We discovered a subtle genetic imbalance that could drive aging : ScienceAlert

Scientists have found an extremely subtle twist in the genetics of aging cells that seems to make them less and less functional as time goes on.

R.Researchers at Northwestern University have revealed Animals such as mice, rats, killifish, and even humans show a gradual imbalance of long and short genes in virtually every cell in their body as they age.

The discovery suggests that there are no specific genes that control the aging process. Instead, old age appears to be governed by systems-level changes with complex effects. And this can affect thousands of different genes and their respective proteins.

However, for an individual gene, the changes are so small as to be insignificant. That is probably why they have gone under the radar until now.

“We have mainly focused on a small number of genes, thinking that a few genes would explain the disease.” He says Northwestern University data scientist Luis Amaral.

“So maybe we didn’t focus on the right thing before. Now that we have this new understanding, it’s like having a new instrument. It’s like Galileo with a telescope, looking into space. Looking at gene activity through this new lens will allow us to see biological phenomena differently”.

Normally, in an individual cell or a group of cells, a code represented in DNA is translated into RNA, becoming a collection of free-floating instructions known as transcriptome.

This mobile library of genetic recipes is what the cell uses to create its parts and carry out its various functions. Its content also seems to change with age.

In a healthy young animal, the activity of short and long genes is balanced in a transcriptome, and this balance is carefully controlled and maintained. But as an individual ages, short genes become more of a mainstream trend.

In several different types of animals, in fact, shorter transcriptomes were found to proliferate with age.

“Changes in gene activity are very, very small, and these small changes involve thousands of genes.” Explain developmental biologist Thomas Stoeger.

“We found that this change was constant in different tissues and in different animals. We found it almost everywhere. I find it very elegant that a single, relatively concise principle seems to explain almost all changes in gene activity that occur in animals. as they get older.”

Like the aging process itself, the transition to smaller transcriptomes begins early and is gradual.

In rats, tissue samples taken at 4 months of age had a relatively longer median gene length than those taken at 9 months of age.

The transcriptome changes found in killifish from the age of 5 weeks to 39 weeks were similar.

To test the pattern in humans, the researchers turned to data from the Genotype-Tissue Expression (GTEx), which publicly provides genetic information collected from nearly 1,000 deceased individuals.

Among humans, transcriptome length was once again found to predict old age, becoming significant in the 50-69 age group.

Compared to the younger age group of 30-49 years, the older age group showed longer transcripts that were less likely to “bend” or become functionally active compared to the shorter ones.

“The result for humans is very strong because we have more samples from humans than from other animals.” He says Amaral.

“It was also interesting because all the mice we studied are genetically identical, the same sex, and raised in the same laboratory conditions, but humans are all different. They all died of different causes and at different ages. We analyzed samples from men and women for separated and found the same pattern.

Still not satisfied with their results, Northwestern researchers next investigated the effect of various anti-aging treatments. interventions on the length of the transcriptomes. Most of the interventions favored long transcripts, despite their different impacts on the body.

The authors conclude that aging cannot be reduced to a single source of transcriptome imbalance.

Instead they argue that “multiple environmental and internal conditions” likely lead to short genes becoming more active in the body.

“Encouraged by our findings on antiaging interventions, we believe that understanding the direction of causality between other age-dependent cellular and transcriptomic changes and length-associated transcriptome imbalance could open new research directions for antiaging interventions,” they conclude. the authors. conclude.

The study was published in Nature Aging.