Summary: A new study has found that aging clocks, which gauge biological age, do so by measuring stochastic changes in cellular processes, particularly in DNA methylation. These clocks indicate that biological age, influenced by lifestyle and environmental factors, can deviate significantly from chronological age.
The study reveals that these variations increase with age, reflecting a loss of cellular control over time. Importantly, interventions such as calorie restriction or cellular reprogramming can influence these stochastic variations, suggesting potential avenues for interventions related to aging and cellular rejuvenation.
Highlights:
- Mechanism of aging clocks: Aging clocks measure biological age by tracking the accumulation of random changes in DNA methylation, a process that naturally diverges as we age.
- Influence of lifestyle on aging: Lifestyle factors, such as smoking, can accelerate stochastic changes, while interventions such as reducing caloric intake can decrease these changes.
- Reversibility of aging: Reprogramming adult cells into stem cells can reverse the strong stochastic variations associated with older cells back to the low levels typical of young, healthy cells.
Source: University of Cologne
Aging clocks can measure the biological age of humans with high precision. Biological age can be influenced by environmental factors such as smoking or diet, thus deviating from chronological age calculated from the date of birth.
The precision of these aging clocks suggests that the aging process follows a schedule. Scientists David Meyer and Professor Björn Schumacher from CECAD, the Center of Excellence for Cellular Stress Responses in Aging-Associated Diseases at the University of Cologne, have discovered that aging clocks actually measure the increase in stochastic changes in cells.
The study “Aging clocks based on accumulating stochastic variation” was published in Natural aging.
“Aging is triggered when the building blocks of our cells are damaged. Where this damage occurs is largely random. Our work combines the precision of aging clocks with the accumulation of fully stochastic changes in our cells,” said Professor Schumacher.
Fewer controls, more noise
As we age, control of the processes that occur in our cells becomes less effective, leading to more stochastic results. This is particularly evident in the accumulation of stochastic changes in DNA methylation. Methylation refers to chemical changes that affect DNA, the building blocks of the genome.
These methylation processes are strictly regulated within the body. However, over the course of life, random changes occur in methylation patterns. The accumulation of variations is a very accurate indicator of a person’s age.
The loss of control over cells and increased stochastic variation is not limited to DNA methylation. Meyer and Schumacher demonstrate that increasing stochastic variations also in gene activity can be used as an aging clock.
“In principle, it would be possible to go even further, allowing stochastic variations in any cellular process to predict age,” Schumacher said.
According to the authors, it is above all crucial to check whether such aging clocks can show the success of interventions that slow down the aging process or harmful factors that accelerate aging.
Using available datasets, scientists showed that smoking increases random changes in humans and that “anti-aging” interventions, such as lower calorie intake in mice, reduce variation in patterns of methylation.
They also showed that stochastic noise is even reversible through the reprogramming of body cells into stem cells. The scientists compared human skin fibroblasts that have been reprogrammed into stem cells and, thanks to the reprogramming, are rejuvenating.
The strong variation indicative of the age of the body’s cells has in fact reversed itself into a weak stochastic noise of young stem cells.
Meyer and Schumacher hope that their findings on loss of regulation and the accumulation of stochastic variation will lead to new interventions that can address the root cause of aging and could even lead to cellular rejuvenation.
A goal of such interventions could be the repair of stochastic DNA changes or better control of gene expression.
About this research news in genetics and aging
Author: Anna Euteneuer
Source: University of Cologne
Contact: Anna Euteneuer – University of Cologne
Picture: Image is credited to Neuroscience News
Original research: Free access.
“Aging clocks based on the accumulation of stochastic variations” by Björn Schumacher et al. Natural aging
Abstract
Aging clocks based on the accumulation of stochastic variations
Aging clocks have constituted one of the most important recent breakthroughs in the biology of aging and can provide indicators of the effectiveness of interventions in the aging process and preventive treatments for age-related diseases.
The reproducibility of precise aging clocks has reignited the debate over whether a programmed process causes aging.
We show here that the accumulation of stochastic variations in purely simulated data is sufficient to construct aging clocks, and that first- and second-generation aging clocks are consistent with the accumulation of stochastic variations in methylation. DNA or transcriptomic data.
We find that the accumulation of stochastic variation is sufficient to predict chronological and biological age, indicated by significant prediction differences in smoking, calorie restriction, heterochronic parabiosis, and partial reprogramming.
Although our simulations do not explicitly rule out a programmed aging process, our results suggest that the stochastic accumulation of changes in any dataset having a ground state at age zero is sufficient to generate aging clocks.
News Source : neurosciencenews.com
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