INTRODUCTION
Retinol, or all-trans retinol, was the first vitamin to be synthesized in a laboratory. Methods of synthesis came from the work of David Adrianne van Dorf and Jozef Ferdinand Arens in 1947.3
Research into the effects of topical retinol on skin was started in the early 1960’s by Albert Kligman and others, but instability of the molecule prevented it from reaching its full potential. It was not until the 1990’s that cosmetic chemists were able to stabilize retinol in formulation leading to a resurgence of research on this molecule.4 in addition to retinol, a variety of retinol derivatives referred to as retinoids, were developed and commercialized for topical application. Topical retinoids have been used as pharmacotherapy for acne, psoriasis, hyperkeratotic disorders, rosacea, and as anti-aging agents (Figure 1). In this review, we will focus on the cosmetic retinoids and make the case for retinol as the ideal retinoid for treating aging skin.
Skin aging is a result of the cumulative effects of intrinsic and extrinsic aging. Intrinsic aging, or natural aging, is a progressive degeneration of the skin over time and causes skin to be pale, thin, fragile, dry, and finely wrinkled. Extrinsic aging is a result of exposure to a variety of factors referred to as the exposome.5 The exposome includes environmental factors such as ultraviolet light, infrared and visible light, pollution, and cigarette smoking and internal factors like nutrition, sleep, and stress. While all these play a role, ultraviolet light has the most profound effect on skins appearance. Photoaged skin has a distinct phenotype characterized by a deep coarse wrinkling, laxity, mottled hyperpigmentation, lentigines, leathery appearance, telangiectasia, and sallowness. Oxidative stress plays a central role in both intrinsic and extrinsic aging but is greatly upregulated by UV exposure.6 Chromophores in the skin produce an array of reactive oxygen species (ROS) upon exposure to UV light that are toxic at high concentrations. The oxidative stress that ensues triggers downstream signaling that induces collagen breakdown by metalloproteinases (MMPs) and reduces collagen production.7 This collagen deficit impairs the mechanical and functional properties of the dermis resulting in exaggerated skin wrinkling. Melanin pigments are photoprotective and upregulated by UV exposure causing mottled hyperpigmentation and lentigines. The appearance of aging skin is a primary cosmetic concern and there is a rise in consumer demand for affordable and accessible topical treatments. This has led to an increasing investment in research and development by major cosmetic companies in search of effective over the counter skincare solutions.
The efficacy of retinoic acid or tretinoin for treating aging skin was confirmed in the hairless mouse model and in clinical trials in the 1980’s. Histologic evaluation of mice irradiated with UV and treated with tretinoin showed a significantly wider zone of reconstructed dermal collagen in the papillary dermis when compared to vehicle controls.8 Several small studies published at this time demonstrate tretinoin improves
Research into the effects of topical retinol on skin was started in the early 1960’s by Albert Kligman and others, but instability of the molecule prevented it from reaching its full potential. It was not until the 1990’s that cosmetic chemists were able to stabilize retinol in formulation leading to a resurgence of research on this molecule.4 in addition to retinol, a variety of retinol derivatives referred to as retinoids, were developed and commercialized for topical application. Topical retinoids have been used as pharmacotherapy for acne, psoriasis, hyperkeratotic disorders, rosacea, and as anti-aging agents (Figure 1). In this review, we will focus on the cosmetic retinoids and make the case for retinol as the ideal retinoid for treating aging skin.
Skin aging is a result of the cumulative effects of intrinsic and extrinsic aging. Intrinsic aging, or natural aging, is a progressive degeneration of the skin over time and causes skin to be pale, thin, fragile, dry, and finely wrinkled. Extrinsic aging is a result of exposure to a variety of factors referred to as the exposome.5 The exposome includes environmental factors such as ultraviolet light, infrared and visible light, pollution, and cigarette smoking and internal factors like nutrition, sleep, and stress. While all these play a role, ultraviolet light has the most profound effect on skins appearance. Photoaged skin has a distinct phenotype characterized by a deep coarse wrinkling, laxity, mottled hyperpigmentation, lentigines, leathery appearance, telangiectasia, and sallowness. Oxidative stress plays a central role in both intrinsic and extrinsic aging but is greatly upregulated by UV exposure.6 Chromophores in the skin produce an array of reactive oxygen species (ROS) upon exposure to UV light that are toxic at high concentrations. The oxidative stress that ensues triggers downstream signaling that induces collagen breakdown by metalloproteinases (MMPs) and reduces collagen production.7 This collagen deficit impairs the mechanical and functional properties of the dermis resulting in exaggerated skin wrinkling. Melanin pigments are photoprotective and upregulated by UV exposure causing mottled hyperpigmentation and lentigines. The appearance of aging skin is a primary cosmetic concern and there is a rise in consumer demand for affordable and accessible topical treatments. This has led to an increasing investment in research and development by major cosmetic companies in search of effective over the counter skincare solutions.
The efficacy of retinoic acid or tretinoin for treating aging skin was confirmed in the hairless mouse model and in clinical trials in the 1980’s. Histologic evaluation of mice irradiated with UV and treated with tretinoin showed a significantly wider zone of reconstructed dermal collagen in the papillary dermis when compared to vehicle controls.8 Several small studies published at this time demonstrate tretinoin improves
