Life Extension Magazine®
Skin DNA structures being supported by retinol

Retinol Blend Reverses Skin Aging

Retinol in a gradual-release system, combined with two other retintoids, has been shown to reduce crow’s feet by 44%, repair sun damage, and reduce fine lines and wrinkles.

Scientifically reviewed by: Dr. Amanda Martin, DC, on July 2020. Written By Robert Goldfaden and Gary Goldfaden, MD.

Many skin creams and serums have temporary effects.

But retinol can initiate changes in the skin that turn back the clock on skin aging.

Once applied to the skin, retinol converts into retinoic acid,1 a compound that sends signals to skin cells that stop and even repair skin aging.

Researchers have found that retinoic acid:

  • Stimulates collagen and elastin synthesis,2,3
  • Boosts moisture,4
  • Promotes tissue repair,5 and
  • Combats solar radiation.6

Many topical creams contain retinol. But retinol is just one of a group of compounds called retinoids, which have slightly different effects.

These retinol compounds have been shown to:7,8

  • Reduce crow’s feet by 44%,
  • Decrease mottled pigmentation by 84%,
  • Prevent and even repair sun damage, and
  • Reduce fine lines and wrinkles in just 14 days.

A lipid-soluble delivery system allows retinol to be gradually released in the skin to restore a smoother, more youthful appearance, with fewer side effects.

How Skin Ages

Woman holding her hand up to block sun

Skin naturally ages over time,9,10 but there are ways to partially rebel.

The epidermis, the outer layer of the skin, becomes thinner, which weakens the barrier function. That leads to increased moisture loss and vulnerability to environmental threats.11,12

In the second layer of skin, the dermis, there is reduced function and number of the specialized cells known as fibroblasts.13,14 This diminishes the output of the structural proteins collagen and elastin, which give skin its firmness and elasticity, and of hyaluronic acid, responsible for keeping skin hydrated.

All these changes make skin appear dry, pale, and blemished, and lead to fine wrinkles.

Skin aging is accelerated by environmental factors, especially prolonged sun exposure.

Ultraviolet radiation activates enzymes that break down dermal structural proteins and cause DNA damage that slows the production of new skin cells.15-17

Sun-damaged skin is characterized by rough texture, deep wrinkles, age spots, and dark patches.

There’s a way to repair skin damage.

Retinol, retinyl palmitate, and hydroxypinacolone retinoate are vitamin A derivatives that belong to a group known as retinoids.

These retinoids enhance the ability of aged, damaged skin to restore itself.

Retinol Enhances Skin Renewal

Younger skin represented in layers

When retinol is topically applied to normal, aged skin, it increases the number of epidermal keratinocytes by 12-fold (keratinocytes produce the key structural protein keratin).18

That boosts the thickness of the epidermis, strengthening the skin-barrier function crucial for keeping skin hydrated, soft, and youthful.

Topical retinol regenerates the dermis by increasing the number of protein-synthesizing fibroblasts and reducing secretion of protein-degrading enzymes.19

It also stimulates the synthesis of collagen, elastin, and fibronectin, proteins that make up the dermal matrix, which can be thought of as the skin’s scaffolding.

These retinol-induced effects can be seen in people after as little as seven days.19

All these changes lead to a visible impact.

One randomized, double-blind clinical trial showed that topical retinol significantly reduces fine wrinkles, roughness, and severity of changes in naturally aged skin after 24 weeks, compared to a placebo.20

These benefits were later confirmed in another controlled, clinical trial that found significant increases in collagen and water-binding hyaluronic acid in response to topical retinol, leaving participants with rehydrated, smooth, and rejuvenated skin.21

Numerous human studies have confirmed that topical retinol also breathes new life into photodamaged skin.21-23 In one study, 62 participants applied either retinol or a placebo to their face for one year. Compared to the untreated group, retinol decreased crow’s feet by 44% and reduced mottled pigmentation by 84%.7

Retinyl Palmitate Protects Against Sun Damage

Older skin represented in layers

Retinyl palmitate is the main retinoid in the epidermis.24

There, it absorbs harmful ultraviolet rays and blocks inflammation, lipid peroxidation, and DNA damage associated with premature aging and skin cancer.25,26

In people, topical application of retinyl palmitate before UV exposure was as effective as sunscreen in preventing erythema (skin reddening and inflammation) and thymine dimers, a marker of DNA damage.25 Another study confirmed its photoprotective effects on DNA.27

Additional research indicates that retinyl palmitate not only prevents but repairs the sun’s damaging effects on the skin.

