How To Reduce Hyperpigmentation by Targeting Cellular Senescence

7 min read

May 2, 2023
May 02,2023
SKIN SCIENCE, ONESKIN PRODUCTS

How To Reduce Hyperpigmentation by Targeting Cellular Senescence

7 min read

May 2, 2023
May 02,2023
SKIN SCIENCE, ONESKIN PRODUCTS
Suddenly seeing sun spots on your skin? This is a telltale sign of hyperpigmentation, a common skin condition caused by the overproduction of melanin, the pigment that gives color to your skin, hair, and eyes. Regardless of your skin tone, hyperpigmentation can pop up as you get older and be incredibly difficult to treat.For decades, the skin care industry has focused on exfoliating ingredients and harsh resurfacing treatments to help brighten the appearance of hyperpigmentation. But is this really the right approach? Let’s take a closer look at the science behind hyperpigmentation– and why addressing the root cause of excess skin pigment may be a smarter solution to sun spots.
Suddenly seeing sun spots on your skin? This is a telltale sign of hyperpigmentation, a common skin condition caused by the overproduction of melanin, the pigment that gives color to your skin, hair, and eyes. Regardless of your skin tone, hyperpigmentation can pop up as you get older and be incredibly difficult to treat.For decades, the skin care industry has focused on exfoliating ingredients and harsh resurfacing treatments to help brighten the appearance of hyperpigmentation. But is this really the right approach? Let’s take a closer look at the science behind hyperpigmentation– and why addressing the root cause of excess skin pigment may be a smarter solution to sun spots.
01

What is skin hyperpigmentation?

Hyperpigmentation is a common skin condition that results in the darkening of patches of skin. It can look different on different people– from small dark spots to large patches of darkened skin.
01

What is skin hyperpigmentation?

Hyperpigmentation is a common skin condition that results in the darkening of patches of skin. It can look different on different people– from small dark spots to large patches of darkened skin.
02

What causes hyperpigmentation?

Melanin is the overarching term for a group of pigments that occur in human hair, skin, and eyes. The darker your skin tone or hair, the more melanin your body produces. Melanin is made by special cells called melanocytes, which produce and transfer melanin pigments to neighboring cells.(1)Hyperpigmentation occurs when our melanocytes go into overdrive, producing lots and lots of melanin that collects in the skin. While scientists believe that the body creates melanin as a protective measure against sun damage, the exact biological purpose of overactive melanin production is still not entirely clear.(1) Part of the mystery is that while the majority of hyperpigmentation occurs due to unprotected sun exposure, not all hyperpigmentation is related to UV rays.Hormonal shifts caused by pregnancy, menopause or certain medications can also cause hyperpigmentation. The reason skin creates more melanin in response to these hormonal shifts isn’t fully known.Additionally, inflammatory skin conditions like acne and eczema can cause injury to the skin that then triggers the skin to produce more melanin. This is called post-inflammatory hyperpigmentation or PIH.(2)
02

What causes hyperpigmentation?

Melanin is the overarching term for a group of pigments that occur in human hair, skin, and eyes. The darker your skin tone or hair, the more melanin your body produces. Melanin is made by special cells called melanocytes, which produce and transfer melanin pigments to neighboring cells.(1)Hyperpigmentation occurs when our melanocytes go into overdrive, producing lots and lots of melanin that collects in the skin. While scientists believe that the body creates melanin as a protective measure against sun damage, the exact biological purpose of overactive melanin production is still not entirely clear.(1) Part of the mystery is that while the majority of hyperpigmentation occurs due to unprotected sun exposure, not all hyperpigmentation is related to UV rays.Hormonal shifts caused by pregnancy, menopause or certain medications can also cause hyperpigmentation. The reason skin creates more melanin in response to these hormonal shifts isn’t fully known.Additionally, inflammatory skin conditions like acne and eczema can cause injury to the skin that then triggers the skin to produce more melanin. This is called post-inflammatory hyperpigmentation or PIH.(2)
03

Why do we see more hyperpigmentation as we age?

