There's a tiny, slow-burning 'fuse' attached to the ends of all our chromosomes, and as we naturally age, each of our cells loses more and more of that life-giving line.
Researchers in South Korea have now shown this fuse, known as the telomere, is unusually short in the cells of elderly people who are relatively healthy but have noticed early signs of depressive symptoms and cognitive decline, such as memory loss.
The randomized controlled trial presents more evidence for the telomere hypothesis of aging, which posits that all cells hit a point where they can no longer divide and replicate.
Telomeres are repetitive sequences of DNA that form protective 'caps' on the ends of a cell's chromosomes. Each time the cell divides and replicates, telomeres grow a little shorter, and their protective qualities dwindle.
When telomeres finally reach their end, the cell stops dividing and enters a zombie-like state.
According to the hypothesis, if the body's recycling system doesn't clear out these zombie cells, the undead can form an 'army' that may contribute to disease just about anywhere in the body.
Whether or not you accept this hypothesis, it is clear that the shrinking telomere is closely related to aging, not just for the cell but for the entire organism.
The physical toll that chronic depression can take or its links to inflammation have been used to explain why aging is accelerated in the brains and telomeres of some older individuals.
And the new research from South Korea backs up that interpretation, even for what could be depression in its early stages.
The trial included 137 volunteers between the ages of 60 and 79 years old. Ultimately, those who experienced symptoms of depression and complained of cognitive issues were more likely to possess shorter telomeres.
These shorter telomeres were also related to increased levels of interleukin-6 (IL-6), which can act as a pro-inflammatory cytokine, as well as an anti-inflammatory myokine in the blood.
"Based on our findings, we believe that telomere length shortening in elderly is not only associated with advanced depression but also with early depressive symptoms," write neurosurgeon Myung-Hoon Han of Hanyang University Guri Hospital and colleagues.
"Telomere length shortening is associated with increased IL-6 levels in the elderly, and we speculate that IL-6 may be a cytokine involved in depression from the early stages to advanced depression."
Chronic inflammation has become a leading suspect in many age-related diseases in recent years, including Alzheimer's.
Today, depression is known to significantly increase the risk of developing Alzheimer's, and increased inflammatory markers like IL-6 have been tied to dementia.
"The precise mechanism underlying the correlation of shorter [telomeres] with depression, cognitive decline, and inflammatory cytokines remains unclear," the researchers admit.
But that's just a correlation, and it doesn't tell scientists which way the cause and effect runs. In all likelihood, though, these are criss-crossing, two-way streets.
Cells that have shortened telomeres, for instance, are more likely to secrete pro-inflammatory cytokines like IL-6. Meanwhile, chronic low-grade inflammation seems to shorten telomeres at a more rapid rate.
"This repeated process may cause cumulative structural and functional changes in the brain, leading to cognitive impairment and mood disorders including depression," the researchers explain.
The results of the recent randomized trial will need to be replicated among larger cohorts, but the authors are hopeful their findings could go some way to helping predict depression in elderly individuals before it can take its toll.
The study was published in Aging.