Longitudinal changes in the genetic and environmental influences on the epigenetic clocks across old age: Evidence from two twin cohortsResearch in context
Juulia Jylhävä,
Jacob Hjelmborg,
Mette Soerensen,
Elizabeth Munoz,
Qihua Tan,
Ralf Kuja-Halkola,
Jonas Mengel-From,
Kaare Christensen,
Lene Christiansen,
Sara Hägg,
Nancy L. Pedersen,
Chandra A. Reynolds
Affiliations
Juulia Jylhävä
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Corresponding author.
Jacob Hjelmborg
The Danish Twin registry and the Danish Aging Research Center at Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark
Mette Soerensen
The Danish Twin registry and the Danish Aging Research Center at Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark
Elizabeth Munoz
Department of Psychology, The University of California at Riverside, California, USA
Qihua Tan
The Danish Twin registry and the Danish Aging Research Center at Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark; Unit of Human Genetics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
Ralf Kuja-Halkola
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Jonas Mengel-From
The Danish Twin registry and the Danish Aging Research Center at Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark
Kaare Christensen
The Danish Twin registry and the Danish Aging Research Center at Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark
Lene Christiansen
The Danish Twin registry and the Danish Aging Research Center at Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark; Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Sara Hägg
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Nancy L. Pedersen
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Chandra A. Reynolds
Department of Psychology, The University of California at Riverside, California, USA
Background: Measures based on DNA methylation, epigenetic clocks, have recently gained attraction as predictors of mortality and age-related pathologies. However, the origins of variation in these measures are not well understood. Methods: In a pooled sample of 104 Swedish and Danish twin pairs, we estimated, at the mean age of 70 (baseline) and 79 years (follow-up), the genetic and environmental influences on the Horvath and Levine clocks. Findings: A model incorporating additive genetic (A) and person-specific environmental (E) influences best explained the variation in both clocks. Heritability was estimated at 55% at baseline and at 51% at follow-up for the Horvath clock and 34% at baseline and 41% at follow-up for the Levine clock. For the Horvath clock, new sources of A influences emerged at follow-up, whereas for the Levine clock, the same A influences accounted for the genetic variance at both measurement occasions. The cross-time phenotypic correlations, 0·52 for the Horvath clock and 0·36 for the Levine clock, were mediated primarily by genetic factors, whereas the person-specific environmental factors were completely different at the two measurement occasions. Interpretation: For both clocks, new sources of person-specific environmental influences emerge with age. The epigenetic clocks might thus be responsive to new environmental stimuli even at old age. Fund: NIH (R01;AG04563;AG10175;AG028555) the MacArthur Foundation Research Network on Successful Aging, FAS/FORTE (97:0147:1B;2009-0795), Swedish Research Council (825-2007-7460;825-2009-6141;521-2013-8689;2015-03255;2015-06796;2018-02077), FORTE (2013-2292), the Strategic Research Program in Epidemiology at KI, VELUX FOUNDATION, NIA (P01-AG08761), the EU (FP7/2007-2011;259679) and The Danish National Program for Research Infrastructure 2007 (9-063256). Keywords: Epigenetic clock, DNA methylation, Aging, Heritability, Sources of variation