As we age, our skin becomes less efficient at producing and evenly distributing melanin throughout the skin. At the center of this phenomenon is cellular senescence, the accumulation of cells at the end of their life cycle that induce aging in neighboring cells. Senescent cells come in all forms – including senescent melanocytes. As these cells accumulate in aged skin, they contribute to accelerated, age-associated hyperpigmentation.(3)
03

Why do we see more hyperpigmentation as we age?

As we age, our skin becomes less efficient at producing and evenly distributing melanin throughout the skin. At the center of this phenomenon is cellular senescence, the accumulation of cells at the end of their life cycle that induce aging in neighboring cells. Senescent cells come in all forms – including senescent melanocytes. As these cells accumulate in aged skin, they contribute to accelerated, age-associated hyperpigmentation.(3)
04

What are common treatments for hyperpigmentation?

Hyperpigmentation leaves many of us scrambling for the beauty aisle or a derm appointment looking for a solution. For many years, most of the available solutions have included harsh exfoliants, which help brighten hyperpigmentation by bringing excess melanin to the surface of the skin where it is sloughed away. Common solutions include:
  • Chemical peels: A chemical peel involves applying a chemical solution to the skin to remove the top layer of dead skin cells. This can help reduce the appearance of hyperpigmentation by shedding melanin-rich skin at the surface of the skin and bringing deeper melanin deposits to the surface. Whether at-home or in-office, most chemical peels are mild and result in only temporary redness, dryness and peeling. For deep hyperpigmentation, dermatologists may recommend intensive in-office peels that require a longer period of healing and more painful side effects.
  • Laser therapy: Laser therapy uses high-energy light to target and break up the pigmented cells in the skin, which are then absorbed by the body's immune system. Depending on the type of laser used, side effects may include a mild, sunburned sensation to more pronounced pain and redness for a period of days. Some lasers are not recommended for deeper skin tones and may actually trigger further hyperpigmentation, so it’s important to find a skilled practitioner for your skin tone.
  • Microdermabrasion: This treatment involves using a device to exfoliate the top layer of skin. Like other forms of exfoliation, repeated treatments can help reduce the appearance of hyperpigmentation. Side effects include temporary redness and irritation. As with laser treatments, it’s important to find a skilled practitioner to avoid causing skin injury that can actually increase melanin production.
  • Topical creams: Over-the-counter or prescription creams containing hydroquinone, kojic acid, or retinoids are commonly used to help reduce the appearance of hyperpigmentation. Unfortunately, many of these active ingredients come with difficult downsides. Hydroquinone, in particular, while very effective at reducing hyperpigmentation, can cause irritation and a side effect called ochronosis, which results in blue-black or gray-blue discoloration.(4) Similarly, kojic acid and retinol treatments may be difficult to tolerate for people with sensitive or dry skin–triggering redness, irritation, and skin peeling.
04

What are common treatments for hyperpigmentation?

Hyperpigmentation leaves many of us scrambling for the beauty aisle or a derm appointment looking for a solution. For many years, most of the available solutions have included harsh exfoliants, which help brighten hyperpigmentation by bringing excess melanin to the surface of the skin where it is sloughed away. Common solutions include:
  • Chemical peels: A chemical peel involves applying a chemical solution to the skin to remove the top layer of dead skin cells. This can help reduce the appearance of hyperpigmentation by shedding melanin-rich skin at the surface of the skin and bringing deeper melanin deposits to the surface. Whether at-home or in-office, most chemical peels are mild and result in only temporary redness, dryness and peeling. For deep hyperpigmentation, dermatologists may recommend intensive in-office peels that require a longer period of healing and more painful side effects.
  • Laser therapy: Laser therapy uses high-energy light to target and break up the pigmented cells in the skin, which are then absorbed by the body's immune system. Depending on the type of laser used, side effects may include a mild, sunburned sensation to more pronounced pain and redness for a period of days. Some lasers are not recommended for deeper skin tones and may actually trigger further hyperpigmentation, so it’s important to find a skilled practitioner for your skin tone.
  • Microdermabrasion: This treatment involves using a device to exfoliate the top layer of skin. Like other forms of exfoliation, repeated treatments can help reduce the appearance of hyperpigmentation. Side effects include temporary redness and irritation. As with laser treatments, it’s important to find a skilled practitioner to avoid causing skin injury that can actually increase melanin production.
  • Topical creams: Over-the-counter or prescription creams containing hydroquinone, kojic acid, or retinoids are commonly used to help reduce the appearance of hyperpigmentation. Unfortunately, many of these active ingredients come with difficult downsides. Hydroquinone, in particular, while very effective at reducing hyperpigmentation, can cause irritation and a side effect called ochronosis, which results in blue-black or gray-blue discoloration.(4) Similarly, kojic acid and retinol treatments may be difficult to tolerate for people with sensitive or dry skin–triggering redness, irritation, and skin peeling.
05

