scholarly journals A decade of epigenetic change in aging twins: genetic and environmental contributions to longitudinal DNA methylation

2019 ◽  
Author(s):  
Chandra A. Reynolds ◽  
Qihua Tan ◽  
Elizabeth Munoz ◽  
Juulia Jylhävä ◽  
Jacob Hjelmborg ◽  
...  

Summary/AbstractBackgroundEpigenetic changes may result from the interplay of environmental exposures and genetic influences and contribute to differences in age-related disease, disability and mortality risk. However, the etiologies contributing to stability and change in DNA methylation have rarely been examined longitudinally.MethodsWe considered DNA methylation in whole blood leukocyte DNA across a 10-year span in two samples of same-sex aging twins: (a) Swedish Adoption Twin Study of Aging (SATSA; N = 53 pairs, 53% female; 62.9 and 72.5 years, SD=7.2 years); (b) Longitudinal Study of Aging Danish Twins (LSADT; N = 43 pairs, 72% female, 76.2 and 86.1 years, SD=1.8 years). Joint biometrical analyses were conducted on 358,836 methylation probes in common. Bivariate twin models were fitted, adjusting for age, sex and country.ResultsOverall, results suggest genetic contributions to DNA methylation across 358,836 sites tended to be small and lessen across 10 years (broad heritability M=23.8% and 18.0%) but contributed to stability across time while person-specific factors explained emergent influences across the decade. Aging-specific sites identified from prior EWAS and methylation age clocks were more heritable than background sites. The 5,037 sites that showed the greatest heritable/familial-environmental influences (p<1E-07) were enriched for immune and inflammation pathways while 2,020 low stability sites showed enrichment in stress-related pathways.ConclusionsAcross time, stability in methylation is primarily due to genetic contributions, while novel experiences and exposures contribute to methylation differences. Elevated genetic contributions at age-related methylation sites suggest that adaptions to aging and senescence may be differentially impacted by genetic background.

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120388 ◽  
Author(s):  
Fu-Hui Xiao ◽  
Yong-Han He ◽  
Qi-Gang Li ◽  
Huan Wu ◽  
Long-Hai Luo ◽  
...  

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S32-S33
Author(s):  
Morgan E Levine ◽  
Sara Hagg

Abstract Epigenetic changes are one of the Hallmarks of Aging. DNA methylation is a key epigenetic mark that has been shown to change during aging. Several "clocks" have been developed whereby changes in DNA methylation can be used to predict chronological, and perhaps, biological age. This symposium will focus on recent advances in understanding how and why changes in DNA methylation occur during aging and whether these changes play a causal role in age-related functional declines and disease.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hua Ren ◽  
Veronica Collins ◽  
Sandy J. Clarke ◽  
Jin-Song Han ◽  
Paul Lam ◽  
...  

Tai chi exercise has been shown to improve physiological and psychosocial functions, well-being, quality of life, and disease conditions. The biological mechanisms by which tai chi exerts its holistic effects remain unknown. We investigated whether tai chi practice results in positive epigenetic changes at the molecular level.Design. The DNA methylation profiles of sixty CpG-dinucleotide marks in female tai chi practitioners (N=237; 45–88 years old) who have been practising tai chi for three or more years were compared with those of age-matched control females (N=263) who have never practised tai chi.Results. Six CpG marks originating from three different chromosomes reveal a significant difference (P<0.05) between the two cohorts. Four marks show losses while two marks show gains in DNA methylation with age in the controls. In the tai chi cohort all six marks demonstrate significant slowing (by 5–70%) of the age-related methylation losses or gains observed in the controls, suggesting that tai chi practice may be associated with measurable beneficial epigenetic changes.Conclusions. The results implicate the potential use of DNA methylation as an epigenetic biomarker to better understand the biological mechanisms and the health and therapeutic efficacies of tai chi.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara Zocher ◽  
Rupert W. Overall ◽  
Mathias Lesche ◽  
Andreas Dahl ◽  
Gerd Kempermann

