Strengthening mitochondria through exercise: training the power plants of your cells
Mitochondria are not abstract biology. They help determine how much energy you feel in everyday life. And they are among the most adaptable structures in your body. Which training challenges them most according to studies, and why standing still is a signal of its own for them.
We talk about fatigue as if it were a question of character. Yet energy begins in a very concrete place. In trillions of tiny power plants that respond to every signal you give them.
Where does your energy actually come from?
Do you know those days when even the stairs up to your apartment feel like a mountain? You slept enough. You ate. And still your body feels like a phone at twelve percent battery.
Maybe you told yourself: "I'm just getting older." Or: "I'm simply not the sporty type." Both are understandable. But both fall short.
I'd like to offer you a different perspective. Your energy is not a fixed quantity. It is produced in your cells every second. And the factories that do this can be trained.
Mitochondria, simply explained
Imagine every muscle cell as a small city. The mitochondria are its power plants. They take building blocks from sugar and fat, burn them with oxygen and turn them into ATP. ATP is the energy currency your body uses to pay for everything: every heartbeat, every thought, every movement.
What makes them special: these power plants are not fixed installations. A city with high demand builds new power plants and modernizes the old ones. A city that hardly needs any electricity shuts some down. That is exactly what happens in your muscle. Experts call the building of new ones mitochondrial biogenesis.
Fatigue is not always a sign that you lack willpower. Sometimes it is a sign that your power plants receive demand too rarely. And demand is something you can create yourself.
And now you know why energy is not only about sleep and calories, but also about the question: How often do you challenge your cells?
What happens in your muscle when you exert yourself
You start running, your breathing quickens, your legs get warm. From the outside, this looks unspectacular. Inside, an alarm system is switching on that belongs to the most fascinating chapters of physiology.
When the muscle works, its energy reserve drops. Calcium flows, oxygen demand rises. Sensors such as the enzyme AMPK register this bottleneck. They switch on a key player: PGC-1α. Think of PGC-1α as a construction manager who sends out many building crews at once to build new mitochondria.
The stimulus
Training uses ATP faster than it can be replenished. The cell senses an energy gap.
The sensors
Signaling pathways such as AMPK and p38 sound the alarm. They activate PGC-1α and send it toward the cell nucleus.
The blueprint
In the nucleus, genes for the respiratory chain and fat burning are expressed more strongly. New components are produced.
The remodeling
If the stimulus is repeated over weeks, more and more capable mitochondria can develop.
A single workout awakens PGC-1α
A Copenhagen team led by Pilegaard, Saltin and Neufer examined muscle samples before and up to 24 hours after exercise. Expression of the PGC-1α gene rose 10 to over 40-fold, peaking within two hours after training. Remarkably, activation was even stronger in the trained leg than in the untrained one.
What this means for you: Every session sends a short, strong building signal. It fades again after a few hours. Only repetition turns many signals into remodeling.
Pilegaard H et al. Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. J Physiol. 2003;546(Pt 3):851-8. DOI: 10.1113/jphysiol.2002.034850Four short sprints and the construction manager moves into the nucleus
A Canadian group led by Little and Gibala had eight healthy men cycle four times for 30 seconds at full effort, with four minutes of rest in between. Three hours later, clearly more PGC-1α was detectable in the nucleus, at the same time as increased expression of mitochondrial genes. After 24 hours, the content and activity of mitochondrial proteins rose.
What this means for you: Even very short, intense efforts appear to be able to trigger the building cascade. It is not only about the minutes, but also about the strength of the signal.
Little JP et al. An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1α and activates mitochondrial biogenesis in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2011;300(6):R1303-10. DOI: 10.1152/ajpregu.00538.2010Supported by biopsy studies in humans: training activates PGC-1α and mitochondrial genes in muscle. Still open: exactly how short-term signals translate into long-term adaptations. A review by Granata, Jamnick and Bishop emphasizes that acute effects after a single session do not necessarily predict what remains after weeks of training.
