DNA methylation (DNAm)-based biomarkers of aging have been developed for many tissues and organs. However, these biomarkers have sub-optimal accuracy in fibroblasts and other cell types used in ex vivo studies. To address this challenge, we developed a novel and highly robust DNAm age estimator (based on 391 CpGs) for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva samples. High age correlations can also be observed in sorted neurons, glia, brain, liver, and even bone samples. Gestational age correlates with DNAm age in cord blood. When used on fibroblasts from Hutchinson Gilford Progeria Syndrome patients, this age estimator (referred to as the skin & blood clock) uncovered an epigenetic age acceleration with a magnitude that is below the sensitivity levels of other DNAm-based biomarkers. Furthermore, this highly sensitive age estimator accurately tracked the dynamic aging of cells cultured ex vivo and revealed that their proliferation is accompanied by a steady increase in epigenetic age. The skin & blood clock predicts lifespan and it relates to many age-related conditions. Overall, this biomarker is expected to become useful for forensic applications (e.g. blood or buccal swabs) and for a quantitative ex vivo human cell aging assay.

Sunlight-exposure recommendations are inappropriate for individuals of South Asian ethnicity who live at the UK latitude. More guidance is required to meet the vitamin D requirements of this sector of the population. This study was registered at www.isrctn.org as ISRCTN 07565297.

SummaryBackgroundThe concurrent impact of repeated low‐level summer sunlight exposures on vitamin D production and cutaneous DNA damage, potentially leading to mutagenesis and skin cancer, is unknown.ObjectivesThis is an experimental study (i) to determine the dual impact of repeated low‐level sunlight exposures on vitamin D status and DNA damage/repair (via both skin and urinary biomarkers) in light‐skinned adults; and (ii) to compare outcomes following the same exposures in brown‐skinned adults.MethodsTen white (phototype II) and six South Asian volunteers (phototype V), aged 23–59 years, received 6 weeks’ simulated summer sunlight exposures (95% ultraviolet A/5% ultraviolet B, 1·3 standard erythemal doses three times weekly) wearing summer clothing exposing ~35% body surface area. Assessments made were circulating 25‐hydroxyvitamin D [25(OH)D], immunohistochemistry for cyclobutane pyrimidine dimer (CPD)‐positive nuclei and urinary biomarkers of direct and oxidative (8‐oxo‐deoxyguanosine) DNA damage.ResultsSerum 25(OH)D rose from mean 36·5 ± 13·0 to 54·3 ± 10·5 nmol L−1 (14·6 ± 5·2 to 21·7 ± 4·2 ng mL−1) in phototype II vs. 17·2 ± 6·3 to 25·5 ± 9·5 nmol L−1 (6·9 ± 2·5 to 10·2 ± 3·8 ng mL−1) in phototype V (P < 0·05). Phototype II skin showed CPD‐positive nuclei immediately postcourse, mean 44% (range 27–84) cleared after 24 h, contrasting with minimal DNA damage and full clearance in phototype V (P < 0·001). The findings did not differ from those following single ultraviolet radiation (UVR) exposure. Urinary CPDs remained below the detection threshold in both groups; 8‐oxo‐deoxyguanosine was higher in phototype II than V (P = 0·002), but was unaffected by UVR.ConclusionsLow‐dose summer sunlight exposures confer vitamin D sufficiency in light‐skinned people concurrently with low‐level, nonaccumulating DNA damage. The same exposures produce minimal DNA damage but less vitamin D in brown‐skinned people. This informs tailoring of sun‐exposure policies.

Vulval ACD affects women of a wide age range, and presents with nonspecific symptoms such as pruritus and/or vulval irritation. Patients may have experienced symptoms for many years before presenting to a dermatologist. The diagnosis of vulval ACD is more common in those who have been exposed to many potential sensitizers.

This article reviews recent data on the expression, regulation and activation of antimicrobial peptides (AMP) in human skin, and considers their potential protective and pro-inflammatory roles following upregulation by ultraviolet radiation (UVR). Antimicrobial peptides are small peptides that are key components of the innate immune system, originally identified by their vital role in protecting the body-environment interface from infection. However, it has now become clear that AMP have more extensive actions, including the provision of pivotal links with the adaptive immune system. Moreover, aberrant AMP expression may contribute to immuno-modulated inflammatory dermatoses including psoriasis, eczema and the photoaggravated condition lupus erythematosus. Recent work has demonstrated the direct upregulation of AMP in healthy skin by cutaneous UVR exposure. This may serve to protect the skin from risks imposed by both the biophysical barrier-compromise and the immunosuppression that are attributable to UVR exposure. Furthermore, it is observed that UVR provokes upregulation of AMP in an atypical manner in the photosensitivity disorder polymorphic light eruption. Dysregulated UVR responses of these pro-inflammatory proteins may play a role in the pathogenesis of certain immune-mediated diseases caused or aggravated by sunlight.

Increasing evidence regarding positive effects of exposure to sunlight has led to suggestions that current advice may be overly weighted in favour of avoidance. UV-A has been reported to lower blood pressure, possibly through nitric oxide (NO) production in skin. Here, we set out to investigate effects of UV-A and solar-simulated radiation on the potential source of dermal NO, the effective doses and wavelengths, the responsiveness of different human skin cells, the magnitude of inter-individual differences and the potential influence of age. We utilised isogenic keratinocytes, microvascular endothelial cells, melanocytes and fibroblasts isolated from 36 human skins ranging from neonates to 86 years old. We show that keratinocytes and microvascular endothelial cells show greatest NO release following biologically relevant doses of UV-A. This was consistent across multiple neonatal donors and the effect is maintained in adult keratinocytes. Our observations are consistent with a bi-phasic mechanism by which UV-A can trigger vasodilatory effects. Analyses of NO-production spectra adds further evidence that nitrites in skin cells are the source of UV-mediated NO release. These potentially positive effects of ultraviolet radiation lend support for objective assessment of environmental influence on human health and the idea of “healthy sun exposure”.

Photosensitive patients are, through their photoprotective measures, at high risk of year-round low vitamin D status. Guidance on oral measures should target this patient group and their physicians.

These results verify that MIS on the head and neck can spread significantly beyond the clinical margin and demonstrate the importance of confirming clearance histologically before closure procedures. Mohs micrographic surgery has the advantage of total margin evaluation and where available it may be reasonable to start with a 5-mm margin. Where MMS is not a treatment option, the authors would advocate larger excision margins of ≥10 mm.