Intradermal nevi with atypical nuclei in the elderly: The senescent nevus

Boyd, Alan S.; Chen, Sheau-Chiann; Shyr, Yu

doi:10.1016/j.jaad.2015.06.013

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…Using this same model, here we demonstrate that UVB-induced senescence of melano-cytes recapitulates several mechanisms observed in fibroblasts such as cell cycle arrest characterized by activation and stabilization of the p53-p21 pathway and disappearance of the nuclear protein Lamin B1, increased activity of SA-β-Gal, impairment of the ubiquitin-proteasome system and activation of autophagy. In addition, UVB irradiation increased the frequency of multinucleated melanocytes, an event already reported to be related to senescence of these cells and to the occurrence of pigmentation disorders by other investigators ( Boyd et al, 2015 ; Leikam et al, 2015 ).…”

Section: Discussionsupporting

confidence: 58%

A new model to investigate UVB-induced cellular senescence and pigmentation in melanocytes

Martic

Wedel

Jansen‐Dürr

et al. 2020

Mechanisms of Ageing and Development

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Ultraviolet (UV) light is known to potentially damage human skin and accelerate the skin aging process. Upon UVB exposure, melanocytes execute skin protection by increasing melanin production. Senescent cells, including senescent melanocytes, are known to accumulate in aged skin and contribute to the age-associated decline of tissue function. However, melanocyte senescence is still insufficiently explored. Here we describe a new model to investigate mechanisms of UVB-induced senescence in melanocytes and its role in photoaging. Exposure to mild and repeated doses of UVB directly influenced melanocyte proliferation, morphology and ploidy. We confirmed UVB-induced senescence with increased senescence-associated β-galactosidase positivity and changed expression of several senescence markers, including p21, p53 and Lamin B1. UVB irradiation impaired proteasome and increased autophagic activity in melanocytes, while expanding intracellular melanin content. In addition, using a co-culture system, we could confirm that senescence-associated secretory phenotype components secreted by senescent fibroblasts modulated melanogenesis. In conclusion, our new model serves as an important tool to explore UVB-induced melanocyte senescence and its involvement in photoaging and skin pigmentation.

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Section: Discussionsupporting

confidence: 58%

A new model to investigate UVB-induced cellular senescence and pigmentation in melanocytes

Martic

Wedel

Jansen‐Dürr

et al. 2020

Mechanisms of Ageing and Development

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“…The number of nevi peaks around 40 years of age, and with increased age, there is a progressive decrease in the number of common and atypical nevi (Ortonne, 1990; Schäfer et al, 2006). Over several years, epidermal nevus cells migrate to the dermis, losing melanocyte differentiation markers (Aso et al., 1988; Boyd et al., 2015; Clark et al., 1984). However, it is unknown whether the nevus cells remain in the dermis or are eventually removed by phagocytosis or apoptosis.…”

Section: Aging‐induced Dermal and Epidermal Changesmentioning

confidence: 99%

Alterations of the pigmentation system in the aging process

Kang

Lee

Papaccio

et al. 2021

Pigment Cell Melanoma Res

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Human skin aging is a natural phenomenon that results from continuous exposure to intrinsic (time, genetic factors, hormones) as well as extrinsic factors (UV exposure, pollution, tobacco). In areas that are frequently exposed to the sun, photoaging blends with the process of intrinsic aging, resulting in an increased senescent cells number and consequently accelerating the aging process. The severity of photodamage depends on constitutional factors, including skin phototype (skin color, tanning capacity), intensity, and duration of sunlight/UV exposure. Aging affects nearly every aspect of cutaneous biology, including pigmentation. Clinically, the phenotype of age pigmented skin has a mottled, uneven color, primarily due to age spots, with or without hypopigmentation. Uneven pigmentation might be attributed to the hyperactivation of melanocytes, altered distribution of pigment, and turnover. In addition to direct damage to pigment‐producing cells, photodamage alters the physiological crosstalk between keratinocytes, fibroblasts, endothelial cells, and melanocytes responsible for natural pigmentation homeostasis. Interestingly, age‐independent diffuse expression of senescence‐associated markers in the dermal and epidermal compartment is also associated with vitiligo, suggesting that premature senescence plays an important role in the pathology.

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“…Therefore, some of the morphologic changes are likely to be secondary to ultraviolet light exposure. The cytologic atypia may resemble that seen in "nevi with senescent atypia" [21] or nevi with "bizarre atypia" [22]. However, in both cases, there is no clear correlation of the presence of such atypical cells and depth within the lesion (both entities are described as having atypical cells dispersed through the entire depth of the nevi).…”

Section: Discussionmentioning

confidence: 99%

Detection of a MicroRNA molecular signature of ultraviolet radiation in the superficial regions of melanocytic nevi on sun-exposed skin

Bell

Chakravarti

et al. 2018

Modern Pathology

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How melanocytes transform into melanoma cells remains largely unknown. However, prolonged ultraviolet radiation exposure is linked with melanoma, and the DNA of melanomas arising in chronically sun-exposed skin is characterized by an elevated number of pyrimidine transitions, mainly C>T (predominantly caused by ultraviolet B), and transversions of GC>TA or AT>CG (caused by ultraviolet A over indirect mechanisms). Since ultraviolet penetrates mostly only the superficial dermis, we sought to determine the extent to which superficial and deep melanocytes of nevi in sun-exposed skin differ in their miRNA expression and consider the changes as likely secondary to ultraviolet radiation-induced damage. The differentially expressed miRNAs were analyzed for known potential oncomiRs or linked to potential oncogenes or tumor suppressors. Superficial and deep melanocytes were microdissected from the nevi of 14 patients. The suspensions were processed for hybridization to a ribonucleotide protection system with 2280 total probes, including 2256 miRNA probes targeting 2083 human miRNAs. A comprehensive analysis of all human miRNAs registered in miRBase 11.0 was performed using the HTG Molecular Diagnostic database. Statistical analysis of these data yielded for 14 samples a statistically relevant profile of 39 miRNA species at FDR<0.1 that were differentially expressed between superficial and deep melanocytes. Ingenuity Pathway Analysis based on the expression data of these 39 miRNAs suggested the gene transcripts AR, MDM2, SMAD2/3, and YBX1 as the most probable miRNA targets, which were validated at the protein level. Our findings suggest that superficial ultraviolet radiation-damaged melanocytes can be differentiated from deep melanocytes on the basis of the expression of 39 miRNAs, the most probable gene transcript and protein targets of which are AR, MDM2, SMAD2/3, and YBX1, with YBX1 expression validating the best the molecular signature in immunohistochemical analysis.

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Intradermal nevi with atypical nuclei in the elderly: The senescent nevus

Cited by 6 publications

References 22 publications

A new model to investigate UVB-induced cellular senescence and pigmentation in melanocytes

A new model to investigate UVB-induced cellular senescence and pigmentation in melanocytes

Alterations of the pigmentation system in the aging process

Detection of a MicroRNA molecular signature of ultraviolet radiation in the superficial regions of melanocytic nevi on sun-exposed skin

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