Training is not calorie burning with sweat. It is a message to your genes. The question is not only "How much did I burn?" but "What did I tell my cells today?"
And now you know why even a single training session is biologically more than a tick in your calendar.
Intervals or steady runs: what challenges the power plants most?
Maybe you know the two camps. Some swear by long, calm runs. Others say only short, hard intervals do anything. And you stand in between, wondering what your limited time is enough for.
Research does not name a simple winner here. But it shows something more interesting: intensity and volume appear to turn different dials.
2.5 hours of sprints versus 10.5 hours of endurance
A group led by Gibala at McMaster University had 16 active young men train six times over two weeks. One group did four to six sprints of 30 seconds, the other cycled steadily for 90 to 120 minutes. Although the time commitment was about 2.5 versus 10.5 hours and training volume was roughly 90 percent lower, the oxidative capacity of the muscle rose similarly in both groups.
What this means for you: If you have little time, short, intense sessions could be an efficient way to start. The study was small and involved young, already active men.
Gibala MJ et al. Short-term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance. J Physiol. 2006;575(Pt 3):901-11. DOI: 10.1113/jphysiol.2006.112094Same work, different power plants
MacInnis and colleagues used a clever trick: ten young men trained one leg with intervals and the other leg steadily, randomly assigned and with exactly the same total work. After six sessions in two weeks, the activity of citrate synthase, a marker of mitochondrial content, was higher in the interval leg than in the continuous leg. Maximal respiratory capacity was also greater in the interval leg.
What this means for you: With the same effort, the type of load appears to make a difference. Intensity could be a building order of its own, not just a shortcut.
MacInnis MJ et al. Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work. J Physiol. 2017;595(9):2955-2968. DOI: 10.1113/JP272570Respiration and quantity are not the same
Granata and Bishop randomly assigned 29 healthy men for four weeks to sprint intervals, longer intervals or steady training below the lactate threshold. Only after the sprint intervals did maximal mitochondrial respiration rise, by 25 percent, and only there did PGC-1α content increase by 60 to 90 percent. Citrate synthase activity, as a measure of mitochondrial content, remained unchanged in all groups.
What this means for you: Your power plants can work better even without more of them appearing right away. Quality and quantity are two different adaptations.
Granata C et al. Training intensity modulates changes in PGC-1α and p53 protein content and mitochondrial respiration, but not markers of mitochondrial content in human skeletal muscle. FASEB J. 2016;30(2):959-70. DOI: 10.1096/fj.15-276907In a review, Granata, Jamnick and Bishop brought these observations together. Their conclusion: training volume appears to mainly influence mitochondrial content, while relative intensity tends to influence respiratory function. MacInnis and Gibala arrive at a similar picture in their own review. Intervals trigger the classic adaptations of endurance training, often in less time.
| Training stimulus | What it appears to do in muscle | Evidence |
|---|---|---|
| Short, intense intervals | Strong activation of PGC-1α, increase in respiratory capacity, time-efficient | RCT and biopsy studies |
| Longer intervals | At equal work, larger increases in citrate synthase and respiration than continuous training | Randomized, n=10 |
| Calm, longer endurance | Volume as a possible main driver of more mitochondria, high fat burning | Reviews |
| Combination of intervals and strength | Improved respiration, insulin sensitivity and muscle mass, also in older age | Training study, 12 weeks |
Perhaps the question "Intervals or endurance?" is the wrong question. Your power plants appear to understand two kinds of messages: "Become more" and "Become better". If you send both, you give them the full blueprint.
And now you know why smart training is usually not an either/or, but a mix.
Zone 2: the calm foundation
Maybe interval training feels like too much right now. You are exhausted, stressed or getting back into it after a long break. Then here is the good news: the calm pace is not second-class training.
In so-called Zone 2, you move in a way that still lets you hold a conversation, but you notice you are working. In this range, well-trained mitochondria burn a lot of fat and produce little lactate. Lactate is not a waste product here, but a fuel in its own right that mitochondria take up again.
