Researchers Identify Genes That Reduce Life Expectancy of People Under Stress

Stress and foul mood can be detrimental to one's health and reduce one's life expectancy. Now, scientists have identified the genes responsible for reducing the life expectancy of individuals who are always under stress and do not have a happy disposition.

The study, recently published in the Molecular Psychiatry, revealed the genetic reason of this poorly understood phenomenon. Mood and stress are known to shorten the lifespan. The researchers of the study have also identified the genes responsible for it.

The researchers of the Indiana University School of Medicine and the Scripps Research Institute, CA, undertook a multi-faceted project, researching on the genetic premises of premature aging in the presence of stress and psychiatric illness.

The researchers used human respondents and a particular worm called Caenorhabditis Elegans - the most studied worm on the earth - for their research. The researchers identified a range of genes that seem to control the impact of mood and stress responses on the longevity of an organism. The reason why the researchers chose C. Elegans is that one of the co-authors, Michael Petrascheck, Ph.D., found that when the worm was exposed to an antidepressant Mianserin, it lived longer. The latest study was based on this prior knowledge.

"We were looking for genes that might be at the interface between mood, stress, and longevity. We have found a series of genes involved in mood disorders and stress disorders which also seem to be involved in longevity," said the lead author of the study, Dr. Alexander B. Niculescu III.

Gene ANK3's key role in reducing life expectancy

The researchers zeroed in on a particular gene called ANK3 that appeared to play a key role in the process. It is a protein called Ankyrin-G which is involved in certain types of synaptic transmission between neurons. Ankyrin-G was also found to be associated with bipolar disorder, autism and schizophrenia. This gene is a vital link for unearthing the association between emotional responses and premature aging.

The researchers found that these genes changed their rates of expression with age. The genes showed a significant shift in expression in people who experienced stress or mood disorders, and also in people who had committed suicide. This shift or change is normally associated with shorter lifespan and premature aging.

Modus operandi

The researchers did a thorough research to study the role of genes in altering the mood, stress and lifespan.

  • They first investigated the genetic changes Mianserin made to C. Elegans that affected 231 genes, which were then compared to the human genome. They found at least 347 corresponding genes in humans.
  • The researchers then compared these 347 genes with the genomes of 3,577 older adults and found that 134 of them overlapped with depressive symptoms in humans.
  • They then studied the C. Elegans and tested them under the effects of Mianserin and oxidative stress. ANK3 is set to increase with age and the drug keeps these levels down. However, they found that Mianserin needs at least some ANK3 to provide its life-extending effects.
  • While studying 700 blood samples from psychiatric patients and people who had committed suicide, the researchers found higher levels of ANK3 in older patients and those who had committed suicide.
  • They collected a panel of biomarkers by adding some of the other high-scoring genes from Niculescu lab's Convergent Functional Genomics investigation. As a group, they gave an even stronger result than ANK3 on its own. The correlation was stronger for the suicide group.

Link between genes and longevity

It was revealed that the genes that overlapped most with mood- and stress-modulated longevity are associated with mitochondrial dysfunction. And mitochondrial dysfunction and aging are closely linked, according to the researchers.