In one randomized, clinical trial, people applied topical retinyl palmitate (combined with vitamin E and moisturizers) to their face, neck, décolletage, arms, and lower body for 12 weeks.28

At the study’s end, the face and neck areas of the treatment group had significant improvements in roughness, mottled pigmentation, coarse wrinkles, fine lines, and uneven skin tone compared to baseline and non-treatment groups.

The décolletage, arms, and lower legs also showed improvements in dryness, scaling, and crepey skin texture.28

What you need to know

Retinoids Rejuvenate Aging Skin

  • Over time, and with exposure to sun, our skin ages. This causes wrinkles, dryness, age spots, rough texture, and other visible signs of damage.
  • Applied topically, three related compounds called retinoids exert anti-aging effects.
  • Retinol renews the outer layers of the skin, reversing damage caused by time and UV radiation. It reduces wrinkles and crow’s feet, roughness, and mottled pigmentation.
  • Retinyl palmitate protects against photoaging by absorbing ultraviolet rays and inhibiting DNA damage. Applied before UV exposure, it’s shown to be as effective as sunscreen in preventing skin reddening and inflammation.
  • Hydroxypinacolone retinoate repairs damage and reduces fine lines and wrinkles similarly to prescription retinoic acid, but without irritation.
  • All three compounds are available in one topical formula.
  • A novel lipid-soluble delivery system allows retinol to be easily absorbed in the skin and released in a controlled manner, safely restoring hydrated, soft, and youthful skin.

Hydroxypinacolone Retinoate Repairs Skin

Retinol and retinyl palmitate each undergo several steps to be converted into retinoic acid.

A related compound, hydroxypinacolone retinoate, binds directly to retinoid receptors on skin cells, without needing to go through a conversion process.29

This allows hydroxypinacolone retinoate to provide similar benefits to prescription-only retinoic acid, but without its side effects (like peeling, redness, and hypersensitivity to the sun).

A topical formulation containing hydroxypinacolone retinoate was shown in humans to boost epidermal thickness by 26.3%, while significantly increasing the production of collagen, elastin, and fibronectin in the dermis to repair sun-damaged skin.30

In a separate human study, topical hydroxypinacolone retinoate reduced fine lines and wrinkles after 14 days —without skin irritation.8

Advanced Delivery System

Most topical products use a conventional delivery system that releases retinol all at once in the skin. This leads to the side effects people associate with retinol, such as redness and irritation.

A new delivery system encapsulates retinol in a solid matrix lipid structure. This enables it to be easily absorbed into the skin, then released in a controlled manner that minimizes side effects.31

Gradually releasing retinol into the skin maximizes its benefits and keeps skin smooth, hydrated, and youthful.

Summary

Three topical vitamin A derivatives—retinol, retinyl palmitate, and hydroxypinacolone retinoate—have been shown in human studies to protect and repair naturally aged and photodamaged skin.

A unique delivery system has been developed that ensures a gradual release of retinol in the skin to safely restore smooth, youthful, hydrated skin, without irritation.

If you have any questions on the scientific content of his article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.


Gary Goldfaden, MD, is a clinical dermatologist and lifetime member of the American Academy of Dermatology. He is the founder of Academy Dermatology in Hollywood, FL, and Cosmesis Skin Care. Dr. Goldfaden is a member of the Life Extension® Medical Advisory Board. All Cosmesis products are available online.