Fat burning and lactate move in opposite directions
San-Millán and Brooks compared professional endurance athletes, moderately active people and people with metabolic syndrome on the ergometer. The professionals burned considerably more fat and had less lactate in their blood. Across all groups, high fat burning and low lactate were closely linked, with a correlation coefficient of minus 0.76.
What this means for you: How much fat you burn during calm exercise could be an indirect indication of how capable your mitochondria are. The authors speak of metabolic flexibility.
San-Millán I, Brooks GA. Assessment of Metabolic Flexibility by Means of Measuring Blood Lactate, Fat, and Carbohydrate Oxidation Responses to Exercise in Professional Endurance Athletes and Less-Fit Individuals. Sports Med. 2018;48(2):467-479. DOI: 10.1007/s40279-017-0751-xThe study by San-Millán and Brooks is a cross-sectional measurement, not a training study. It shows an association, not proof that Zone 2 specifically is the best intensity for mitochondria. Direct comparative studies on this are still scarce. Mechanistically, Zone 2 is plausible above all as a way to accumulate a lot of training volume with a low recovery burden. If you want to dig deeper, you will find more in the article Understanding Zone 2 training.
Slow is not the same as ineffective. For many people, the calm pace is the base on which more intense stimuli can be handled well in the first place. You don't see a foundation, but everything stands on it.
And now you know why a calm run can be more for your cells than a light balance activity.
Mitochondria in older age: fate or a question of movement?
"That's just how it is at 60." Many people hear this sentence when they run out of breath on a hike sooner than they used to. And yes, on average the power plants change over the years. But the more interesting question is: How much of that is age, and how much is standing still?
Less mitochondrial DNA, less ATP
A group led by Short and Nair at the Mayo Clinic examined muscle samples from 146 healthy people aged 18 to 89. Mitochondrial DNA and mitochondrial ATP production decreased with age. ATP production was closely linked to aerobic fitness and glucose tolerance.
What this means for you: The performance of your power plants is connected to two things you feel in everyday life. Your endurance and your blood sugar.
Short KR et al. Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci U S A. 2005;102(15):5618-23. DOI: 10.1073/pnas.0501559102Active older adults like active young adults
Distefano, Coen and colleagues compared active young adults, active older adults and inactive older adults. Mitochondrial respiration, maximal capacity and efficiency in active older adults were similar to those of active young adults. In inactive older adults they were clearly lower, and this group also needed longer to climb stairs and rise from a chair.
What this means for you: Part of what we interpret as aging of the mitochondria could to a good extent be an effect of inactivity. The study, however, shows an association, not proof of cause and effect.
Distefano G et al. Physical activity unveils the relationship between mitochondrial energetics, muscle quality, and physical function in older adults. J Cachexia Sarcopenia Muscle. 2018;9(2):279-294. DOI: 10.1002/jcsm.12272Interval training in young and older adults
Robinson, Nair and colleagues at the Mayo Clinic had younger and older adults train for twelve weeks with interval training, strength training or a combination. All three forms improved insulin sensitivity and fat-free mass, but only interval and combined training increased aerobic capacity and mitochondrial respiration. Especially in older adults, interval training appeared to reduce many age-related differences in the muscle proteome, above all in mitochondrial proteins.
What this means for you: Older muscles also appear to respond clearly to the right stimulus. Age may be less a question of whether anything happens than a question of which signal arrives.
Robinson MM et al. Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans. Cell Metab. 2017;25(3):581-592. DOI: 10.1016/j.cmet.2017.02.009A small study by Menshikova, Goodpaster and colleagues from Pittsburgh fits this picture. Eight people around 67 years old did regular endurance training. Mitochondrial DNA in muscle rose from about 1264 to 1895 copies, and the activity of the entire respiratory chain roughly doubled. Without a control group, this is a cautious indication, but an encouraging one.
people aged 18 to 89 showed, on average, declining mitochondrial ATP production with age
copies of mitochondrial DNA before and after endurance training in older adults around 67
of interval training improved mitochondrial respiration in younger and older adults
Age does not write alone how your power plants work. It co-writes. You author the other part of the text with every step you take, and with every day you stay seated.
