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Brain health may literally be a state of mind

Having more positive experiences in life can greatly improve your brain health, according to a new study led by Columbia University.

The researchers found that positive psychosocial experiences are associated with slower age-related cognitive decline, a lower risk of developing brain disorders like Alzheimer’s disease, and even a longer life. 

However, the underlying molecular pathways – which translate these feelings and experiences into physical changes in the brain – remain unclear. 

The role of mitochondria 

The research suggests that mitochondria in the brain may play a crucial role. According to the experts, the molecular machinery used by mitochondria to transform energy is enhanced in older adults who experienced less psychological stress during their lives compared to those with more negative experiences.

“We’re showing that older individuals’ state of mind is linked to the biology of their brain mitochondria, which is the first time that subjective psychosocial experiences have been related to brain biology,” said Caroline Trumpff, an assistant professor of medical psychology at Columbia

Trumpff led the research together with Martin Picard, an associate professor of behavioral medicine at the same university.

Focus of the study

The experts analyzed data from two extensive studies involving nearly 450 older adults in the United States, collecting detailed psychosocial information over two decades. Participants donated their brains after death for further analysis, providing data on the state of their brain cells. 

Trumpff created indices that converted reports of positive and negative psychosocial factors into a single score of overall psychosocial experience. She also scored each participant on seven domains representing distinct genetic networks active in mitochondria.

“The use of multivariate mitotype indices is an important innovation because we could more easily interpret the biological state of the mitochondria with networks of related genes than an analysis of thousands of individual genes,” Picard explained. 

Abundance of proteins in mitochondria 

The results showed that one mitochondrial domain, assessing the organelle’s energy transformation machinery, was associated with psychosocial scores. 

“Greater well-being was linked to greater abundance of proteins in mitochondria needed to transform energy, whereas negative mood was linked to lower protein content,” noted Trumpff.

Brain health on a cellular level

The researchers also analyzed mitochondria in specific brain cell types and found that the associations between mitochondria and psychosocial factors were driven not by the brain’s neurons but its glial cells. 

“This piece of the study, made possible by our collaboration with the Columbia Center for Translational and Computational Neuroimmunology, is what I think makes it particularly significant,” Picard said. 

“To ask questions at this level of cellular resolution in the brain is unprecedented in the mitochondrial field. Neurons have been the focus of neuroscience, but we’re waking up to the fact that other cells in the brain may be driving disease.”

Mitochondria, mood, and brain health

The study cannot determine whether the participant’s psychosocial experiences altered their brain mitochondria or if innate or acquired mitochondrial states contributed to those experiences. However, other studies suggest that the relationship between mitochondria and mood works both ways. 

In animal studies, for instance, chronic stress has been shown to affect mitochondrial energy transformation. 

Moreover, a recent study conducted by Picard and collaborator Elissa Epel at the University of California, San Francisco found that positive mood predicted greater mitochondrial energy production in participants’ blood cells on subsequent days.

Measuring the brain’s mitochondrial health 

Trumpff and Picard are currently studying whether increased energy transformation machinery leads to greater energy transformation in the brain’s mitochondria. They are also exploring ways to measure the brain’s mitochondrial health, which could be used in doctors’ offices in the future.

“Mitochondria are the source of health and life, but we don’t have ways to quantify health, only disease,” Picard explained. “We need a science of health. We need tests that show how healthy and resilient someone is.” 

“This would be valuable clinically to monitor changes in health before the appearance of disease, and it could transform medical research by giving scientists something to target other than decades of accumulated protein deposits or other forms of long-term damage.”

The study is published in the journal Proceedings of the National Academy of Sciences.


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