The OS-01 peptide may address hyperpigmentation better than common topical alternatives

Given the downsides of topical hyperpigmentation treatments, our scientists decided to test if our proprietary OS-01 peptide could outperform kojic acid and retinoic acid (retinol) in the lab.Because the OS-01 peptide has been scientifically proven to reduce cellular senescence (5) -- a root cause of hyperpigmentation -- our scientists hypothesized that it would actually reduce source of hyperpigmentation more effectively than topical treatments that only treat surface-level symptoms.The study was performed in three steps:
  1. Induce hyperpigmentation: To induce melanin production in human skin cells in vitro, our scientists exposed melanocytes to IBMX (isobutylmethylxanthine), a molecule that mimics one of the main pathways induced by UV radiation and also imitates a pathway induced by ACTH (adrenocorticotropic hormone), a hormone that is thought to be one of the main factors behind melasma.
  2. Expose melanocytes to different treatments: After the melanocytes were exposed to IBMX to induce melanin production, we treated the melanocytes with either nothing (positive control), retinoic acid, kojic acid, or the OS-01 peptide.
  3. Measure resulting melanin production: Finally, we measured the amount of melanin production both intracellularly (inside the cells) and extracellularly (outside of the cells).
05

The OS-01 peptide may address hyperpigmentation better than common topical alternatives