And now you know why healthy aging at the cellular level is so closely linked to movement.
Strength training and the power plants
Maybe you prefer training with weights over cycling. Then you are right to ask: Do my mitochondria get anything out of it too?
The answer is nuanced. An Innsbruck study by Pesta, Gnaiger and colleagues followed 25 inactive adults for ten weeks. Both endurance and strength training increased the ability of mitochondria to burn fat, by 2.6-fold and 2.4-fold respectively. Most of this improvement was due to better quality of the mitochondria rather than their quantity.
In the Mayo Clinic study by Robinson, on the other hand, strength training alone did not measurably improve mitochondrial respiration, though it did improve muscle mass and insulin sensitivity. Taken together, both studies suggest: especially people who have been inactive for a long time can probably stimulate their power plants through strength training too. For a targeted mitochondrial stimulus, however, an endurance or interval component appears to be stronger.
Strength and endurance are not competitors. Muscles are where the power plants sit. More muscle means more room for mitochondria, and endurance stimuli fill that room. Together, both add up to more than the sum.
And now you know why the combination of strength and endurance performs best in many studies. You can read more about muscle as an organ in the article Strength training after 40.
When the power plants stand still: inactivity and metabolism
Think of a week with the flu, a cast after a fall or a long stretch of working from home. Afterwards, everything feels heavier. That is not your imagination.
The power plants shut down quickly
Abadi, Tarnopolsky and colleagues immobilized one leg of 24 healthy women and men for two weeks. After just 48 hours, genes for mitochondrial energy production were among the most strongly altered. After 14 days, the activities of cytochrome c oxidase and citrate synthase had declined, and strength was 10 to 20 percent lower.
What this means for you: For your mitochondria, inactivity is not idling, but a signal of its own. It says: "Break down."
Abadi A et al. Limb immobilization induces a coordinate down-regulation of mitochondrial and other metabolic pathways in men and women. PLoS One. 2009;4(8):e6518. DOI: 10.1371/journal.pone.0006518Here the circle closes to metabolism. Kelley and colleagues from Pittsburgh compared the respiratory chain in the muscle of lean people, people with obesity and people with type 2 diabetes. Activity was highest in lean people and lowest in type 2 diabetes, and the mitochondria were smaller in obesity and diabetes. Whether this is cause or consequence of insulin resistance is still debated today.
The KPNI perspective: energy for four systems
From the perspective of KPNI (Clinical Psychoneuroimmunology), mitochondria are not just muscle batteries. Every major regulatory system in your body depends on their performance.
Metabolism
Capable mitochondria can burn sugar and fat flexibly. If their capacity drops, more sugar might remain in the blood and fat might accumulate in liver and muscle. This fits the findings in insulin resistance.
Immune system
Immune cells need a lot of energy to respond and then calm down again. Stressed mitochondria release more reactive oxygen species, which can fuel silent inflammation. Mechanistically plausible, not yet fully understood in humans.
Nervous system
Your brain uses around one fifth of your energy, even though it makes up only a small part of your weight. Concentration, mood and resilience also depend on the energy supply of nerve cells.
Hormonal system
The production of steroid hormones, such as cortisol and sex hormones, begins in the mitochondria. Thyroid hormones, in turn, help regulate how actively the power plants work. Energy and hormones are closely intertwined.
Supported by human studies: training can increase the content and function of muscle mitochondria, and inactivity can reduce them rapidly. Mechanistically plausible, but still thin in humans: that direct effects on the immune system, brain and hormonal balance can be derived from this. Clinically, I observe that people who move regularly often report more stable energy. That is experience, not a study.
