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Aging may be driven by genetic imbalances

By using artificial intelligence to analyze data from a wide variety of tissues – collected from humans, mice, rats, and killifish – a team of researchers from Northwestern University has discovered a previously unknown mechanism that drives aging processes. The experts found that the length of genes can explain most changes at the molecular level that occur during aging. 

More specifically, longer genes – which have more nucleotides that translate to amino acids subsequently forming larger proteins – were linked to longer lifespans, while a larger abundance of shorter genes was associated to shorter lifespans. Thus, the process of aging seems to be related to a shift in activity toward shorter genes that causes gene activity in cells to become unbalanced.

The scientists were surprised to find that this phenomenon was nearly universal, spanning several animal species – including humans – and a large variety of tissues from blood, muscle, bones, and organs such as the liver, the heart, the intestines, the brain, and the lungs.

“The changes in the activity of genes are very, very small, and these small changes involve thousands of genes,” said study lead author Thomas Stoeger, an expert in Chemical and Biological Engineering at Northwestern. “We found this change was consistent across different tissues and in different animals. We found it almost everywhere. I find it very elegant that a single, relatively concise principle seems to account for nearly all of the changes in activity of genes that happen in animals as they age.”

“The imbalance of genes causes aging because cells and organisms work to remain balanced — what physicians denote as homeostasis,” added senior author Luís A.N. Amaral, a professor of Chemical and Biological Engineering at the same university. 

“Imagine a waiter carrying a big tray. That tray needs to have everything balanced. If the tray is not balanced, then the waiter needs to put in extra effort to fight the imbalance. If the balance in the activity of short and long genes shifts in an organism, the same thing happens. It’s like aging is this subtle imbalance, away from equilibrium. Small changes in genes do not seem like a big deal, but these subtle changes are bearing down on you, requiring more effort.”

Surprisingly, the researchers found that shorter genes could also play important roles in our bodies, such as, for instance, in fighting against pathogens. “Some short genes could have a short-term advantage on survival at the expense of ultimate lifespan. Thus, outside of a research laboratory, these short genes might help survival under harsh conditions at the expense of shortening the animal’s ultimate lifespan,” Stoeger explained.

These findings could open new pathways for the development of therapeutics that could slow or even reverse aging, by re-balancing our genes and trying to expand, through biological engineering, the lifespan of longer genes. However, further research on these complex genetic processes, together with the development of more advanced technological tools, are needed to achieve these aims.

The study is published in the journal Nature Aging.


By Andrei Ionescu, Staff Writer

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