Given the downsides of topical hyperpigmentation treatments, our scientists decided to test if our proprietary OS-01 peptide could outperform kojic acid and retinoic acid (retinol) in the lab.Because the OS-01 peptide has been scientifically proven to reduce cellular senescence (5) -- a root cause of hyperpigmentation -- our scientists hypothesized that it would actually reduce source of hyperpigmentation more effectively than topical treatments that only treat surface-level symptoms.The study was performed in three steps:
  1. Induce hyperpigmentation: To induce melanin production in human skin cells in vitro, our scientists exposed melanocytes to IBMX (isobutylmethylxanthine), a molecule that mimics one of the main pathways induced by UV radiation and also imitates a pathway induced by ACTH (adrenocorticotropic hormone), a hormone that is thought to be one of the main factors behind melasma.
  2. Expose melanocytes to different treatments: After the melanocytes were exposed to IBMX to induce melanin production, we treated the melanocytes with either nothing (positive control), retinoic acid, kojic acid, or the OS-01 peptide.
  3. Measure resulting melanin production: Finally, we measured the amount of melanin production both intracellularly (inside the cells) and extracellularly (outside of the cells).
Shown in skin cells (melanocytes) in vitro , comparing the effects of the OS-01 peptide to retinoic acid and kojic acid on intracellular and extracellular melanin production.
The results of our study were astounding. While all three treatments reduced melanin production, the OS-01 peptide reduced melanin production significantly more – demonstrating its potential superiority in reducing skin hyperpigmentation.Not only can the OS-01 peptide address melanin production more effectively, it can also do so without the irritating side effects commonly seen with retinoic acid and kojic acid. In fact, the OS-01 peptide has been shown to greatly improve skin health markers by increasing skin’s epidermal thickness, improving skin’s barrier function, and increasing key biomarkers associated with production of collagen and hyaluronic acid. (5) This data indicates that the OS-01 peptide could be a superior topical method for supporting an even skin tone and long-term skin health.
Shown in skin cells (melanocytes) in vitro , comparing the effects of the OS-01 peptide to retinoic acid and kojic acid on intracellular and extracellular melanin production.
The results of our study were astounding. While all three treatments reduced melanin production, the OS-01 peptide reduced melanin production significantly more – demonstrating its potential superiority in reducing skin hyperpigmentation.Not only can the OS-01 peptide address melanin production more effectively, it can also do so without the irritating side effects commonly seen with retinoic acid and kojic acid. In fact, the OS-01 peptide has been shown to greatly improve skin health markers by increasing skin’s epidermal thickness, improving skin’s barrier function, and increasing key biomarkers associated with production of collagen and hyaluronic acid. (5) This data indicates that the OS-01 peptide could be a superior topical method for supporting an even skin tone and long-term skin health.
Key Takeaways:
  • Hyperpigmentation is an age-related condition in which excess melanin collects in deposits around the skin.
  • While hyperpigmentation can be triggered by UV exposure or hormones, it commonly appears later in life as a result of increased cellular senescence.
  • Common topical treatments like kojic acid, retinol, and hydroquinone have risks including irritation, skin aging and skin discoloration or darkening.
  • In a study comparing retinoic acid, kojic acid, and OneSkin’s OS-01 peptide, OS-01 notably outperformed all other treatments in its ability to reduce melanin content in skin (shown in lab studies on human skin samples).
  • This result may be due in part to the OS-01 peptide’s proven ability to reduce cellular senescence, as shown in lab studies on ex vivo human skin samples. (3)
Key Takeaways:
  • Hyperpigmentation is an age-related condition in which excess melanin collects in deposits around the skin.
  • While hyperpigmentation can be triggered by UV exposure or hormones, it commonly appears later in life as a result of increased cellular senescence.
  • Common topical treatments like kojic acid, retinol, and hydroquinone have risks including irritation, skin aging and skin discoloration or darkening.
  • In a study comparing retinoic acid, kojic acid, and OneSkin’s OS-01 peptide, OS-01 notably outperformed all other treatments in its ability to reduce melanin content in skin (shown in lab studies on human skin samples).
  • This result may be due in part to the OS-01 peptide’s proven ability to reduce cellular senescence, as shown in lab studies on ex vivo human skin samples. (3)
References
  1. WebMD https://www.webmd.com/a-to-z-guides/what-is-melanin
  2. Healthline https://www.healthline.com/health/hyperpigmentation#types
  3. ScienceDirect https://www.sciencedirect.com/science/article/pii/S0047637420301184
  4. NCBI https://www.ncbi.nim.nih.gov/books/NBK539693/
  5. Zonari, A., et al. Senotherapeutic peptide treatment reduces biological age and senescence burden in human skin models. Npj Aging, 9(1), 1-15. 2023.
References
  1. WebMD https://www.webmd.com/a-to-z-guides/what-is-melanin
  2. Healthline https://www.healthline.com/health/hyperpigmentation#types
  3. ScienceDirect https://www.sciencedirect.com/science/article/pii/S0047637420301184
  4. NCBI https://www.ncbi.nim.nih.gov/books/NBK539693/
  5. Zonari, A., et al. Senotherapeutic peptide treatment reduces biological age and senescence burden in human skin models. Npj Aging, 9(1), 1-15. 2023.

Reviewed by Alessandra Zonari, PhD, Chief Scientific Officer (CSO) and Co-Founder of OneSkin

Alessandra earned her Master’s degree in stem cell biology, and her PhD in skin regeneration and tissue engineering at the Federal University of Minas Gerais in Brazil in collaboration with the 3B’s Research Group in Portugal. Alessandra did a second post-doctoral at the University of Coimbra in Portugal. She is a co-inventor of three patents and has published 20 peer-reviewed papers in scientific journals.

Reviewed by Alessandra Zonari, PhD, Chief Scientific Officer (CSO) and Co-Founder of OneSkin

Alessandra earned her Master’s degree in stem cell biology, and her PhD in skin regeneration and tissue engineering at the Federal University of Minas Gerais in Brazil in collaboration with the 3B’s Research Group in Portugal. Alessandra did a second post-doctoral at the University of Coimbra in Portugal. She is a co-inventor of three patents and has published 20 peer-reviewed papers in scientific journals.

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