Lack of movement is not just the absence of exercise. It is an active command to your cells to reduce capacity. The good news lies in the same sentence: what responds so quickly to standstill also responds to movement.
And now you know why even a few days on the couch can be noticeable, and why getting back into it is still worthwhile. You can read how to break up sitting time in everyday life in the article Sitting and lack of movement.
Three levers for your power plants
You don't need a lab or a training plan from a sports magazine. You need a direction that fits your life. What follows are principles drawn from the evidence, not recipes.
A calm foundation
Regular endurance at a pace where you can still talk builds volume without a large recovery burden. According to reviews, volume in particular appears to drive mitochondrial content. Brisk walking, cycling or swimming all count.
Targeted intensity
Short, demanding segments send a strong building signal to PGC-1α and the respiratory chain. They can be added sparingly when your body is resilient enough. With cardiovascular disease or severe exhaustion, starting out should involve a medical check-up.
Less standstill
Inactivity sends its own breakdown signal, after just a few days. Break up long periods of sitting, walk where you can and take the stairs. Consistency over months beats one big heroic effort.
Adaptation does not happen during training, but in the recovery afterwards. Sleep, sufficient protein and micronutrients such as iron, which the respiratory chain needs, form the foundation. Whether you have a deficiency can be clarified in the lab, not by guessing.
If you feel persistently exhausted despite training, more load is not automatically the answer. Then a closer look is worthwhile, for example in the article Exercise and chronic exhaustion.
Energy is not a luxury that some people simply have. Energy is something your cells produce every day. And they produce more when you ask them to.
This is about more than citrate synthase and the respiratory chain. It is about still joining your grandchildren on a mountain hike at 70. About still feeling like doing something after a day at work. About your body following you instead of holding you back. In this sense, energy is freedom.
And now you know why movement may be the most direct conversation you can have with your cells.
Frequently asked questions about mitochondria and exercise
Can I really strengthen my mitochondria through exercise?
The evidence here is unusually clear. Endurance and interval training are among the best studied stimuli for building new mitochondria in muscle, a process called mitochondrial biogenesis.
In training studies with muscle biopsies, mitochondrial content, respiratory capacity or both increased, depending on the program. How strong the effect is for you depends on your starting point, age, type of training and consistency.
What is better for mitochondria: HIIT or easy endurance training?
Both can work, but in different ways. In a single-leg cycling study, interval training led to larger increases in citrate synthase activity and mitochondrial respiration than continuous training at the same total work.
Reviews suggest that intensity mainly influences respiratory function, while training volume tends to determine mitochondrial content. A combination of both therefore appears sensible.
What is PGC-1α and why does it matter so much?
PGC-1α is a protein that, like a construction manager, coordinates many genes needed to build new mitochondria. A Danish study found a 10 to over 40-fold increase in PGC-1α gene expression in human muscle after exercise, peaking within two hours.
Each training session is therefore a short, strong signal. Only repetition over weeks turns it into a lasting remodeling.
Do we inevitably lose mitochondria as we age?
On average, mitochondrial performance declines with age. In a study of 146 people aged 18 to 89, mitochondrial DNA and ATP production decreased with increasing age.
Another study, however, found that active older adults had a mitochondrial capacity similar to active young adults, while inactive older adults were clearly lower. Part of the apparent aging effect may therefore be an activity effect.
Am I too old at 65 or 70 to train my mitochondria?
The available data suggest otherwise. In a training study of people around 67 years old, muscle mitochondrial DNA rose from about 1264 to 1895 copies, and respiratory chain activity roughly doubled.
In a twelve-week Mayo Clinic study, interval training appeared to reduce many age-related differences in muscle proteins in older adults. If you have pre-existing conditions, a medical check-up before starting intensive training is advisable.
Does strength training also strengthen mitochondria?
