Longitudinal studies provide a valuable approach to understanding the genetic and environmental contributions to the stability and change in DNA methylation over time. Some recent studies link biological aging to lifestyle factors.
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In this article:
- Epigenetic Markers to Read Biological Age
- A Longitudinal Study of Twins in Epigenetic Research
- Genetic and Environmental Contributions
DNA Methylation Effects on Biological Age
- Cytosine methylation in vertebrates occurs mainly at the CG dinucleotide sequences [4].
- CpG sites in mammals are hotspots for mutation, where upwards of 70% of cytosines are methylated [2].
Human DNA has a high level of methylation. Uncovering if epigenetic changes can result from the interplay of environmental and genetic influences can contribute to:
- Development of complex diseases
- Accelerated aging
- Decline in cognitive and physical function with age
Using identical twins provides an epigenome-wide association in linking environmental exposure to differential epigenetic regulation [5].
Epigenetic Markers to Read Biological Age
It has been observed that individuals with the same chronological age can differ from their biological age. Little is known about what controls our biological clocks. Currently, DNA methylation is the most promising molecular marker for monitoring aging [1].
Measurable gene-environment associations are possible because markers have been utilized to track differences in biological aging amongst individuals. Analysis of epigenetic rates of aging will help find associations between our biological clocks and lifestyle [3].
A Longitudinal Study of Twins in Epigenetic Research
The case for using identical twins is their shared genetic make-up and rearing environment make them ideal for confounding factors in human disease and mortality. Twin studies are extremely valuable for interpreting the genetic and environmental basis of epigenetics.
Co-twin design uses identical twin’s differences to uncover the link between complex diseases and environmental exposure. The comparison of identical twins reveals the acceleration of epigenetic changes over time [6].
The figure represents the identical DNA sequence in twin pairs, with one methylation site occurring in the diseased twin depicted in red. The differences in twin’s DNA methylation can find links between epigenetic variation and environmental factors.
The use of multiple twin pairs shows where different methylation sites occur and help estimate the genetic and environmental contributions to health conditions such as biological aging, disease, and mortality [6].
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Genetic and Environmental Contributions
Stability in late-life methylation is due to genetic contributions, while novel experiences and exposures contribute to methylation differences [5]. Genetic contributions at age-related methylation sites suggest that adaptations to aging are impacted by an individual’s unique genetic background [5].
Low stability CpG sites had greater variability in gene expression over time due to nonshared factors between the twin pairs. This suggests that these sites are responsive to “new” environmental cues, even at old age [5].
Heritable factors may be associated with differential immune responses amongst individuals. Some individuals are better adapted to the aging process than others due to the genetic influences that separate individuals from one another [5].
There is mounting evidence supporting that a certain gene’s status can affect a disease’s immune evasion capabilities. The most heritable sites within DNA participate in immune and inflammation pathways. This suggests that adaptations to aging are impacted by one’s genetic background [5].
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