Scientists unravel the mystery of aging: gene length is the deciding factor

Scientists believe they have discovered the secret of aging.

A major genetic analysis of people, rodents and fish found that the length of their DNA was directly related to their biological age.

Shorter genes were associated with a shorter lifespan, while longer genes were linked to better health and longevity.

Scientists believe that if they can hijack this mechanism, it could pave the way for a source of youthful drugs that could slow, or even reverse, aging.

Dr. Thomas Stoeger, lead author of the study at Northwestern University in Illinois, said: “I find it very elegant that a single, relatively concise principle seems to explain almost all the changes in gene activity that occur in the animals as they age.’

The length of a gene is based on the number of nucleotides in it. Each nucleotide chain is translated into an amino acid, forming a protein.

Therefore, a very long gene produces a large protein, and a short gene produces a small protein. A cell needs to have a balanced number of small and large proteins to achieve homeostasis, and problems occur when this balance is thrown off.

In the study, researchers examined genetic data from several large datasets, including the Genotype-Tissue Expression Project, a tissue bank funded by the National Institutes of Health that archives samples from human donors for the purpose of research

The research team first analyzed tissue samples from mice, rats and killifish of various ages.

In all the animals, the researchers noticed subtle changes in thousands of different genes across the samples.

This means that not only a small subset of genes contribute to aging. Aging, on the other hand, is characterized by changes at the systems level.

This view differs from prevailing biological approaches that study the effects of single genes.

Since the emergence of modern genetics in the early 20th century, many researchers hoped to be able to attribute many complex biological phenomena to single genes.

And although some diseases, such as hemophilia, result from single gene mutations, the narrow focus of studying single genes has not yet led to explanations for the myriad changes that occur in neurodegenerative diseases and aging

After completing their animal research, the researchers turned their attention to humans. They looked at changes in human genes from ages 30 to 49, 50 to 69, and then 70 and over.

By the time humans reached middle age there were already measurable changes in gene activity based on gene length.

“It seems like something is already happening early in life, but it becomes more pronounced with age,” Dr. Stoeger said.

“It seems that, at a young age, our cells are able to counteract perturbations that would lead to an imbalance in gene activity. Then, all of a sudden, our cells can no longer counteract it.”

Luis Amaral of Northwestern, lead author of the study, said: “The result for humans is very strong because we have more samples for humans than for other animals.

“It was also interesting because all the mice we studied are genetically identical, of the same gender and raised in the same laboratory conditions, but humans are all different.

“They all died of different causes and at different ages. We analyzed male and female samples separately and found the same pattern.”

But the scientists found that with aging, cell activity shifts toward shorter genes, upsetting the balance.

This is counteracted in people with very long genes, because they have longer proteins available in their cells.

Dr Stoeger said: “The changes in gene activity are very, very small, and these small changes involve thousands of genes.

“We found that this change was consistent in different tissues and in different animals.”

Scientists hope the study, published in Nature Aging, will stimulate the development of therapies to slow or reverse aging.

Medicines now target the symptoms rather than the causes of aging, which Northwestern experts said was like using painkillers to bring down a fever.

Dr Amaral said: “Fever can occur for many, many reasons. It can be caused by an infection, which requires antibiotics to heal, or appendicitis, which requires surgery.

‘Here, it’s the same. The problem is the imbalance of gene activity. If you can help correct the imbalance, you can address the downstream consequences.