The guest that stayed

What they are

Mitochondria are small structures inside nearly every one of your cells. Each one is wrapped in two membranes. The outer one is smooth. The inner one is folded over and over into ridges called cristae, which pack a large working surface into a small space. On that inner membrane sits a chain of protein complexes that turns food and oxygen into ATP, the molecule every cell spends as energy.

The numbers vary a lot by tissue. A red blood cell has none. A liver cell may hold a thousand or more. In heart muscle, which never rests, mitochondria take up roughly a third of each cell. They aren't fixed objects either. They fuse, split, move along the cell's internal scaffolding, and get recycled when they wear out.

Where they came from

Mitochondria are the descendants of bacteria. Somewhere around two billion years ago, a single-celled host (most likely related to today's Asgard archaea) took in a bacterium related to modern alphaproteobacteria. The bacterium wasn't digested, it kept living inside its host. The partnership worked, and every animal, plant and fungus alive today descends from it.

1. ~2 bn yrs agoA bacterium that can burn fuel with oxygen ends up living inside a host cell. The host gets energy, and the guest gets shelter and food.
2. Over agesMost of the guest's genes move to the host's nucleus or disappear. The guest can't live on its own anymore. It's become an organelle.
3. 1967Biologist Lynn Margulis sets out the endosymbiosis theory. It's widely doubted at first.
4. 1970s–80sGene sequencing confirms it. Mitochondrial DNA and ribosomes look bacterial, not like the rest of the cell.

The bacterial past still shows. Mitochondria have their own circular DNA and their own ribosomes, which resemble a bacterium's closely enough that some antibiotics can affect them. Their inner membrane contains cardiolipin, a fat otherwise found in bacteria. They multiply by dividing, the way bacteria do. And you inherit them only from your mother, because the egg carries the mitochondria into the next generation and the sperm's are discarded.

Why they're in your cells

Burning fuel with oxygen releases far more energy than the older, oxygen-free routes cells relied on. From one glucose molecule, the oxygen route yields many times more ATP than fermentation alone. Some biologists, Nick Lane among them, argue this is the reason complex life exists at all. Spreading energy production across hundreds of small power stations, each with a few local genes to manage it, let a cell afford a far larger genome and a far more complicated body. Bacteria never made that leap, and cells with mitochondria did.

Every complex cell alive today is a partnership that began with one host that didn't digest its meal.

What they do

Their main job is energy. Electrons stripped from food are handed to a carrier called NAD+ (it becomes NADH), which delivers them to the chain of complexes on the inner membrane. As electrons pass down the chain to oxygen, the complexes pump protons across the membrane, building up a charge like water behind a dam. The last machine, ATP synthase, lets the protons flow back through it and spins as they do, making ATP.

That isn't all they do:

• Signalling. Mitochondria tell the rest of the cell how energy is going, partly through small amounts of reactive oxygen species and partly through peptides they encode themselves, such as MOTS-c.
• Deciding when a cell dies. Releasing a protein called cytochrome c from the mitochondria is a key step in programmed cell death, which removes damaged cells.
• Calcium. They buffer calcium, which every muscle contraction and nerve signal depends on.
• Building blocks. The first steps of making steroid hormones (including testosterone and cortisol) and of making haem, the iron-holding part of haemoglobin, happen inside them.
• Heat. In brown fat, mitochondria deliberately leak their proton charge to produce heat instead of ATP.

What happens with age

Mitochondria don't simply wear out on a schedule, but several things tend to drift with the years, and they feed each other:

• Leaks. A small share of electrons escape the chain and form reactive oxygen species. In small amounts these are useful signals. In excess they damage membranes, proteins and mitochondrial DNA, which sits right next to where they're made and has fewer repair systems than the nucleus.
• Mutations pile up. Damaged copies of mitochondrial DNA accumulate, unevenly, in long-lived tissues such as muscle and brain.
• Less renewal. Cells make fewer new mitochondria (a process called biogenesis, run largely by a master switch called PGC-1α), and get worse at clearing out damaged ones (mitophagy). Old, inefficient mitochondria linger.
• NAD+ falls. Levels of NAD+ decline in several tissues with age. That matters twice, because it carries electrons into the chain, and the sirtuin enzymes that maintain mitochondria need it to work.
• Inactivity makes it worse. Much of what looks like ageing in muscle mitochondria tracks with how much people move. Active older adults often have mitochondrial capacity closer to younger people than to inactive peers.

What that means for health

When energy supply falls behind demand, the tissues that need the most energy show it first. The links below are well established as associations. How much of each is caused by mitochondria, and how much mitochondria are a casualty of something else, is still being worked out.