References

  1. Mukherjee S, Date A, Patravale V, et al. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety. Clin Interv Aging. 2006;1(4):327-48.
  2. Rossetti D, Kielmanowicz MG, Vigodman S, et al. A novel anti-ageing mechanism for retinol: induction of dermal elastin synthesis and elastin fibre formation. Int J Cosmet Sci. 2011 Feb;33(1):62-9.
  3. Kong R, Cui Y, Fisher GJ, et al. A comparative study of the effects of retinol and retinoic acid on histological, molecular, and clinical properties of human skin. J Cosmet Dermatol. 2016 Mar;15(1):49-57.
  4. Weiss JS, Ellis CN, Headington JT, et al. Topical tretinoin improves photoaged skin. A double-blind vehicle-controlled study. JAMA. 1988 Jan 22-29;259(4):527-32.
  5. Bhawan J. Short- and long-term histologic effects of topical tretinoin on photodamaged skin. Int J Dermatol. 1998 Apr;37(4):286-92.
  6. Fisher GJ, Wang ZQ, Datta SC, et al. Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med. 1997 Nov 13;337(20):1419-28.
  7. Randhawa M, Rossetti D, Leyden JJ, et al. One-year topical stabilized retinol treatment improves photodamaged skin in a double-blind, vehicle-controlled trial. J Drugs Dermatol. 2015 Mar;14(3):271-80.
  8. Available at: https://www.in-cosmetics.com/RXUK/RXUK_InCosmetics/2015-Website/Documents/in-cos15,%20IS,%20T2,D1,Granactive%20Retinoid%20The%20power%20of%20retinol%20without%20the%20irritation,John%20Gormley.pdf. Accessed June 2, 2020.
  9. Farage MA, Miller KW, Elsner P, et al. Intrinsic and extrinsic factors in skin ageing: a review. Int J Cosmet Sci. 2008 Apr;30(2):87-95.
  10. Baumann L. Skin ageing and its treatment. J Pathol. 2007 Jan;211(2):241-51.
  11. Farage MA, Miller KW, Elsner P, et al. Characteristics of the Aging Skin. Adv Wound Care (New Rochelle). 2013 Feb;2(1):5-10.
  12. Fenske NA, Lober CW. Structural and functional changes of normal aging skin. J Am Acad Dermatol. 1986 Oct;15(4 Pt 1):571-85.
  13. Varani J, Dame MK, Rittie L, et al. Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. Am J Pathol. 2006 Jun;168(6):1861-8.
  14. Quan T, Fisher GJ. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging: A Mini-Review. Gerontology. 2015;61(5):427-34.
  15. Pittayapruek P, Meephansan J, Prapapan O, et al. Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis. Int J Mol Sci. 2016 Jun 2;17(6).
  16. Panich U, Sittithumcharee G, Rathviboon N, et al. Ultraviolet Radiation-Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging. Stem Cells Int. 2016;2016:7370642.
  17. Lee CH, Wu SB, Hong CH, et al. Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy. Int J Mol Sci. 2013 Mar 20;14(3):6414-35.
  18. Shao Y, He T, Fisher GJ, et al. Molecular basis of retinol anti-ageing properties in naturally aged human skin in vivo. Int J Cosmet Sci. 2017 Feb;39(1):56-65.
  19. Varani J, Warner RL, Gharaee-Kermani M, et al. Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin. J Invest Dermatol. 2000 Mar;114(3):480-6.
  20. Kafi R, Kwak HS, Schumacher WE, et al. Improvement of naturally aged skin with vitamin A (retinol). Arch Dermatol. 2007 May;143(5):606-12.
  21. Tucker-Samaras S, Zedayko T, Cole C, et al. A stabilized 0.1% retinol facial moisturizer improves the appearance of photodamaged skin in an eight-week, double-blind, vehicle-controlled study. J Drugs Dermatol. 2009 Oct;8(10):932-6.
  22. Kikuchi K, Suetake T, Kumasaka N, et al. Improvement of photoaged facial skin in middle-aged Japanese females by topical retinol (vitamin A alcohol): a vehicle-controlled, double-blind study. J Dermatolog Treat. 2009;20(5):276-81.
  23. Sun M, Wang P, Sachs D, et al. Topical Retinol Restores Type I Collagen Production in Photoaged Forearm Skin within Four Weeks. Cosmetics. 2016;3(4):35.
  24. Yan J, Xia Q, Webb P, et al. Levels of retinyl palmitate and retinol in stratum corneum, epidermis and dermis of SKH-1 mice. Toxicol Ind Health. 2006 Apr;22(3):103-12.
  25. Antille C, Tran C, Sorg O, et al. Vitamin A exerts a photoprotective action in skin by absorbing ultraviolet B radiation. J Invest Dermatol. 2003 Nov;121(5):1163-7.
  26. Poljsak B, Dahmane R. Free radicals and extrinsic skin aging. Dermatol Res Pract. 2012;2012:135206.
  27. Sorg O, Tran C, Carraux P, et al. Spectral properties of topical retinoids prevent DNA damage and apoptosis after acute UV-B exposure in hairless mice. Photochem Photobiol. 2005 Jul-Aug;81(4):830-6.
  28. Rawlings AV, Stephens TJ, Herndon JH, et al. The effect of a vitamin A palmitate and antioxidant-containing oil-based moisturizer on photodamaged skin of several body sites. J Cosmet Dermatol. 2013 Mar;12(1):25-35.
  29. Antiaging effects of retinoid hydroxypinacolone retinoate on skin models. Journal of the American Academy of Dermatology. 2018 2018/09/01/;79(3):AB44.
  30. Truchuelo MT, Jimenez N, Miguel-Gomez L, et al. Histological and Immunohistochemical Evaluation of the Efficacy of a New Cosmetic Formulation in the Treatment of Skin Photoaging. Dermatol Res Pract. 2017;2017:8407247.
  31. Available at: https://www.aerreita.it/sites/default/files/files/brochure/KemSpheres_A3_112010.pdf. Accessed June 2, 2020.