The potential skin‐lightening candidate, senolytic drug ABT263, for photoageing pigmentation

Park, J.H.; Yoon, Jung Eun; Kim, Y.H.; Park, T.J.; Kang, Hee Young

doi:10.1111/bjd.20893

Cited by 10 publications

(13 citation statements)

References 8 publications

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“…Therefore, the elimination of senescent fibroblasts has the potential to improve photoaging-related skin pigmentation and re-lighten pigmented skin. The beneficial effects of senolytics in improving skin aging were recently demonstrated [ 129 , 130 ]. Topical rapamycin, an FDA-approved drug targeting the mTOR complex, reduces either the expression of the p16 INK4A protein consistent with a reduction in cellular senescence or the number of cells entering senescence with clinical improvements in aging skin [ 131 ].…”

Section: Therapeutic Strategy For Skin-aging Pigmentationmentioning

confidence: 99%

“…The aged mouse skin treated with ABT-263 or ABT-737 showed increased collagen density, epidermal thickness, and the proliferation of keratinocytes, as well as decreased levels of senescence-associated secretory phenotypes, such as MMP-1 and IL-6. Furthermore, Park et al [ 130 ] recently revealed that ABT-263 has anti-melanogenic effects and skin-lightening capabilities through their selective senolytic activity on senescent fibroblasts. ABT-737 also induced the clearance of senescent melanocytes in in vivo 3D human epidermal equivalents, subsequently preventing the neighboring cells from becoming senescent [ 132 ].…”

Section: Therapeutic Strategy For Skin-aging Pigmentationmentioning

confidence: 99%

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Skin-Aging Pigmentation: Who Is the Real Enemy?

Kim

Park

Kang

2022

Cells

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Skin aging is induced and sustained by chronological aging and photoaging. Aging skin pigmentation such as mottled pigmentation (senile lentigo) and melasma are typical signs of photoaging. The skin, like other human organs, undergoes cellular senescence, and senescent cells in the skin increase with age. The crosstalk between melanocytes as pigmentary cells and other adjacent types of aged skin cells such as senescent fibroblasts play a role in skin-aging pigmentation. In this review, we provide an overview of cellular senescence during the skin-aging process. The discussion also includes cellular senescence related to skin-aging pigmentation and the therapeutic potential of regulating the senescence process.

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Section: Therapeutic Strategy For Skin-aging Pigmentationmentioning

confidence: 99%

Section: Therapeutic Strategy For Skin-aging Pigmentationmentioning

confidence: 99%

Skin-Aging Pigmentation: Who Is the Real Enemy?

Kim

Park

Kang

2022

Cells

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“…Melanocyte senescence has recently been investigated as a driver of pigmentation disorders (reviewed in Kim et al, 2022) [ 47 ]. However, the role of senescent melanocytes themselves in pigmentary disorders appears to be limited, with melanin induction occurring in a paracrine manner, particularly from senescent fibroblasts which are known to induce senile lentigo and melasma [ 44 , 45 , 46 ].…”

Section: Melanocyte Senescencementioning

confidence: 99%

“…[ 35 , 36 , 37 ]. Senescent cells are also associated with human skin ageing phenotypes, for example epidermal thinning, wrinkles, melasma, and senile lentigo (colloquially known as age spots or liver spots) [ 11 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. There is increasing evidence to suggest that senescent melanocytes play a significant role in aged skin.…”

Section: Introductionmentioning

confidence: 99%

Current Understanding of the Role of Senescent Melanocytes in Skin Ageing

Hughes

Bishop

2022

Biomedicines

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Melanocytes reside within the basal epidermis of human skin, and function to protect the skin from ultraviolet light through the production of melanin. Prolonged exposure of the skin to UV light can induce irreparable DNA damage and drive cells into senescence, a sustained cell cycle arrest that prevents the propagation of this damage. Senescent cells can also be detrimental and contribute to skin ageing phenotypes through their senescence-associated secretory phenotype. Senescent cells can act in both an autocrine and paracrine manner to produce widespread tissue inflammation and skin ageing. Recently, melanocytes have been identified as the main senescent cell population within the epidermis and have been linked to a variety of skin ageing phenotypes, such as epidermal thinning and the presence of wrinkles. However, the literature surrounding melanocyte senescence is limited and tends to focus on the role of senescence in the prevention of melanoma. Therefore, this review aims to explore the current understanding of the contribution of senescent melanocytes to human skin ageing.

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“…However, several research studies have presented strong evidence that senescent dermal fibroblasts in melasma may evade immune cell clearance by the upregulation of lysophospholipids [6] and the non-classical major histocompatibility complex (MHC) molecule human leukocyte antigen (HLA)-E. [7] Encouragingly, recent studies have shown that the elimination of accumulated senescent fibroblasts using a non-invasive radiofrequency (RF) device or senolytic drugs significantly improves melasma and photoaging-related skin hyperpigmentation. [8,9] The sub-clinical telangiectatic erythema confined to melasma lesions is more often observed in certain patients [Supplementary Figure 1, http://links.lww.com/CM9/ B342], which represents an indicator that those patients are prone to rebound following treatment. [10] Senescent dermal fibroblasts have been reported to secrete vascular endothelial growth factor (VEGF) that directly stimulates neovascularization, and eventually these nascent endothelial cells release endothelin-1 that can upregulate the melanogenesis pathway in melanocytes.…”

mentioning

confidence: 99%