AbstractThe decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Lifestyle interventions can improve brain function during aging, but their influence on age-related epigenetic changes is unknown. Using genome-wide DNA methylation sequencing, we here show that experiencing a stimulus-rich environment counteracts age-related DNA methylation changes in the hippocampal dentate gyrus of mice. Specifically, environmental enrichment prevented the aging-induced CpG hypomethylation at target sites of the methyl-CpG-binding protein Mecp2, which is critical to neuronal function. The genes at which environmental enrichment counteracted aging effects have described roles in neuronal plasticity, neuronal cell communication and adult hippocampal neurogenesis and are dysregulated with age-related cognitive decline in the human brain. Our results highlight the stimulating effects of environmental enrichment on hippocampal plasticity at the level of DNA methylation and give molecular insights into the specific aspects of brain aging that can be counteracted by lifestyle interventions.


2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Amy E. Morgan ◽  
Katie D. Acutt ◽  
Mark T. Mc Auley

Abstract There is a growing need for biomarkers which predict age-onset pathology. Although this is challenging, the methylome offers significant potential. Cancer is associated with the hypermethylation of many gene promoters, among which are developmental genes. Evolutionary theory suggests developmental genes arbitrate early-late life trade-offs, causing epimutations that increase disease vulnerability. Such genes could predict age-related disease. The aim of this work was to optimise an electrochemical procedure for the future investigation of a broad range of ageing-related pathologies. An electrochemical approach, which adopted three analytical techniques, was used to investigate DNA methylation in the engrailed-1 (EN1) gene promoter. Using synthetic single-stranded DNA, one technique was able to detect DNA at concentrations as low as 10 nM, with methylation status distinguishable at concentrations &gt;25 nM. A negative correlation could be observed between % methylation of a heterogeneous solution and the key electrochemical parameter, charge transfer resistance (Rct; r = −0.982, P&lt;0.01). The technique was applied to the breast cancer cell line Michigan Cancer Foundation-7 (MCF-7), where a similar correlation was observed (r = −0.965, P&lt;0.01). These results suggest electrochemistry can effectively measure DNA methylation at low concentrations of DNA. This has implications for the future detection of age-related disease.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gerald S. Wilkinson ◽  
Danielle M. Adams ◽  
Amin Haghani ◽  
Ake T. Lu ◽  
Joseph Zoller ◽  
...  

AbstractExceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.


2011 ◽  
Vol 71 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Lara K. Park ◽  
Simonetta Friso ◽  
Sang-Woon Choi

Nutritional epigenetics has emerged as a novel mechanism underlying gene–diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modulates gene expression without changes in the underlying bp sequence, ultimately determining phenotype from genotype. DNA methylation and post-translational histone modifications are classical levels of epigenetic regulation. Epigenetic phenomena are critical from embryonic development through the aging process, with aberrations in epigenetic patterns emerging as aetiological mechanisms in many age-related diseases such as cancer, CVD and neurodegenerative disorders. Nutrients can act as the source of epigenetic modifications and can regulate the placement of these modifications. Nutrients involved in one-carbon metabolism, namely folate, vitamin B12, vitamin B6, riboflavin, methionine, choline and betaine, are involved in DNA methylation by regulating levels of the universal methyl donor S-adenosylmethionine and methyltransferase inhibitor S-adenosylhomocysteine. Other nutrients and bioactive food components such as retinoic acid, resveratrol, curcumin, sulforaphane and tea polyphenols can modulate epigenetic patterns by altering the levels of S-adenosylmethionine and S-adenosylhomocysteine or directing the enzymes that catalyse DNA methylation and histone modifications. Aging and age-related diseases are associated with profound changes in epigenetic patterns, though it is not yet known whether these changes are programmatic or stochastic in nature. Future work in this field seeks to characterise the epigenetic pattern of healthy aging to ultimately identify nutritional measures to achieve this pattern.


Author(s):  
Gerald S. Wilkinson ◽  
Danielle M. Adams ◽  
Amin Haghani ◽  
Ake T. Lu ◽  
Joseph Zoller ◽  
...  

AbstractExceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.


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