Comparison of DNA Methylation Clocks in Black South African Men

Abstract

Aims: DNA methylation clocks are widely used to estimate biological age, although limited data are available on non-European ethnicities. This manuscript characterizes the behavior of five DNA methylation clocks in 120 older Black South African men. Methods: The age estimation accuracy of the Horvath, Hannum and skin and blood clocks and the relative age-related mortality risk and predicted time to death portrayed by the PhenoAge and GrimAge biomarkers are investigated, respectively. Results: The results confirm the tendency of DNA methylation clocks to underestimate the biological age of older individuals. GrimAge more accurately characterizes biological decline in this African cohort compared with PhenoAge owing to the unique inclusion of smoking-related damage in the GrimAge estimate. Conclusions: Each clock provides a different fraction of information regarding the aging body. It is essential to continue studying under-represented population groups to ensure methylation-derived indicators are robust and useful in all populations.

Keywords::

• biological age
• GrimAge
• PhenoAge
• phenotypic age
• smoking

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2020-0333

H T Cronjé, M Pieters, C Nienaber-Rousseau and H R Elliott conceptualized the study. Funding was acquired by M Pieters and F R Green. H T Cronjé performed the data analysis and wrote the manuscript. M Pieters supervised the data analysis and interpreted the results with J L Min, H R Elliott and H T Cronjé. All authors contributed to the critical review and editing of the manuscript.

Acknowledgments

The authors thank all those who participated in the PURE-SA-NW study and those who made the PURE-SA-NW study possible, including the fieldworkers, researchers and staff of both PURE-SA-NW (Africa Unit for Transdisciplinary Health Research, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa) and PURE International (S Yusuf and the PURE project office staff at the Population Health Research Institute, Hamilton Health Sciences and McMaster University, Ontario, Canada) teams. The authors also thank the staff of Bristol Bioresource Laboratories (Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK), who generated the DNA methylation data.

Financial & competing interests disclosure

The PURE-SA-NW study was funded by North-West University, South African National Research Foundation, Population Health Research Institute, South African Medical Research Council, North West Province Health Department and South African Netherlands Partnerships in Development. Grants from the South African National Research Foundation, Academy of Medical Sciences UK (Newton Fund Advanced Fellowship Grant [AMS-NAF1-Pieters to M Pieters and F R Green]) and South African Medical Research Council funded the DNA methylation analysis. H T Cronjé was supported by the South African National Research Foundation (SFH106264, MND121094) and is currently supported by the Novo Nordisk Fonden Challenge Programme: Harnessing the Power of Big Data to Address the Societal Challenge of Aging (NNF17OC0027812). H R Elliott works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council and the University of Bristol (MC_UU_00011/5). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Ethical approval for the 2015 data collection of the PURE-SA-NW study was granted by the Health Research Ethics Committee of North-West University (NWU-00016-10-A1, NWU-00119-17-A1). All participants provided written informed consent, including consent for genetic/epigenetic analysis.

Data sharing statement

The data that support the findings of this study are available upon reasonable request and with the permission of the Health Research Ethics Committee of North-West University and the principal investigator of the PURE-SA-NW study, I M Kruger ([email protected]), at North-West University’s Africa Unit for Transdisciplinary Health Research.

Additional information

Funding

The PURE-SA-NW study was funded by North-West University, South African National Research Foundation, Population Health Research Institute, South African Medical Research Council, North West Province Health Department and South African Netherlands Partnerships in Development. Grants from the South African National Research Foundation, Academy of Medical Sciences UK (Newton Fund Advanced Fellowship Grant [AMS-NAF1-Pieters to M Pieters and F R Green]) and South African Medical Research Council funded the DNA methylation analysis. H T Cronjé was supported by the South African National Research Foundation (SFH106264, MND121094) and is currently supported by the Novo Nordisk Fonden Challenge Programme: Harnessing the Power of Big Data to Address the Societal Challenge of Aging (NNF17OC0027812). H R Elliott works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council and the University of Bristol (MC_UU_00011/5). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.