Summary: In older adults, major depression is associated with accelerated mitochondrial aging.
Source: UConn
Depression often saps energy and motivation. In older adults, new research suggests a biological explanation: major depression is linked to deterioration of mitochondria, the tiny energy-producing structures inside cells.
Mitochondria serve several vital roles in cells, foremost among them generating the energy molecule ATP that cells use to function. When mitochondria become impaired, cellular performance declines and whole-body health can be affected. While inherited mitochondrial disorders such as Alper’s disease and Barth syndrome are typically evident in infancy or childhood, scientists are increasingly identifying subtle mitochondrial dysfunction as a factor in age-related conditions.
A multi-institutional team led by UConn School of Medicine student Emma Mastrobattista and Breno S. Diniz, an associate professor of psychiatry and member of the UConn Center on Aging, published findings in the American Journal of Geriatric Psychiatry showing that older adults with major depressive disorder (MDD) commonly exhibit signs of accelerated mitochondrial aging.
The researchers measured circulating levels of a mitochondria-related protein called growth differentiation factor-15 (GDF-15) in the blood of adults over 70. GDF-15 is increasingly recognized as a marker of mitochondrial stress and age-related biological change: higher circulating concentrations are associated with older chronological age, diminished cellular repair activity, and elevated health risks. In this study, higher GDF-15 levels corresponded with greater mitochondrial impairment, indicating that cellular energy systems are more compromised in depressed older adults.
This study is the largest to date linking accelerated mitochondrial aging with late-life depression, and it adds to a growing body of evidence that depression in older age is associated with multiple markers of accelerated biological aging. Earlier studies have reported similar patterns in immune cells, glial cells in the brain, and adipose tissue, suggesting a systemic pattern of cellular senescence among older adults with major depression.
“We observe changes across many cell types,” says Diniz. “Overall, older adults with major depression show signs of accelerated cellular aging throughout the body.” He notes that these interconnected changes can compound over time, so that a small initial problem can escalate into broader impairment of health, mood, and physical function.
Beyond describing this association, researchers are actively exploring interventions aimed at improving mitochondrial function and clearing senescent cells. These strategies range from lifestyle and pharmacological approaches that support mitochondrial health to experimental therapies known as senolytics, which selectively target and remove aged, dysfunctional cells. Early investigations aim to determine whether improving mitochondrial performance or reducing cellular senescence can slow or reverse aspects of biological aging and thereby improve mood, energy, cognitive functioning, and physical strength in older adults.
About this genetics and depression research news
Author: Kim Krieger
Source: UConn
Contact: Kim Krieger – UConn
Image: The image is in the public domain
Original Research: Closed access.
“Late-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine” by Emma Mastrobattista et al. American Journal of Geriatric Psychiatry
Abstract
Late-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine
Objective
Major depressive disorder in later life is linked to faster physiological and cognitive aging, which has prompted interest in identifying biological pathways that could be targeted to reduce these effects. Growth differentiation factor-15 (GDF-15) is a circulating protein implicated in biological aging through several pathways relevant to age-related disease. Higher GDF-15 levels have been associated with advancing age, reduced telomerase activity, and greater risk of adverse outcomes in older adults. This study evaluated circulating GDF-15 in older adults with MDD and examined its relationships with depression severity, burden of physical comorbidities, age at first depressive episode, and cognitive performance.
Design
The investigators measured circulating GDF-15 in a cohort of 393 older adults (mean age 70 ± 6.6 years; male to female ratio 1:1.54), including 308 participants diagnosed with MDD and 85 non-depressed comparison participants.
Results
After accounting for potential confounders, older adults with depression had significantly higher serum GDF-15 levels (mean 640.1 ± 501.5 ng/mL) compared with the non-depressed comparison group (mean 431.90 ± 223.35 ng/mL) (t = 3.75, d.f. = 391, p = 0.0002). Within the depressed group, individuals with elevated GDF-15 showed greater physical comorbidity, poorer executive cognitive functioning, and a higher likelihood of late-onset depression.
Conclusion
These findings indicate that late-life depression is associated with higher circulating levels of GDF-15, a marker linked to amplified age-related biological changes. GDF-15 represents a promising and potentially modifiable biological pathway connecting depression and accelerated aging, including cognitive decline. Future research will need to determine whether interventions that target mitochondrial health or remove senescent cells can meaningfully improve clinical outcomes for older adults with depression.