratinocytes, which in turn reduces MMPs and associated wrinkles. 

Using x-ray fluorescence and iodine labeling, Staufer et al³⁴ assessed cellular uptake and distribution of CoQ10 in vitro in human skin cells.³⁴ After exogenous application, there was a large accumulation of CoQ10 in skin cells.³⁴ Schniertshauer¹⁶ further demonstrated increased mitochondrial respiration—along with ATP production—in human epidermis samples after exogenous CoQ10 administration. Similar findings were reported by Knott et al,⁶ along with reduction of ROS and increase in antioxidative capacity. Marcheggiani et al²³ showed that CoQ10 supplementation improved cellular oxidative status, and conversely, inhibition of CoQ10 is associated with a shift toward a senescent phenotype in skin cells, indicating CoQ10 is not a sidebar to skin aging but rather a main cause.²⁵ Prahl et al³⁵ demonstrated that CoQ10 application protected and stabilized function of mitochondria against UV irradiation.

In 2020, Mine et al³⁹ showed that CoQ10 application increased proliferation of fibroblasts and mRNA expression of collagen (types I, II and VII), elastin, and heat shock protein 47. Additionally, Marcheggiani et al²³ revealed that in a CoQ10 deprivation model, the cells with reduced CoQ10 levels enter cellular senescence and secrete inflammatory cytokines as well as show reduced collagen and elastin expression. These effects can be reversed by CoQ10 replenishment (Figure 5).²⁵ Collagen and elastin are both important to maintain skin structure and function, and decreases are associated with wrinkle formation that is accelerated by both aging and UV exposure.³⁶ Further, CoQ10 inhibited MMP expression and subsequent collagen degradation.³⁶ 

Most recently, a skincare product containing CoQ10 was evaluated, with ultra-weak photon emission and corneometer, after application on the forearm of 30 female subjects aged 35 to 60 years with dry skin (44%) or normal skin (66%).⁴⁰ This unpublished study was a controlled (non-treated site) and blinded evaluation in which the CoQ10 skincare product  improved antioxidative status, as indicated by decreased UVA-induced ultra-weak photon emission after one (T1) and two (T2) weeks of regular application, and increased skin moisturization on Corneometer® assessments. The ultra-weak photon emission or chemiluminescence is described in Liebel et al.⁴¹ Figure 6 shows the ultra-weak photon emission. In addition, the test product was well tolerated by the study population, with no discomfort observed or reported for any subject. 

In an unpublished, split-face, randomized, blinded study of a CoQ10 skincare product applied twice daily for four weeks, effects on periorbital skin wrinkling versus untreated skin (n=41) were compared. Study participants were women aged 38 to 66 years with facial lines and wrinkles of any severity and Fitzpatrick Skin Phototypes I to IV. The evaluated CoQ10 product was associated with improvements in both wrinkle roughness and wrinkle depth as assessed by facial-wrinkle-analysis in high definition with FOITS_HD technique, an optical method for non-contact measurement of skin microtopography (Figure 7).⁴² In this study, after two weeks the untreated area had increased for the Rz (ten-point mean roughness) and Ra (arithmetical mean roughness) parameters by about 8 to 10 percent in comparison to baseline. After four weeks, increases for Rz and Ra parameters by about 4 to 5 percent were observed. For the test product formulated with CoQ10, after four weeks, decrease for Rz and Ra parameters were observed. Figure 7 shows the continuous improvement in skin roughness with the use of the CoQ10-based formula. 

In another unpublished study, 36 women aged 40 or older, with Fitzpatrick Skin Phototypes I to IV, were enrolled.⁴³ Subjects included in the study had at least mild to moderate crepey skin on the neck, décolletage, dorsal forearms, and back of the hands. Overall, expert grader ratings showed that the product formulated with CoQ10 was associated with improvement in crepey skin and wrinkles after both two and four weeks of use compared to baseline (Figure 8). Pinch/recoil data from the back of the hand showed a large improvement in elasticity after both two and four weeks of use compared to baseline. 

Limitations. The strength of the current review is limited by the fact that the data from the last three unpublished clinical studies discussed in this review^40,42,43 are not publicly available in the literature. More published clinical studies evaluating the efficacy of the CoQ10 skincare product that is discussed here should be conducted to confirm the results of these internally conducted clinical studies. 

