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Longitudinal changes in the genetic and environmental influences on the epigenetic clocks across old age: Evidence from two twin cohorts.
EBioMedicine. 2019 Feb;40:710-716. doi: 10.1016/j.ebiom.2019.01.040
Jylhävä J, Hjelmborg J, Soerensen M, Munoz E, Tan Q, Kuja-Halkola R, Mengel-From J, Christensen K, Christiansen L, Hägg S, Pedersen NL, Reynolds CA
Abstract:
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.
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.
PMID: 30704927
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413471/