The data are mixed. In an Innsbruck study of 25 inactive adults, both endurance and strength training increased the ability of mitochondria to burn fat over ten weeks, by 2.6-fold and 2.4-fold respectively.
In the Mayo Clinic study, on the other hand, strength training alone did not improve mitochondrial respiration, while interval and combined training did. Strength training is valuable for muscle mass and insulin sensitivity; for mitochondria, an endurance component appears to be the stronger stimulus.
How quickly do I lose mitochondria if I don't move?
Surprisingly quickly. In a Canadian study, one leg of 24 healthy adults was immobilized for two weeks. After just 48 hours, genes for mitochondrial energy production were expressed less, and after 14 days the activities of the enzymes cytochrome c oxidase and citrate synthase declined.
For mitochondria, inactivity is therefore not a neutral state but a stimulus of its own in the wrong direction.
What do mitochondria have to do with insulin resistance and diabetes?
Muscle mitochondria burn sugar and fat. A study from Pittsburgh found the lowest respiratory chain activity in muscle in people with type 2 diabetes and the highest in lean people, with people with obesity in between. The mitochondria were also smaller in diabetes and obesity.
Whether this is cause or consequence is still debated. Training, however, appears to be able to act at both ends.
What does Zone 2 training have to do with mitochondria?
Zone 2 describes a calm endurance intensity at which the body burns a lot of fat and accumulates little lactate. A study by San-Millán and Brooks showed that fat oxidation and blood lactate are closely and inversely related across very different people.
Both are considered an indirect window into mitochondrial capacity. Direct comparative studies on Zone 2 as a training form of its own, however, are still scarce.
How much time do I need for my mitochondria to change?
First adaptations can appear within a few weeks. In a Canadian study, the oxidative capacity of muscle increased after just six sessions in two weeks, both with short sprint intervals totaling about 2.5 hours and with classic endurance training totaling about 10.5 hours.
Lasting changes, however, require consistency over months. If volume and stimuli are reduced, the adaptations can recede.
Keep reading on the ViveCura Blog
Understanding Zone 2 training
The calm pace and your fat metabolism.
ExerciseImproving VO2max
Why endurance fitness says so much about life expectancy.
ExerciseExercise as medicine
What training can set in motion at the cellular level.
ExerciseRecovery is not doing nothing
Why adaptation happens during recovery.
SleepSleep, hormones and recovery
Why the night helps decide the training effect.
MetabolismFatty liver: what to do?
When energy builds up in the liver.
Sources
All studies were checked against PubMed; figures are taken from the respective abstracts. Many mitochondrial studies are small and work with muscle biopsies in young, healthy men. Cross-sectional studies show associations, not cause and effect. This is noted in the text. This article does not replace a medical examination or individual training advice.
- Robinson MM, Dasari S, Konopka AR, Johnson ML, Manjunatha S, Esponda RR, Carter RE, Lanza IR, Nair KS. Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans. Cell Metab. 2017;25(3):581-592. DOI: 10.1016/j.cmet.2017.02.009 [Clinical training study over 12 weeks, younger and older adults]
- MacInnis MJ, Zacharewicz E, Martin BJ, Haikalis ME, Skelly LE, Tarnopolsky MA, Murphy RM, Gibala MJ. Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work. J Physiol. 2017;595(9):2955-2968. DOI: 10.1113/JP272570 [RCT, within-subject design, n=10]