Conclusion

As described in this paper, CoQ10’s dual functionality—as both a key component of cellular energy metabolism and as a powerful antioxidant—are favorable attributes when utilized in topical supplementation formulations. CoQ10 is present in the skin’s own molecules, but its amount decreases with age. Topical CoQ10 replenishment is well tolerated by most skin types, including sensitive skin, allowing for a broader use of the ingredient for patients with most skin types.^6,12 The energy metabolism and antioxidative effects of CoQ10 support its daily use. In the clinical studies described here, we observed the anti-aging benefits of use of CoQ10. In a four-week study, an improvement in skin facial roughness and wrinkles was reported. In areas with crepey skin on the neck or the back of the hand, clinical improvement was documented. 

CoQ10 has been shown to penetrate the skin following topical application and to be highly effective at protecting against skin damage at the cellular level while improving signs of cutaneous aging.⁶ It has actions that target both intrinsic aging and extrinsic aging. Further, CoQ10 is safe and has very low irritation potential, including in individuals with sensitive skin.¹²

References:

1. Farage MA, Miller KW , Maibach HI. Textbook of aging skin. Berlin: Springer; 2010.
2. Danczak-Pazdrowska A, Gornowicz-Porowska J, Polanska A, et al. Cellular senescence in skin-related research: targeted signaling pathways and naturally occurring therapeutic agents. Aging Cell. 2023:e13845.
3. Qian H, Shan Y, Gong R, et al. Mechanism of action and therapeutic effects of oxidative stress and stem cell-based materials in skin aging: current evidence and future perspectives. Front Bioeng Biotechnol. 2022;10:1082403.
4. Tigges J, Krutmann J, Fritsche E, et al. The hallmarks of fibroblast ageing. Mech Ageing Dev. 2014;138:26–44.
5. Lopez-Otin C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell. 2013;153:1194–217.
6. Knott A, Achterberg V, Smuda C, et al. Topical treatment with coenzyme Q10-containing formulas improves skin’s Q10 level and provides antioxidative effects. Biofactors. 2015;41:383–390.
7. Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol. 1956;11:298–300.
8. Zwerschke W MS, Stock IP, et al. Metabolic analysis of senescent human fibroblasts reveals a role for AMP in cellular senescence. Biochem J. 2003;376:403–411.
9. Genova ML, Lenaz G. New developments on the functions of coenzyme Q in mitochondria. Biofactors. 2011;37:330–354.
10. Garrido-Maraver J, Cordero MD, Oropesa-Avila M, et al. Coenzyme Q10 therapy. Mol Syndromol. 2014;5:187–197.
11. Sguizzato M, Mariani P, Spinozzi F, et al. Ethosomes for Coenzyme Q10 cutaneous administration: From design to 3D skin tissue evaluation. Antioxidants (Basel). 2020;9.
12. Hoppe U, Bergemann J, Diembeck W, et al. Coenzyme Q10, a cutaneous antioxidant and energizer. Biofactors. 1999;9:371–378.
13. Ayunin Q, Miatmoko A, Soeratri W, et al. Improving the anti-ageing activity of coenzyme Q10 through protransfersome-loaded emulgel. Sci Rep. 2022;12:906
14. Tessema EN, Bosse K, Wohlrab J, et al. Investigation of ex vivo Skin Penetration of Coenzyme Q10 from Microemulsions and Hydrophilic Cream. Skin Pharmacol Physiol. 2020;33:293–299.
15. Blatt T, Lenz H, Koop U, et al. Stimulation of skin’s energy metabolism provides multiple benefits for mature human skin. Biofactors. 2005;25:179–185.
16. Schniertshauer D, Gebhard D, Bergemann J. Age-dependent loss of mitochondrial function in epithelial tissue can be reversed by Coenzyme Q(10). J Aging Res. 2018;2018:6354680.
17. Ashida Y, Yamanishi H, Terada T, et al. CoQ10 supplementation elevates the epidermal CoQ10 level in adult hairless mice. Biofactors. 2005;25:175–178.
18. Berneburg M, Gremmel T, Kurten V, et al. Creatine supplementation normalizes mutagenesis of mitochondrial DNA as well as functional consequences. J Invest Dermatol. 2005;125:213–220.
