We've Discovered A Subtle Genetic Imbalance That May Drive Aging

Scientists have discovered a subtle twist in the genetics of aging cells that makes them less functional as time goes on.

Animals like mice, rats, killifish, and even humans show a gradual balance of long and short genes in their bodies as they age.

There aren't specific genes that control aging, according to the discovery. Old age seems to be governed by systems level changes. Thousands of genes can be impacted by this.

The changes are so small that they are not significant. That's probably why they didn't tell us until now.

The focus has been on a small number of genes, thinking that a few genes would explain disease.

Maybe we didn't focus on the right thing before. It's like getting a new instrument. Galileo used a telescope to look at space. Through this new lens, we will be able to see biological phenomena in a different way.

A transcriptome is a collection of free-floating instructions that can be found in any cell.

The cell uses a mobile library of genetic recipes to make its parts. It seems like its contents change with age.

The activity of short and long genes is balanced in a healthy animal. Short genes become more of a trend as an individual ages.

Short transcriptomes were found to grow with age in a number of different animals.

Thousands of genes are involved in the small changes in the activity of genes.

There was a consistent change in different tissues. We found it all over the place. A single principle seems to account for nearly all of the changes in activity of genes that happen in animals as they get older.

The transition to smaller transcriptomes is gradual and begins early.

Tissue samples taken at 4 months of age had a longer median length of genes than those taken at 9 months of age.

The transcriptome changes in killifish were the same as in other fish.

The data from the Genotype-Tissue Expression project was used to test the pattern in humans.

The 50 to 69 age group was where transcriptome length became significant.

Longer transcripts were less likely to fold or become functionally active compared to shorter transcripts in the older age group.

The result for humans is very strong because we have a lot of samples for humans.

All the mice we studied are genetically identical, the same gender, and raised in the same lab conditions, but the humans are different. All of them died from different causes. The same pattern was found by analyzing samples from both men and women.

The effect of several anti-aging interventions on the length of transcriptomes was investigated. Long transcripts were favored by the majority of interventions.

Aging can't be boiled down to a single origin of transcriptome imbalance.

They argue that short genes become more active in the body because of multiple environmental and internal conditions.

"Spurred by our findings on anti-aging interventions, we believe that understanding the direction of causality between other age- dependent cellular and transcriptomic changes and length- associated transcriptome imbalance could open novel research directions for anti-aging interventions," the authors conclude.

The study was published in a journal.