Summary: In older adults, major depression has been linked to mitochondrial deterioration.
Depression can drain a person’s energy. In the elderly, there may be a very good reason for that: depression has been linked with the deterioration of the tiny power plants in our cells.
These power plants are the mitochondria, tiny structures within our cells that handle several important tasks. The most critical is producing the molecules our cells use for energy. When mitochondria don’t function well, it causes all kinds of problems for us. Mitochondrial diseases such as Alper’s disease and Barth syndrome are the best known and usually become obvious in infancy or childhood. But researchers are now finding other effects.
Major depression, for example. A team of researchers from several institutions, led by UConn School of Medicine student Emma Mastrobattista and Breno S. Diniz, an associate professor in psychiatry and the UConn Center on Aging, reports in the American Journal of Geriatric Psychiatry that older adults with major depression often have rapidly aging mitochondria.
The team measured levels of a protein produced by mitochondria in the blood of depressed adults over 70. The protein, GDF-15, is strongly associated with aging, poorly functioning mitochondria. And aging mitochondria are strongly linked with fast biological aging. The higher the level of GDF-15 in the blood, the more impaired the mitochondria tend to be. In other words, this is when our tiny power plants start to fall apart.
The team measured levels of a protein produced by mitochondria in the blood of depressed adults over 70. Image is in the public domain
This is the largest study to date providing a link between accelerated mitochondrial aging and depression in older adults, but the scientists were not surprised. Previous work has shown other aspects of accelerated aging are correlated with major depression.
“We have seen it in immune cells; in glial cells in the brain; in adipose tissue. We see a systemic cellular senescence changes in depressed older adults,” says Diniz, meaning overall, older adults with major depression show accelerated aging in cells throughout their body.
“One problem feeds into another, and make what began as a small issue into a much larger one,” he says.
The researchers have begun testing interventions that improve mitochondrial function and clear senescence in humans in hopes that they may slow or even reverse biological aging. They are also collaborating with partners working with senolytics, experimental drugs that selectively remove aged, malfunctioning cells, in the hopes of improving mood, strength, and energy in older adults.
Late-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine
In older adults, major depressive disorder (MDD) is associated with accelerated physiological and cognitive aging, generating interest in uncovering biological pathways that may be targetable by interventions. Growth differentiation factor-15 (GDF-15) plays a significant role in biological aging via multiple biological pathways relevant to age and age-related diseases. Elevated levels of GDF-15 correlate with increasing chronological age, decreased telomerase activity, and increased mortality risk in older adults. We sought to evaluate the circulating levels of GDF-15 in older adults with MDD and its association with depression severity, physical comorbidity burden, age of onset of first depressive episode, and cognitive performance.
This study assayed circulating levels of GDF-15 in 393 older adults (mean ± SD age 70 ± 6.6 years, male:female ratio 1:1.54), 308 with MDD and 85 non-depressed comparison individuals.
After adjusting for confounding variables, depressed older adults had significantly higher GDF-15 serum levels (640.1 ± 501.5 ng/mL) than comparison individuals (431.90 ± 223.35 ng/mL) (t=3.75, d.f.= 391, p=0.0002). Among depressed individuals, those with high GDF-15 had higher levels of comorbid physical illness, lower executive cognitive functioning, and higher likelihood of having late-onset depression.
Our results suggest that depression in late life is associated with GDF-15, a marker of amplified age-related biological changes. GDF-15 is a novel and potentially targetable biological pathway between depression and accelerated aging, including cognitive aging.