Scientists crack aging mystery: Gene length is the deciding factor

Scientists believe they’ve cracked the secret of aging.

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

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

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

Dr Thomas Stoeger, lead author of the study from Northwestern University in Illinois, said: ‘I find it very elegant that a single, relatively concise principle seems to account for nearly all of the changes in the activity of genes that happen in animals as they age.’

The length of a gene is based on the number of nucleotides within it. Each string of nucleotides translates to an amino acid, forming a protein.

Therefore a very long gene yields a large protein, and a short gene yields a small protein. A cell needs to have a balanced number of small and large proteins to achieve homeostasis, and problems occur when that balance gets out of whack. 

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

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

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

This means that not just a small subset of genes that contributes to aging. Aging, instead, is characterized by systems-level changes.

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

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

And while some diseases, such as hemophilia, do result from single gene mutations, the narrow approach to studying single genes has yet to lead 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 older. 

Measurable changes in gene activity according to gene length already occurred by the time humans reached middle age.

 ‘There already seems to be something 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 counter perturbations that would lead to an imbalance in gene activity. Then, suddenly, our cells can no longer counter it.’

Northwestern’s Luis Amaral, a senior 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, the same gender and raised in the same laboratory conditions, but the humans are all different. 

‘They all died from different causes and at different ages. We analyzed samples from men and women separately and found the same pattern.’

But the scientists found that with aging activity within cells shifts towards shorter genes, upsetting the balance.

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

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

‘We found this change was consistent across different tissues and in different animals.’

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

Currently, medications target symptoms rather than the causes of getting older which the Northwestern experts said was like using painkillers to reduce a fever.

Dr Amaral said: ‘Fevers can occur for many, many reasons. It could be caused by an infection, which requires antibiotics to cure, or caused by appendicitis, which requires surgery.

‘Here, it is the same thing. The issue is the gene activity imbalance. If you can help correct the imbalance, then you can address the downstream consequences.’