Accelerated epigenetic aging as a risk factor for chronic obstructive pulmonary disease and decreased lung function in two prospective cohort studies.

Chronic obstructive pulmonary disease (COPD) is a frequent diagnosis in older individuals and contributor to global morbidity and mortality. Given the link between lung disease and aging, we need to understand how molecular indicators of aging relate to lung function and disease. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we associated baseline epigenetic (DNA methylation) age acceleration with incident COPD and lung function. Models were adjusted for age, sex, smoking, height, weight, and baseline lung disease as appropriate. Associations were replicated in the Normative Aging Study. Of 770 KORA participants, 131 developed incident COPD over 7 years. Baseline accelerated epigenetic aging was significantly associated with incident COPD. The change in age acceleration (follow-up - baseline) was more strongly associated with COPD than baseline aging alone. The association between the change in age acceleration between baseline and follow-up and incident COPD replicated in the Normative Aging Study. Associations with spirometric lung function parameters were weaker than those with COPD, but a meta-analysis of both cohorts provide suggestive evidence of associations. Accelerated epigenetic aging, both baseline measures and changes over time, may be a risk factor for COPD and reduced lung function.

Fox-P3-positive regulatory T cells are present in the skin of generalized atopic eczema patients and are not particularly affected by medium-dose UVA1 therapy.

BACKGROUND: Regulatory T cells (T-reg cells) have been described as an important cell population in the UV treatment of inflammatory skin diseases. METHODS: We have treated five patients with generalized atopic eczema (AE) using medium-dose (15 cycles of 50 J/cm(2), total dose of 750 J/cm(2)) UVA1 therapy and have analyzed the skin-infiltrating T-cellular subsets before and after therapy. Skin biopsies were split for immunohistochemistry and Real-time PCR and analyzed for CD4, Fox-P3, GATA-3, and IL-10 transcription as well as for CD3, CD4, CD152, Fox-P3, and GITR staining. RESULTS: In all the investigated patients, we observed a good clinical response to UVA1. As described previously, the number of epidermal T cells slightly declined after irradiation. However, we did not observe a general decrease in T cell numbers. Within the population of T cells, no specific difference in the kinetics of Fox-P3-positive cells and Fox-P3-specific mRNA was noted as compared with GATA-3 positive T cells. These results were paralleled by RT-PCR for IL-10 and staining for CD152, a surface molecule that has been described for T-reg cells. CONCLUSION: In our hands, the clinical benefit of UVA1 treatment in AE patients does not seem to be due to a preferential survival/proliferation of T-reg cells.