If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
It has long been noticed by dermatologists that acne patients have reduced skin aging, often observed many years after the acne has recovered. Signs of aging, such as wrinkling and skin thinning, appear later in acne patients compared with nonaffected individuals. This was speculated to be due to increased sebum secretion during the lifetime, but other factors are likely involved (
In this study, we investigated leucocyte telomere length (LTL) in subjects with acne compared with control subjects using data from the TwinsUK registry (http://www.twinsuk.ac.uk/).
Telomeres are repeat TTAGGG sequences at the end of linear chromosomes guarding against loss of genetic material during cellular replication. Repeated cell cycles eventually lead to a critically shortened LTL, signaling cellular senescence and triggering apoptosis. Hence, LTL has been shown to be predictive of biological aging (
Volunteers in the TwinsUK cohort were not recruited on the basis of any specific trait or disease and have been shown to have diseases and lifestyle characteristics similar to those of the general population (
). Guy’s and St. Thomas’ Hospital NHS Trust Research Ethics Committee approved the study, and all twins provided informed written consent. For historical reasons the TwinsUK registry involves mainly women, and men were therefore excluded from this study. The history of acne was self-reported during a nurse-administered questionnaire, and the female twins were asked if they had ever suffered from acne and whether their acne was self-treated, treated by a general physician or treated by a dermatologist (
) (see Supplementary Materials online for details). Mean LTL in the 1,205 subjects was 7.08 kilobase pairs (kb) (median = 7.06 kb, range = 5.70–8.67 kb). Mean weight was 67 kg (median = 65 kg, range = 40–115 kg), and mean height was 162 cm (median = 162 cm, range = 144–182 cm). The mean age of the twins at the time of DNA extraction was 48 ± 12 years.
Linear regression (see Supplementary Materials for details) showed that samples from acne patients had longer LTL (mean = 7.17 ± 0.64 kb) compared with those from control subjects (mean = 6.92 ± 0.02 kb) after adjustment for age, twin relatedness, weight, and height (β = 0.11; standard error = 0.05; P = 0.01). Using score tests under a logistic regression model, we further investigated the association between acne and a set of single-nucleotide polymorphisms (SNPs) previously reported to be associated with LTL in a sample of 1,893 patients with severe acne and 5,132 population controls from the UK Acne Genetic study (
). No LTL SNPs were significantly associated with acne after correction for multiple testing. However, rs3027234 in the CTC1 gene was nominally significant (see Supplementary Table S1 online). Finally, we performed a mixed-effect logistic regression analysis in whole-genome data from healthy skin samples comparing acne patients and control subjects. The expression data was measured in 705 women from the TwinsUK registry (http://www.muther.ac.uk/), of whom 346 had data on acne history. We selected 195 control twins who were perfectly age-matched to 39 twins with acne and gene expression data (see Supplementary Materials for details). Only the ZNF420 gene (probe ILMN_1720431) was significantly associated with acne history at a false discovery rate of 5%, showing a higher expression in control subjects (P = 7.73 × 10–7) (Table 1 and Figure 1). ZNF420 is one of the 30% most expressed genes in skin.
Table 1Whole-genome differential expression between acne patients and control subjects using a mixed linear model to control for intrapair phenotypic correlation
The table reports the top 20 hits from the mixed-effect logistic regression analysis. P-values, Storey Q-value, effect sizes (β), and standard errors are reported. Only the ZNF420 gene remained significant after multiple testing at 5% false discovery rate (Q < 0.05).
7.73 × 10-7
1.54 × 10-4
9.01 × 10-4
1.01 × 10-3
1.14 × 10-3
1.17 × 10-3
1.23 × 10-3
1.35 × 10-3
1.42 × 10-3
1.45 × 10-3
1.66 × 10-3
1.78 × 10-3
1.93 × 10-3
2.10 × 10-3
2.18 × 10-3
2.22 × 10-3
2.22 × 10-3
2.22 × 10-3
2.22 × 10-3
2.37 × 10-3
Abbreviation: SE, standard error.
1 The table reports the top 20 hits from the mixed-effect logistic regression analysis. P-values, Storey Q-value, effect sizes (β), and standard errors are reported. Only the ZNF420 gene remained significant after multiple testing at 5% false discovery rate (Q < 0.05).
This study investigated reduced skin aging observed in acne by assessing telomere length in circulating white blood cells and gene expression in the skin. Acne patients had longer telomeres after adjusting for age, height, and twin relatedness, suggesting that the delayed skin aging may be due to reduced senescence. Only one SNP predicting LTL was found to be associated with acne at nominal significance. This SNP is located within the CTC1 gene, which is a component of the CST complex and plays an important role in protecting telomeres against degradation (
). The reduced expression of the gene ZNF420, which encodes the protein Apak, in the normal skin of acne patients suggests that p53 is up-regulated in acne patients, because the ZNF420 gene is a negative regulator of p53-mediated apoptosis.
Considering longer telomeres and the up-regulation of the p53 pathway in acne patients, it could be speculated that acne susceptibility may be linked to the biology of cancer. A recent study from the Nurses; Health study II, a large US cohort involving more than 99,000 female nurses (
). Additionally, recent genome-wide association studies have reported significant associations between acne and genes involved in cancer susceptibility, including the MYC gene and genes linked to the transforming growth factor-β cell signaling pathway (
). Further work is needed to investigate the associations between cell senescence, acne, and cancer susceptibility, but this work sheds light on this very common and often debilitating skin disease.
Conflict of Interest
The authors state no conflict of interest.
We wish to express our appreciation to all study participants of TwinsUK. MS, AV, and MF wish to acknowledge S. Burbidge of the Imperial College High-Performance Computing service for his assistance.
TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, and the National Institute for Health Research-funded BioResource, Clinical Research Facility, and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. MF, VB, and AV are supported by BSF grant no. 5044i.