Association between Premature Aging and Mood and Stress

Research team from Indiana University School of Medicine and the Scripps Research Institute, discovers the genetic base of an improperly understood phenomenon. Mood and stress are well-known to play a role to reduced lifespan, and investigators may now have discovered the genes that are involved.

A detailed study maps the genetics engaged in the reducing of life in reaction to mood and stress.
A detailed study maps the genetics engaged in the reducing of life in reaction to mood and stress.

This new research presented recently in Molecular Psychiatry and conducted a multifaceted project analyzing the genetic basis of early aging in reaction to stress and psychiatric conditions.

Using humans and Caenorhabditis elegans, one of planet Earth’s most studied worms, the investigators studied into this intractable question.

They managed to determine a raft of genes that look to control the effect of mood and stress reactions on the longevity of an organism.

A gene known as ANK3 was of specific interest and seemed to perform a key part in the process.

The role of ANK3

ANK3 codes for a protein known as ankyrin-G. This protein is engaged in specific forms of synaptic transmission. Ankyrin-G has earlier been linked with bipolar disorder, autism, and schizophrenia.

This gene is a primary candidate for discovering the associations between emotional reactions and early aging.

Lead author Dr. Alexander B. Niculescu III states:

“We were searching for genes that might be at the interface between mood, stress, and longevity. We have identified a set of genes engaged in mood disorders and stress disorders which also look to be engaged in longevity.”

After examining the genes even more, Dr. Niculescu and his research team identified that the genes in question changed their rates of expression with age. When analyzing the genes of people who experienced major stress or mood disorders – for example, individuals who had committed suicide – they observed changes in the expression of these genes.

The shifts are of the kind that would generally be related with shorter lifespans and early aging.

Earlier study, performed by one of the co-authors of the present research, Michael Petrascheck, Ph.D., identified that when C. elegans was subjected to mianserin – an antidepressant – the animals survived longer. This served as the beginning point for the present project.

Stress, aging, genes, and worms

To analyze the roles of genes in mood, stress, and lifespan, the research team embarked on a extensive program of experiments:

First of all, the team researched the genetic modifications mianserin made to C. elegans. The medicine was identified to affect 231 genes that were then cross referenced to the human genome. Altogether, 347 corresponding, similar genes were recognized in humans.

These 347 genes were compared with the genomes of 3,577 older people. Of these genes, 134 overlapped with depressive symptoms in human beings.

The investigators applied a database that contains genes previously known to be included in psychiatric conditions. They also applied Niculescu lab’s Convergent Functional Genomics method to focus on the genes in order of their participation in mood and stress problems. The top scoring gene was ANK3, a gene that is getting well recognized for its role in psychiatric disorders.

Emphasis then shifted back to C. elegans. The research team used strains of the worm that had been bred with inactive ANK3 genes. These worms were examined under the effects of mianserin and oxidative stress. ANK3 is identified to raise with age and mianserin keeps these levels down. However, they identified that mianserin requires at least some ANK3 to offer its life-extending effects.

Next, 700 blood samples from psychiatric sufferers and individuals who had committed suicide were analyzed. ANK3 was identified in greater levels in older sufferers and those who had committed suicide.

A panel of biomarkers was gathered by putting some of the other high-scoring genes from the Convergent Functional Genomics research. When obtained as a group, they gave an even more powerful outcome than ANK3 on its own. The connection was especially strong for the suicide group, showing that the group of genes the team had discovered did look to play a part in psychiatric conditions.

The next concern is how these genes might affect longevity. It was demonstrated that the genes that overlapped most with mood and stress modulated longevity appeared to be engaged in mitochondrial dysfunction. This connection makes sense; an association between mitochondrial dysfunction and aging is continuously growing support from other research.

The authors of the research conclude that “these studies discover ANK3 and other genes in our dataset as biological connections between mood, stress, and lifespan that may be biomarkers for biological age along with targets for personalized preventive or therapeutic interventions.”

Like always, more work will be required to back up the results, but the thorough nature of the research and its agreement with other studies provides future investigators a powerful platform to build upon.