Languishing Cellular Batteries Foretell Movement Problems
Tuesday, April 19, 2022
Measuring the function of cellular energy-producers called mitochondria could allow doctors to predict the decline of physical abilities in older adults, according to recent IRP research.
Throughout human history, people have sought insight into their fates from self-proclaimed psychics and other dubious fortune tellers. Fortunately, scientists are increasingly developing more reliable, data-driven ways to predict the future. For instance, IRP researchers recently showed that an assessment of the cellular batteries that power our muscles can predict the deterioration of physical abilities in older adults.1
Most people find themselves slowing down considerably as they age, and many older adults require a cane or other assistive device to help them get from point A to point B. This sort of physical decline is not only inconvenient and potentially frustrating, but it is also a powerful predictor of future health outcomes, as those who slow down the most are more likely to develop Alzheimer’s disease and are at higher risk of dying in general. For this reason, measuring the walking speed of older adults can help inform doctors about their patients’ physical and cognitive health.
Of course, such walking tests only provide information about a patient in the present, but researchers like IRP staff scientist Qu Tian, Ph.D., are working on ways to more quickly identify individuals whose walking speed is slowing, formally referred to as ‘mobility decline.’ Dr. Tian and her colleagues in the lab of IRP senior investigator Luigi Ferrucci, M.D., Ph.D., are particularly focused on the idea that scrutinizing the energy-producing mitochondria that power our muscle cells could permit them to predict age-related mobility decline.
“Mitochondrial function declines with aging, and this mitochondrial decline has been identified as a hallmark of aging,” Dr. Tian says. “Mitochondria play an important role in all cells of the body, but they are particularly critical in tissue that requires a lot of energy, such as the central nervous system, the musculoskeletal system, and the cardiovascular system, which are very important for healthy aging.”
Mitochondria, pictured above, use oxygen along with other substances to produce the energy that allows muscles to move.
The IRP researchers put their theory to the test using data from the Baltimore Longitudinal Study of Aging (BLSA), a study of human aging that has been collecting data since 1958. They specifically examined four measurements of participants’ walking speed collected as part of the BLSA between 2013 and 2019, as well as a test of how well the mitochondria in their muscles worked. The latter was measured by having participants perform a knee extension exercise to exhaustion and then using a cutting-edge imaging technique to calculate how rapidly the mitochondria in the exhausted muscle used oxygen to restore cellular energy levels, a metric known as ‘oxidative capacity.’
Dr. Qu Tian, the new study’s lead author
Dr. Tian’s study included data on 380 people ages 60 and up who had their walking speed and the oxidative capacity of their muscle mitochondria measured at the same clinic visit. All the participants were well-functioning both physically and cognitively at that time. Nearly three-quarters of them also did additional walking speed tests at least a year after their first assessment, allowing Dr. Tian and her colleagues to compare how walking speed changed over time in participants whose mitochondria had relatively higher or lower oxidative capacity at the time they did their first walking tests.
Among the participants whose walking speed was measured multiple times over the study’s time window, those with a lower mitochondrial oxidative capacity when their walking speed was assessed the first time were significantly slower on all four walking tests a year or more later. Further analysis showed that this relationship could be partially explained by changes in the strength of participants’ muscles during the period between the initial and follow-up walking tests, suggesting that mitochondrial health could influence mobility by affecting muscle strength as well as through other, still unknown mechanisms.
“The fact that we established this predictivity of lower mitochondrial function in a longitudinal study has great implications towards causality,” Dr. Tian says. “This is not an experimental study, this is not an intervention study, but the value of this study is that we were able to demonstrate the temporal sequence: mitochondrial function predicted future change in mobility decline.”
Physical activity can help keep the mitochondria in muscles healthy, and scientists are also developing drugs that can boost mitochondrial function.
If additional studies corroborate that conclusion, doctors could one day measure how well older adults’ mitochondria work in order to identify the patients at greatest risk of seeing their physical abilities significantly degrade in the future. This would then allow clinicians to prescribe interventions designed to stave off mobility decline, such as exercise regimens or medications currently in development that boost mitochondrial function.
However, few doctors have access to the high-tech imaging method used to assess mitochondrial oxidative capacity in Dr. Tian’s study, so she and her colleagues are also trying to come up with easier ways to measure mitochondrial function. Already, they have determined that the amount of mitochondrial DNA in a person’s blood is higher in those with higher mitochondrial oxidative capacity as measured by the imaging technique,2 an important first step towards a future in which doctors can predict the deterioration of their patients’ physical capacities using a simple blood test.
“Future work will be needed to understand whether these blood-based markers of mitochondrial function are associated with mobility decline,” Dr. Tian says. “Blood draw is more accessible in the clinical setting, so if that link exists, I think it may open a door for clinical use.”
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 Tian Q, Mitchell BA, Zampino M, Fischbein KW, Spencer RG, Ferrucci L. Muscle mitochondrial energetics predicts mobility decline in well-functioning older adults: The baltimore longitudinal study of aging. Aging Cell. 2022 Feb;21(2):e13552. doi: 10.1111/acel.13552.
 Tian Q, Moore AZ, Oppong R, Ding J, Zampino M, Fishbein KW, Spencer RG, Ferrucci L. Mitochondrial DNA copy number and heteroplasmy load correlate with skeletal muscle oxidative capacity by P31 MR spectroscopy. Aging Cell. 2021 Nov;20(11):e13487. doi: 10.1111/acel.13487.