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Generation of twenty four induced pluripotent stem cell lines from twenty four members of the Lothian Birth Cohort 1936.

ABSTRACT: Cognitive decline is among the most feared aspects of ageing. We have generated induced pluripotent stem cells (iPSCs) from 24 people from the Lothian Birth Cohort 1936, whose cognitive ability was tested in childhood and in older age. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating oriP/EBNA1 backbone plasmids expressing six iPSC reprogramming factors (OCT3/4 (POU5F1), SOX2, KLF4, L-Myc, shp53, Lin28, SV40LT). All lines demonstrated STR matched karyotype and pluripotency was validated by multiple methods. These iPSC lines are a valuable resource to study molecular mechanisms underlying individual differences in cognitive ageing and resilience to age-related neurodegenerative diseases.

SUBMITTER: Toombs J

PROVIDER: S-EPMC7347008 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Generation of twenty four induced pluripotent stem cell lines from twenty four members of the Lothian Birth Cohort 1936.

Toombs Jamie J Panther Lindsay L Ornelas Loren L Liu Chunyan C Gomez Emilda E Martín-Ibáñez Raquel R Cox Simon R SR Ritchie Stuart J SJ Harris Sarah E SE Taylor Adele A Redmond Paul P Russ Tom C TC Murphy Lee L Cooper James D JD Burr Karen K Selvaraj Bhuvaneish T BT Browne Cathy C Svendsen Clive N CN Cowley Sally A SA Deary Ian J IJ Chandran Siddharthan S Spires-Jones Tara L TL Sareen Dhruv D

Stem cell research 20200520

Cognitive decline is among the most feared aspects of ageing. We have generated induced pluripotent stem cells (iPSCs) from 24 people from the Lothian Birth Cohort 1936, whose cognitive ability was tested in childhood and in older age. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating oriP/EBNA1 backbone plasmids expressing six iPSC reprogramming factors (OCT3/4 (POU5F1), SOX2, KLF4, L-Myc, shp53, Lin28, SV40LT). All lines demonstrated STR matched karyotype and p ...[more]

PMID: 32450543

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Project description: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.

Dataset Information

Generation of twenty four induced pluripotent stem cell lines from twenty four members of the Lothian Birth Cohort 1936.

Publications

Generation of twenty four induced pluripotent stem cell lines from twenty four members of the Lothian Birth Cohort 1936.

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