• What we think and feel has long been associated with health outcomes and longevity, but the biological basis for this has yet to be determined. 
  • For the first time, scientists have linked the mental state of older adults with mitochondrial energy output. 
  • The study supports therapies like NMN, which could counteract the physiological consequences of adverse mind states by preserving mitochondrial energy output. 

Factors, such as having a larger social network or purpose in life, are associated with reduced risk of mortality and higher cognitive function in older adults. In contrast, perceived social isolation, neuroticism (e.g., anxiety, anger, depression), and low conscientiousness (e.g., a lack of self-discipline) are associated with an increased risk for cognitive impairments. 

However, the biological mechanisms underlying lifespan-altering psychological states are only now being unveiled. Columbia University researchers have found that psychological experiences are associated with proteins in our mitochondria, which produce nearly all of the brain’s energy. 

“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,” says Caroline Trumpff, Ph.D., assistant professor of medical psychology, who led the research with Martin Picard, Ph.D., associate professor of behavioral medicine at Columbia University.

(Image: Columbia University) Dr. Martin Picard (center-left) and Dr. Caroline Trumpff (center-right) speaking with colleagues.

Greater Well-Being Linked to Energy-Generation 

The brain is the main organ responsible for processing our experiences to produce thoughts, emotions, and resulting behaviors. Picard’s team analyzed proteins from a brain region that modulates self-control and emotional regulation called the dorsolateral prefrontal cortex. The proteins analyzed were those involved in the function of mitochondria, which produce cellular energy, integrate cellular information, and modulate cell survival.

“We think that the mitochondria in the brain are like antennae, picking up molecular and hormonal signals and transmitting information to the cell nucleus, changing the life course of each cell,” says Picard. “And if mitochondria can change cell behavior, they can change the biology of the brain, the mind, and the whole person.”

Mitochondrial proteins were quantified from postmortem prefrontal cortex tissue donated by 450 older adults from two previous studies. As part of these studies, the participants were followed for the final decades of their lives while detailed psychosocial information was collected. As a result, the researchers found that,

“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,” Trumpff says. “This may be why chronic psychological stress and negative experiences are bad for the brain, because they damage or impair mitochondrial energy transformation in the dorsolateral prefrontal cortex, the part of the brain responsible for high-level cognitive tasks.”

Greater well-being was assessed by the following: 

  • Purpose in life
  • Personal growth
  • Positive relations with others
  • Self-acceptance
  • Autonomy and environmental mastery 

Can NMN Improve Well-Being by Targeting Mitochondria?

In the words of neuroscientist Bruce S. McEwen, reducing stress involves, 

“Changing behavior and lifestyle, for example, by improving sleep quality and quantity, improving social support, and cultivating a positive outlook on life, along with maintaining a healthy diet, avoiding smoking, and engaging in regular, moderate physical activity.” 

Still, with a better understanding of the biological basis of mental well-being, scientists are discovering potential ways to improve mood with small-molecule interventions, such as NMN. Researchers found that NMN increases cellular energy in the prefrontal cortex of mice, leading to reduced depressive-like symptoms from stress. Stress-induced depressive-like symptoms were also mitigated by NMN in another mouse study, which showed that NMN activates an NAD+-dependent enzyme called SIRT3. 

SIRT3 directly interacts with mitochondria to maintain the production of cellular energy. Therefore, activating SIRT3 with NMN may increase cellular energy levels by improving mitochondrial health. While more studies are needed, psychological stress may damage mitochondria, reducing cellular energy production. Hence, counteracting stress-induced losses in cellular energy with NMN could protect mitochondrial health, ultimately leading to better brain health and a more positive mental state.