- Granata C, Oliveira RS, Little JP, Renner K, Bishop DJ. Training intensity modulates changes in PGC-1α and p53 protein content and mitochondrial respiration, but not markers of mitochondrial content in human skeletal muscle. FASEB J. 2016;30(2):959-70. DOI: 10.1096/fj.15-276907 [RCT, n=29]
- Gibala MJ, Little JP, van Essen M, Wilkin GP, Burgomaster KA, Safdar A, Raha S, Tarnopolsky MA. Short-term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance. J Physiol. 2006;575(Pt 3):901-11. DOI: 10.1113/jphysiol.2006.112094 [Pathophysiology, controlled training study with muscle biopsies, n=16]
- MacInnis MJ, Gibala MJ. Physiological adaptations to interval training and the role of exercise intensity. J Physiol. 2017;595(9):2915-2930. DOI: 10.1113/JP273196 [Review]
- Granata C, Jamnick NA, Bishop DJ. Training-Induced Changes in Mitochondrial Content and Respiratory Function in Human Skeletal Muscle. Sports Med. 2018;48(8):1809-1828. DOI: 10.1007/s40279-018-0936-y [Review]
- Granata C, Jamnick NA, Bishop DJ. Principles of Exercise Prescription, and How They Influence Exercise-Induced Changes of Transcription Factors and Other Regulators of Mitochondrial Biogenesis. Sports Med. 2018;48(7):1541-1559. DOI: 10.1007/s40279-018-0894-4 [Review]
- Pilegaard H, Saltin B, Neufer PD. Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. J Physiol. 2003;546(Pt 3):851-8. DOI: 10.1113/jphysiol.2002.034850 [Pathophysiology, human study with muscle biopsies, n=7]
- Little JP, Safdar A, Bishop D, Tarnopolsky MA, Gibala MJ. An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1α and activates mitochondrial biogenesis in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2011;300(6):R1303-10. DOI: 10.1152/ajpregu.00538.2010 [Pathophysiology, human study with muscle biopsies, n=8]
- Pesta D, Hoppel F, Macek C, Messner H, Faulhaber M, Kobel C, Parson W, Burtscher M, Schocke M, Gnaiger E. Similar qualitative and quantitative changes of mitochondrial respiration following strength and endurance training in normoxia and hypoxia in sedentary humans. Am J Physiol Regul Integr Comp Physiol. 2011;301(4):R1078-87. DOI: 10.1152/ajpregu.00285.2011 [Pathophysiology, comparative training study, n=25]
- Short KR, Bigelow ML, Kahl J, Singh R, Coenen-Schimke J, Raghavakaimal S, Nair KS. Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci U S A. 2005;102(15):5618-23. DOI: 10.1073/pnas.0501559102 [Real-world, cross-sectional, n=146]
- Distefano G, Standley RA, Zhang X, Carnero EA, Yi F, Cornnell HH, Coen PM. Physical activity unveils the relationship between mitochondrial energetics, muscle quality, and physical function in older adults. J Cachexia Sarcopenia Muscle. 2018;9(2):279-294. DOI: 10.1002/jcsm.12272 [Real-world, cross-sectional, n=39]
- Menshikova EV, Ritov VB, Fairfull L, Ferrell RE, Kelley DE, Goodpaster BH. Effects of exercise on mitochondrial content and function in aging human skeletal muscle. J Gerontol A Biol Sci Med Sci. 2006;61(6):534-40. DOI: 10.1093/gerona/61.6.534 [Pathophysiology, intervention study without control group, n=8]
- Abadi A, Glover EI, Isfort RJ, Raha S, Safdar A, Yasuda N, Kaczor JJ, Melov S, Hubbard A, Qu X, Phillips SM, Tarnopolsky M. Limb immobilization induces a coordinate down-regulation of mitochondrial and other metabolic pathways in men and women. PLoS One. 2009;4(8):e6518. DOI: 10.1371/journal.pone.0006518 [Pathophysiology, immobilization study, n=24]
- Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes. 2002;51(10):2944-50. DOI: 10.2337/diabetes.51.10.2944 [Real-world, cross-sectional, n=30]
- San-Millán I, Brooks GA. Assessment of Metabolic Flexibility by Means of Measuring Blood Lactate, Fat, and Carbohydrate Oxidation Responses to Exercise in Professional Endurance Athletes and Less-Fit Individuals. Sports Med. 2018;48(2):467-479. DOI: 10.1007/s40279-017-0751-x [Real-world, cross-sectional, professional athletes, active individuals and metabolic syndrome]