Have you ever felt like one extremely stressful activity “took 5 years off your life”? Scientists are actually studying the intricate genetic relationship between depression, stress, and longevity, targeting and identifying genes at the forefront of accelerating the aging process.
In an elaborate study narrowing down the genes most involved in mood disorders and the stress response, researchers from Indiana University identified a gene called ANK3 as the highest scoring gene on their analysis of 347 human genes similar to the 231 Caenorhabditis elegans
genes that changed after exposure to an antidepressive drug called mianserin. ANK3 and others appeared in an analysis of genomes from 3,577 older adults. Previous studies also with C. elegans
found that the worms’ lifespans increased after exposure to mianserin, and this study served to understand the genetic relationship that produces this effect.
is a species of nematode, commonly used as a model organism in science because of the similarities it shares to many other organisms in terms of classic biological processes and characteristics.
After identifying ANK3 as playing a large role in reducing longevity in cases of mood disorders and chronic stress, the researchers used C. elegans
ANK3 knockout mutants to observe any changes that might occur per the effect of mianserin and oxidative stress. Compared to normal worms with active ANK3, the team realized that ANK3 must be present in order to have a complete effect on longevity. The antidepressant drug mianserin works by keeping “youthful,” low levels ANK3 in the cells.
The researchers also looked at more than 700 blood samples from human patients, those diagnosed with psychiatric disorders and those who had died by suicide. Scientists know that genes change in expression as people get older and in people who experience intense mood or stress disorders. From this study, scientists believe that people with mood and stress disorders experience the same changes in gene expression as people who are experiencing side effects from aging because the genetic problems underlying these disorders are causing premature aging and reducing longevity.
Of the 700+ blood samples collected from human participants, what the scientists believed about genes like ANK3 and longevity was confirmed. Older patients showed much higher expression of ANK3 than younger patients, and they saw a “shift towards higher ANK3” expression in those samples from people who died by suicide.
Interestingly, the scientists also compared their findings to independently-reported cases of higher levels of ANK3 in individuals with an accelerating aging condition called Hutchinson-Gilford progeria syndrome.
The findings from their study has the scientists encouraged that they are on the way to identifying target genes for people who suffer from mood and stress disorders, to prevent them from experiencing accelerated aging and reduced longevity. While the scientists are beginning to understand the connection between ANK3 and longevity as well as a link to mitochondrial dysfunction, there are still a lot of unanswered questions that they plan to tackle.
"These studies uncover ANK3 and other genes in our dataset as biological links between mood, stress and lifespan, that may be biomarkers for biological age as well as targets for personalized preventive or therapeutic interventions."
Their study was recently published in Molecular Psychiatry.
Source: Indiana University
, University of Minnesota