Study explains how epigenetic factors relate to aging

According to a study, headed by a psychologist at the University of California, Riverside, genetic background may influence how people adapt to aging in late life.

Chandra Reynolds. Image Credit: University of California, Riverside.

Published in the Aging Cell journal, the study has implications for how aging is associated with epigenetic factors.

Epigenesis can be defined as a process where chemicals adhered to DNA regulate its activity. Epigenetic modifications can be passed on to offspring, and may be crucial to the accelerated aging process and reduced physical and cognitive functions that usually accompany aging.

Epigenetic changes that lead to altered gene expression could be caused by several biological processes, including DNA methylation, which is being studied by one of the researchers.

Methyl groups are introduced to the DNA molecule in DNA methylation. There are four different kinds of nucleotides in DNA—that is, A, G, T, and C nucleotides. DNA methylation takes place at the C bases of eukaryotic DNA. Modifications in DNA methylation strongly correlate with the aging process.

Over a span of 10 years, Chandra Reynolds, a professor of psychology at the University of California, Riverside, and her collaborators had examined DNA methylation in 96 pairs of same-sex aging Danish and Swedish twins—the first longitudinal twin analysis to determine the extent to which environmental and genetic effects play a role in site-specific DNA methylation across time.

The researchers noted that individual variations in blood DNA methylation—quantified at over 350,000 locations in the aging twins over the epigenome—are partially heritable in late life and longitudinally over 10 years—aged 69 to 79.

These results can provide a deeper understanding of the environmental and genetic influences that contribute to the dynamics and stability of methylation in the aging process and establish a framework for forthcoming work in varied populations.

We also found methylation sites previously associated with age and included in methylation ‘clocks’ are more heritable than the other remaining sites. The sites evidencing the greatest heritability reside in genes that participate in immune-inflammatory as well as neurotransmitter pathways. Sites that show less stability in methylation across 10 years reside in genes that participate in stress-related pathways.”

Chandra Reynolds, Study Corresponding Author and Professor, Department of Psychology, University of California, Riverside

Reynolds, a specialist in cognitive aging, headed the study.

The fact that age-related locations are among the most heritable indeed supports the genetic regulation of the rates of biological aging, such as regulation of how well individuals react to environmental challenges, for example, exposures to viruses like SARS-Cov-2 that is responsible for causing the COVID-19 pandemic.

Altered methylation patterns have been observed with aging, and as methylation differences may result in part from our experiences and behavior, they may be modifiable. Our results highlight that even in late life, amid the ‘slings and arrows of outrageous fortune,’ some of the individual differences in methylation are moderately heritable and contribute to methylation patterns 10 years later.”

Chandra Reynolds, Study Corresponding Author and Professor, Department of Psychology, University of California, Riverside

According to Reynolds, while genetic effects contribute to stability, non-shared factors accumulate in significance with age, indicating an increasing diversity of how individuals react o environmental exposures. Generally, heritability is attributed to stable genetic contributions, added Reynolds, however with a growing role of non-shared environmental factors—those exclusive to an individual and not shared with siblings—across age.

Reynolds further added that sites of DNA methylation associated with aging are generally more heritable. This is consistent with the genetic regulation of the rates of biological aging, maybe including genetic sites that play a role in neurotransmitter pathways and immune-inflammatory pathways, and described how individuals adapt to aging and health conditions.

The most heritable sites may participate in these pathways, which suggests that adaptions to aging and senescence may be differentially impacted by genetic background. That the most heritable or familial sites lie within genes that participate in immune-inflammatory pathways suggests that how we adapt to aging processes, including resistance to—or challenges from—illness, may be partly genetically regulated.”

Chandra Reynolds, Study Corresponding Author and Professor, Department of Psychology, University of California, Riverside