19. Bravo B, Correia P, Goncalves Junior JE, et al. Benefits of topical hyaluronic acid for skin quality and signs of skin aging: From literature review to clinical evidence. Dermatol Ther. 2022;35:e15903.
20. Zorina A, Zorin V, Isaev A, et al. Dermal fibroblasts as the main target for skin anti-age correction using a combination of regenerative medicine methods. Curr Issues Mol Biol. 2023;45:3829–3847.
21. Shin SH, Lee YH, Rho NK, et al. Skin aging from mechanisms to interventions: focusing on dermal aging. Front Physiol. 2023;14:1195272.
22. Rovero P, Malgapo DMH, Sparavigna A, et al. The clinical evidence-based paradigm of topical anti-aging skincare formulations enriched with bio-active peptide SA1-III (KP1) as collagen modulator: from bench to bedside. Clin Cosmet Investig Dermatol. 2022;15:2693–2703.
23. Marcheggiani F, Kordes S, Cirilli I, et al. Anti-ageing effects of ubiquinone and ubiquinol in a senescence model of human dermal fibroblasts. Free Radic Biol Med. 2021;165:282–288.
24. Vidali S, Feichtinger RG, Emberger M, et al. Ageing is associated with a reduction in markers of mitochondrial energy metabolism in the human epidermis. Exp Dermatol. 2023;32:900–905.
25. Marcheggiani F, Cirilli I, Orlando P, et al. Modulation of Coenzyme Q(10) content and oxidative status in human dermal fibroblasts using HMG-CoA reductase inhibitor over a broad range of concentrations. From mitohormesis to mitochondrial dysfunction and accelerated aging. Aging (Albany NY). 2019;11:2565–2582.
26. Imhof L, Leuthard D. Topical Over-the-counter anti-aging agents: an update and systematic review. Dermatology. 2021;237:217–229.
27. Huang ZR, Lin YK, Fang JY. Biological and pharmacological activities of squalene and related compounds: potential uses in cosmetic dermatology. Molecules. 2009;14:540–554.
28. Blatt T, Littarru GP. Biochemical rationale and experimental data on the antiaging properties of CoQ(10) at skin level. Biofactors. 2011;37:381–385.
29. Singh B, Schoeb TR, Bajpai P, et al. Reversing wrinkled skin and hair loss in mice by restoring mitochondrial function. Cell Death Dis. 2018;9:735.
30. Federico A, Cardaioli E, Da Pozzo P, et al. Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci. 2012;322:254–262.
31. Littarru GPL, P. Coenzyme Q10: multiple benefits in one ingredient. OCL. 2011;18:76–82.
32. Navas P, Villalba JM, de Cabo R. The importance of plasma membrane coenzyme Q in aging and stress responses. Mitochondrion. 2007;7 Suppl:S34–S40.
33. Coverly J, Peters L, Whittle E, et al. Susceptibility to skin stinging, non-immunologic contact urticaria and acute skin irritation; is there a relationship? Contact Dermatitis. 1998;38:90–95.
34. Staufer T, Schulze ML, Schmutzler O, et al. Assessing cellular uptake of exogenous coenzyme Q(10) into human skin cells by X-ray fluorescence imaging. Antioxidants (Basel). 2022;11.
35. Prahl S, Kueper T, Biernoth T, et al. Aging skin is functionally anaerobic: importance of coenzyme Q10 for anti aging skin care. Biofactors. 2008;32:245–255.
36. Inui M, Ooe M, Fujii K, et al. Mechanisms of inhibitory effects of CoQ_{10} on UVB-induced wrinkle formation in vitro and in vivo. BioFactors. 2008;32:237–243. 
37. Bank G, Kagan D, Madhavi D. Coenzyme Q10: clinical update and bioavailability. J Evid Based Integr Med. 2011;16(2):129–137
38. Vaghari H, Vaghari R, Jafarizadeh-Malmiri H et al. Coenzyme Q10 and its effective sources. Am J Biochem Biotechnol. 2016:(12) 214–219.
39. Mine Y, Takahashi T, Okamoto T. Stimulatory effects of collagen production induced by coenzyme Q(10) in cultured skin fibroblasts. J Clin Biochem Nutr. 2022;71:29–33.
40. Data on File Beiersdorf Study Report STDR-071541C.
41. Liebel F,  Kaur S, Ruvolo E, et al. Irradiation of skin with visible light induces reactive oxygen species and matrix-degrading enzymes. J Invest Dermatol. 2012;132(7):1901–1907.
42. Data on File Beiersdorf Study Report STDR-072057C. 
43. Data on File Beiersdorf Study Report STDR-077530C.