A recent study published in Science Advances suggests that traumatic events in childhood can influence physical health in old age. The research found that older adults who had experienced such adversities had diminished muscle metabolism. This association was measured through mitochondrial functions within the skeletal muscles, showing a significant connection between early stress and later life physical decline.
Previous research has consistently shown that early life stress can lead to a myriad of health problems in adulthood. However, the underlying mechanisms of this connection are not fully understood. One promising area of research focuses on mitochondrial function—essentially, the powerhouses of the cells, which generate energy necessary for cellular activities. Mitochondria respond dynamically to psychological stress, which can ultimately affect their function and contribute to health issues as one ages.
Given the gaps in existing research, particularly regarding tissue-specific measures of mitochondrial function, this study, led by University of Michigan Institute for Social Research scientist Kate Duchowny, aimed to directly assess how early childhood stress impacts mitochondrial function in skeletal muscle as individuals grow older.
To do this, the researchers utilized data from the Study of Muscle, Mobility, and Aging (SOMMA), which included participants recruited from multiple centers, including the University of Pittsburgh and Wake Forest University School of Medicine. The inclusion criteria were quite specific: participants had to be 70 years or older, have a body mass index (BMI) of 40 or less, be free from dementia, and capable of undergoing muscle tissue biopsy and magnetic resonance spectroscopy. Additionally, they had to demonstrate the ability to walk 400 meters, ensuring they had a certain level of physical mobility.
Participants in the study underwent a detailed clinical assessment, which included donating muscle and fat tissue samples. These samples were crucial for assessing mitochondrial function directly from skeletal muscle. Alongside the biological assessments, participants completed extensive questionnaires that included a modified version of the Adverse Childhood Experiences questionnaire. This questionnaire is designed to capture various dimensions of childhood adversity, such as emotional and physical abuse, neglect, and household dysfunction.
The primary finding of the research was that individuals who reported more adverse experiences during childhood demonstrated lower levels of adenosine triphosphate (ATP) production in their muscle tissues. ATP is crucial for cellular energy, and its production is a direct indicator of mitochondrial health and efficiency.
These findings are particularly important because they link early emotional and physical stressors to specific physiological outcomes that have significant implications for aging and health. Lower mitochondrial function can contribute to decreased muscle strength, reduced endurance, and a greater likelihood of frailty in older adults.
“What these results suggest is that these early formative childhood experiences have the ability to get under the skin and influence skeletal muscle mitochondria, which is important because mitochondrial function is related to a host of aging-related outcomes,” Duchowny said. “If you have compromised mitochondrial function, that doesn’t bode well for a range of health outcomes, including everything from chronic conditions to physical function and disability limitations.”
The researchers quantitatively assessed mitochondrial function by examining the maximum capacity for ATP production (ATPmax) in vivo using 31-phosphorous magnetic resonance spectroscopy (31P MRS) and examining oxidative phosphorylation capacity ex vivo through tissue samples.
“You can think about oxygen consumption rate as a way to measure the flow of electrons that’s going through the electron transport train, and it’s these electrons that generate the membrane potential that drives the synthesis of ATP,” Molina said. “It’s a really precise way of assessing mitochondrial bioenergetic capacity,” explained study co-author Anthony Molina, a professor of medicine at the University of California San Diego.
Contrary to what one might expect, the researchers found no significant association between childhood adversity and the maximum capacity for oxidative phosphorylation (Max OXPHOS) in skeletal muscle. This indicates that while ATP production is affected by early life stress, the overall capacity of the electron transport chain (which contributes to oxidative phosphorylation) might remain unaffected.
Interestingly, the researchers found that the negative impact of childhood adversity on ATP production was more pronounced in men than in women. This gender difference suggests that early life stress may interact differently with biological mechanisms in men and women, potentially due to physiological, hormonal, or even social factors.
Importantly, the results remained statistically significant even after adjusting for several potential confounding factors, including age, educational background of the parents, and the participants’ own educational attainment. This adjustment process strengthens the validity of the association between childhood adversity and mitochondrial dysfunction, suggesting that the relationship is robust despite variations in socioeconomic background and age-related factors.
“All of my previous studies have been focused on contemporaneous measures: mitochondria and physical function, mitochondria and cognitive function,” Molina said. “These studies have shown that these measures are strongly related to our strength, fitness and numerous conditions that impact physical ability.”
“I’ve also shown that these measures are related to cognitive ability and dementia. But here’s the first time we’re looking backwards, at what kinds of things that could lead to those differences in mitochondrial function that we know can drive differences in healthy aging outcomes among older adults.”
Overall, the study provides a deeper understanding of why adverse experiences in childhood might have enduring effects on physical health. But, as with any study, there are some limitations to consider. The data was cross-sectional, meaning it captured a single moment in time, which makes it difficult to definitively determine causality.
Additionally, the retrospective nature of the ACEs assessment might introduce recall bias, where participants may not accurately remember or may underreport their childhood difficulties. The predominantly white, older, and better-educated sample may also limit the generalizability of the findings.
Future research should look to longitudinal studies to better trace the causal pathways between early stress and later life health outcomes. It will also be important to examine these relationships in more diverse populations and through different types of biological measures to paint a clearer picture of the mechanisms at play.
The study, “Childhood adverse life events and skeletal muscle mitochondrial function,” was authored by Kate A. Duchowny, David J. Marcinek, Theresa Mau, L. Grisell Diaz-Ramirez, Li-Yung Lui, Frederico G. S. Toledo, Peggy M. Cawthon, Russell T. Hepple, Philip A. Kramer, Anne B. Newman, Stephen B. Kritchevsky, Steven R. Cummings, Paul M. Coen, and Anthony J. A. Molina.
