Summary: A fresh research has uncovered a direct connection between bodily mutations and genetic modifications, challenging established sights on aging. Researchers found that strange genetic mutations drive repetitive changes in DNA imprinting, offering fresh insights into the partnership between gene accumulation and genetic clocks.
This suggests that genomic changes may trail, rather than reason, aging, making it harder to change aging than originally thought. These results redefine our knowledge of aging at the chemical level and keep important implications for future anti-aging treatments.
Important Information:
- Mutation-Epigenetic Link: Random genetic variants drive repetitive genetic changes.
- Aging Complexity: Epigenetic watches perhaps record aging caused by physiological abnormalities.
- Medical Impact: Reversing aging does require addressing abnormalities, not only epigenetics.
Origin: UCSD
Analysts at University of California San Diego School of Medicine have published findings that shed new light on an old question: what causes aging at the molecular degree?
Their results, published in Nature Aging, define a never-before-seen link between the two most approved theories: strange genetic mutations and predictable genetic modifications.
The former, also known as the genetic clock concept, has been extensively used by scientists as a steady, quantitative measure of natural aging.
But, the new research suggests that the procedure may not be so easy.
“Major research institutions and companies are betting on turning back the genetic time as a strategy to change the effects of aging, but our study suggests that this may just be treating a sign of aging, not the underlying cause, ” said co-corresponding artist Trey Ideker, Ph. D. , a teacher at UC San Diego School of Medicine and UC San Diego Jacobs School of Engineering.
“If variants are in fact responsible for the observed genetic modifications, this point could ultimately change the way we approach anti-aging efforts in the future. ”
There are two dominating theories about the connection between aging and DNA. The somatic gene theory suggests that aging is caused by the formation of variants, permanent changes in our DNA collection that occur sporadically.
The genetic clock theory suggests that aging occurs due to the accumulation of genetic modifications, small changes to the chemical structure of DNA that do not change the actual sequence, but otherwise change which genes are on or off. Unlike abnormalities, genetic changes can also be reversed in some cases.
Because genetic changes only occur at specific sites on our chromosome rather than at obscure locations, they are easier to calculate and have become a go-to method for scientists to determine the “biological age” of cells.
However, scientists have long wondered about the source of these epigenetic changes.
To answer this fundamental question, researchers analyzed data from 9,331 patients catalogued in the Cancer Genome Atlas and the Pan-Cancer Analysis of Whole Genomes.
By comparing genetic mutations to epigenetic modifications, they found that mutations were predictably correlated with changes in DNA methylation, one type of epigenetic modification.
They found that a single mutation could cause a cascade of epigenetic changes across the genome, not just where the mutation occurred. Using this relationship, the researchers were able to make similar predictions of age using either mutations or epigenetic changes.
“Epigenetic clocks have been around for years, but we’re only now beginning to answer the question of why epigenetic clocks tick in the first place, ” said first author Zane Koch, a Ph. D. candidate in bioinformatics at UC San Diego.
“Our study demonstrates for the first time that epigenetic changes are intricately and predictably tied to random genetic mutations. ”
The study ’s authors note that further research is needed to fully understand the relationship between somatic mutations and epigenetic changes in aging.
However, the study ’s findings provide a major breakthrough in our understanding of the aging process and have important implications for the development of new therapies aimed at preventing or reversing aging.
“If somatic mutations are the fundamental driver of aging and epigenetic changes simply track this process, it ’s going to be a lot harder to reverse aging than we previously thought, ” added co-corresponding author Steven Cummings, M. D. , executive director of the San Francisco Coordinating Center at UC San Francisco and senior research scientist at Sutter Health’s California Pacific Medical Center Research Institute.
“This shifts our focus from viewing aging as a programmed process to one that ’s largely influenced by random, cumulative changes over time. ”
In addition to Ideker, Cummings and Koch, the study was co-authored by Adam Li at UC San Diego and Daniel S. Evans at California Pacific Medical Center Research Institute and UC San Francisco.
Funding: This study was funded by the National Institutes of Health ( grants U54 CA274502 and P41 GM103504 ).
About this genetics and aging research news
Author: Miles Martin
Source: UCSD
Contact: Miles Martin – UCSD
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Somatic mutation as an explanation for epigenetic aging ” by Trey Ideker et al. Nature Aging
Abstract
Somatic mutation as an explanation for epigenetic aging
DNA methylation marks have recently been used to build models known as epigenetic clocks, which predict calendar age.
As methylation of cytosine promotes C-to-T mutations, we hypothesized that the methylation changes observed with age should reflect the accrual of somatic mutations, and the two should yield analogous aging estimates.
In an analysis of multimodal data from 9,331 human individuals, we found that CpG mutations indeed coincide with changes in methylation, not only at the mutated site but with pervasive remodeling of the methylome out to ±10 kilobases.
This one-to-many mapping allows mutation-based predictions of age that agree with epigenetic clocks, including which individuals are aging more rapidly or slowly than expected. Moreover, genomic loci where mutations accumulate with age also tend to have methylation patterns that are especially predictive of age.
These results suggest a close coupling between the accumulation of sporadic somatic mutations and the widespread changes in methylation observed over the course of life.
