Mitochondria may metabolize ADP differently in aging muscle, despite exercise resistance

March 13, 2018, Cell Press
Mitochondria. Credit: Wikipedia commons

Most adults reach their peak levels of muscle mass in their late 30s or early 40s. Even for those who exercise regularly, strength and function start to decline after that point. For those who don't exercise, the drops can be dramatic. Now, a study of twenty men published March 13 in the journal Cell Reports provides new clues about the cellular mechanisms of aging muscles, showing a key role for how mitochondria, the powerhouses of the cell, process ADP, which provides energy to cells.

ADP, or adenosine diphosphate, plays a role in how our cells release and store energy. But previous lab models that have looked at the mechanisms of aging in human have not included ADP. When ADP is metabolized in the mitochondria, it stimulates cellular respiration and decreases reactive oxidative species (ROS; also known as free radicals). Higher ROS levels are linked to damage in different components of the cell, a process also called oxidative stress.

In the study, the investigators developed an in vitro system employing individual muscle fibers taken from muscle biopsies. The fibers were put into a system in which mitochondrial function and respiration could be measured across a range of ADP concentrations that are relevant to those found in the human body. "The way people normally measure ROS is in a system that has ADP removed," says senior author Graham Holloway, an associate professor at the University of Guelph in Ontario. "But biologically, we always have ADP in the system. We started to think that maybe how we get ADP into the mitochondria is important for aging."

In the first part of the paper, the researchers compared muscle from ten healthy men in their 20s with muscle from ten healthy men in their early 70s. They found that there was an 8- to 10-fold decrease in ADP sensitivity, and therefore, when ADP was added to the system, there was a 2- to 3-fold higher rate of ROS emission in the muscle taken from the . ROS levels were determined by measuring emissions of hydrogen peroxide, a byproduct of activity in the cell.

The findings suggested that mitochondrial ADP sensitivity was somehow impaired in the muscles of the older men and that increased levels of ROS were contributing to sarcopenia, or the degenerative loss of . "The magnitude of change was quite striking to us," Holloway explains. "For humans, it's remarkable to have such a big difference."

In the second part, the older men undertook a program of supervised resistance training, which included leg presses and upper-body exercises. But, after 12 weeks, there were no changes in the levels of emitted, suggesting no improvements in age-associated cellular stress.

"This doesn't mean there's no hope for building strength in aging ," Holloway says. "I actually think that endurance training would be potentially beneficial, because we know with that kind of training you get increases in mitochondrial content." Endurance training includes aerobic exercise like cycling and swimming. "Moving forward, we plan to look at other types of exercise, to see if it can improve the dynamic response of mitochondria to ADP," he adds.

Other future work will use rodent models to delve into the cause-and-effect relationships of the molecular mechanisms of ADP metabolism. The investigators also plan to extend their studies to looking at different types of exercise in aging women. Early research in healthy young people has indicated that there are differences in sensitivity to ADP between men and women.

Explore further: Scientists find power switch for muscles

More information: Cell Reports, Holloway et al. "Age-associated impairments in mitochondrial ADP sensitivity contribute to redox stress in senescent human skeletal muscle." , DOI: 10.1016/j.celrep.2018.02.069

Related Stories

Scientists find power switch for muscles

March 6, 2018
If you've ever wondered how strenuous exercise translates into better endurance, researchers at the Salk Institute may have your answer. In a study published in the journal Cell Reports on March 6, 2018, scientists in Ronald ...

How exercise—interval training in particular—helps your mitochondria stave off old age

March 7, 2017
It's oft-repeated but true: exercise keeps you healthy. It boosts your immune system, keeps the mind sharp, helps you sleep, maintains your muscle tone, and extends your healthy lifespan. Researchers have long suspected that ...

Calorie reduction + exercise = better muscle function in older adults

August 29, 2017
Improved muscle performance starts with better mitochondrial function. Older adults who are overweight may improve their muscle function with a weight loss program that combines exercise and calorie reduction, according to ...

Exercise: the cellular 'fountain of youth'

March 28, 2017
(HealthDay)—High-intensity exercise may help older adults reverse certain aspects of the "cellular" aging process, a new study suggests.

Exercise can make cells healthier, promoting longer life, study finds

September 22, 2017
Whether it's running, walking, cycling, swimming or rowing, it's been well-known since ancient times that doing some form of aerobic exercise is essential to good health and well-being. You can lose weight, sleep better, ...

Longevity and human health may be linked to a muscle cell enzyme

June 24, 2016
Exercise and fasting do not change the location of a key enzyme involved in energy production, a study in Experimental Physiology found.

Recommended for you

Democratizing science: Researchers make neuroscience experiments easier to share, reproduce

March 16, 2018
Over the past few years, scientists have faced a problem: They often cannot reproduce the results of experiments done by themselves or their peers.

Human 'chimeric' cells restore crucial protein in Duchenne muscular dystrophy

March 16, 2018
Cells made by fusing a normal human muscle cell with a muscle cell from a person with Duchenne muscular dystrophy —a rare but fatal form of muscular dystrophy—were able to significantly improve muscle function when implanted ...

Team develops 3-D tissue model of a developing human heart

March 16, 2018
The heart is the first organ to develop in the womb and the first cause of concern for many parents.

Genetic variant discovery to help asthma sufferers

March 16, 2018
Research from the University of Liverpool, published today in Lancet Respiratory Medicine, identifies a genetic variant that could improve the safety and effectiveness of corticosteroids, drugs that are used to treat a range ...

Researchers say use of artificial intelligence in medicine raises ethical questions

March 15, 2018
In a perspective piece, Stanford researchers discuss the ethical implications of using machine-learning tools in making health care decisions for patients.

Study identifies potential drug for treatment of debilitating inherited neurological disease

March 15, 2018
St. Jude Children's Research Hospital scientists have demonstrated in mouse studies that the neurological disease spinal bulbar muscular atrophy (SBMA) can be successfully treated with drugs. The finding paves the way for ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.