DNA methylation outlier burden, health and ageing in Generation Scotland and the Lothian Birth Cohorts of 1921 and 1936

BackgroundDNA methylation outlier burden has been suggested as a potential marker of biological age. An outlier is typically defined as DNA methylation levels at any one CpG site that are three times beyond the inter-quartile range from the 25th or 75th percentiles compared to the rest of the population. DNA methylation outlier burden (the number of such outlier sites per individual) increases exponentially with age. However, these findings have been observed in small samples.ResultsHere, we showed an association between age and log10-transformed DNA methylation outlier burden in a large cross-sectional cohort, the Generation Scotland Family Health Study (N = 7010, β = 0.0091, p < 2 × 10−16), and in two longitudinal cohort studies, the Lothian Birth Cohorts of 1921 (N = 430, β = 0.033, p = 7.9 × 10−4) and 1936 (N = 898, β = 0.0079, p = 0.074). Significant confounders of both cross-sectional and longitudinal associations between outlier burden and age included white blood cell proportions, body mass index (BMI), smoking, and batch effects. In Generation Scotland, the increase in epigenetic outlier burden with age was not purely an artefact of an increase in DNA methylation level variability with age (epigenetic drift). Log10-transformed DNA methylation outlier burden in Generation Scotland was not related to self-reported, or family history of, age-related diseases, and it was not heritable (SNP-based heritability of 4.4%, p = 0.18). Finally, DNA methylation outlier burden was not significantly related to survival in either of the Lothian Birth Cohorts individually or in the meta-analysis after correction for multiple testing (HRmeta = 1.12; 95% CImeta = [1.02; 1.21]; pmeta = 0.021).ConclusionsThese findings suggest that, while it does not associate with ageing-related health outcomes, DNA methylation outlier burden does track chronological ageing and may also relate to survival. DNA methylation outlier burden may thus be useful as a marker of biological ageing

Mobility and Ageing: a review of interactions between transport and technology from the perspective of older people

This chapter is an overview of the issues for older people in relation to transport and technology. I demonstrate that mobility and technology are intertwined in complex ways, and that non-transport technologies may impact older people’s experience and achievement of mobility. Understanding the nexus between mobility, information and communication technologies and older people can help us design accessible and acceptable technologies to support well-being and health in older age. This matters because new ICT is increasingly relied on to support service delivery in both the public and private sectors. Older people are heterogeneous, with different attitudes, levels of income and education affecting technology uptake. Age-related cognitive and physical impairments can also impact on technology adoption. The chapter concludes with how age-friendly design principles can support active ageing