• Fitness and fatigue. Aerobic capacity (VO2 max) typically drops around 10% per decade after 30 in people who don't train, and lower capacity is one of the strongest predictors of mortality.
• Muscle loss. Mitochondrial decline is tied to sarcopenia, the slow loss of muscle mass and strength.
• Blood sugar. Muscle with fewer or poorer mitochondria clears glucose less well, which is part of the path to insulin resistance and type 2 diabetes.
• Heart. Heart muscle depends on a constant energy supply, and impaired mitochondrial energetics is a feature of heart failure.
• Brain. Several genes behind inherited Parkinson's disease are mitochondrial maintenance genes, and energy failure appears in other neurodegenerative conditions too.
• Inflammation. Fragments of damaged mitochondria look bacterial to the immune system. When they escape the cell they can set off low-grade inflammation, one contributor to what researchers call "inflammaging".

What helps them

I've labelled each option below for how good the human evidence is. The labels are a summary, not a verdict on any individual.

Exercise Strong

Nothing else comes close. Endurance training increases both the number and the quality of mitochondria in trained muscle, in young and old people alike. Steady, easy work you can sustain for a long time (often called zone 2) builds the base, short hard intervals add a strong signal of their own, and strength training keeps the muscle that houses the mitochondria. The effect fades within weeks of stopping, so consistency matters more than any single session.

Sleep Moderate

Short or broken sleep worsens insulin sensitivity within days, and sleep is when a lot of repair and recycling happens. Breathing problems at night deserve particular attention, because repeated drops in oxygen put the whole energy system under stress.

Not overfeeding, and eating enough protein Moderate

A chronic surplus of energy, especially alongside inactivity, clogs mitochondria with more fuel than they can use, which raises leakage. Losing excess weight improves mitochondrial function in muscle. Calorie restriction and time-restricted eating show clearer mitochondrial benefits in animals than in people so far. Enough protein protects the muscle mass the mitochondria live in.

Alcohol and smoking Strong

Alcohol is processed partly in mitochondria and directly damages them, including the cardiolipin in their inner membranes. Smoking delivers carbon monoxide and other toxins that block the chain itself. Cutting back is one of the clearest wins available.

Heat and cold Early

Regular cold exposure recruits brown fat and its heat-making mitochondria, and sauna use triggers heat-shock proteins that help other proteins keep their shape. Both have plausible mechanisms and some human data, but much less than exercise.

Outside help

This is where marketing runs furthest ahead of evidence. None of the options below substitutes for the ones above, and several interact with medications. I'm deliberately not giving doses in this guide.

Red and near-infrared light Early

One component of the mitochondrial chain, cytochrome c oxidase, absorbs red and near-infrared light. The idea behind photobiomodulation is that light at those wavelengths nudges the chain to work better. Small studies report effects on muscle recovery, skin and some measures of eyesight in older adults, though not every result has been reproduced. Devices differ enormously in wavelength and power, which makes results hard to compare and home panels hard to judge.

NAD+ and its precursors Moderate

Precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) reliably raise NAD+ levels in blood. Whether that turns into better function is less clear. Human trials have mostly been small and short, with modest or inconsistent results on muscle, blood sugar and blood pressure. Injected NAD+ is popular in clinics, but it has even less controlled data behind it. My NAD guide goes through the pills and the injections in detail.

SS-31 (elamipretide) Early

A small peptide that settles into the inner mitochondrial membrane and binds cardiolipin, with the aim of keeping the energy chain's proteins in shape so it leaks less. It's one of the few mitochondria-targeted drugs to reach late-stage trials. It was approved in the US in 2025 for Barth syndrome, a rare inherited mitochondrial disease. Trials in more common conditions, including heart failure and adult mitochondrial muscle disease, have so far been mixed or missed their main goals. Clinical trials used doses well above those circulating in peptide communities, and there's no good evidence that a short course has lasting effects.

MOTS-c Mostly animal

A peptide encoded in mitochondrial DNA itself, discovered in 2015. In mice it acts like an exercise signal: it switches on AMPK, the cell's fuel gauge, improves insulin sensitivity and increases exercise capacity. Levels in the body appear to fall with age. Human evidence is very thin, and the cycles sold online come from community practice, not from studies.

Coenzyme Q10 Moderate

A component of the energy chain that the body makes itself. Statin medications reduce how much the body makes, which is why it's often suggested to people on statins, but trials for statin-related muscle aches are mixed. A trial in heart failure was encouraging. For healthy people with normal levels, the benefits are unproven.

Urolithin A Early

Gut bacteria make it from compounds in pomegranates and some nuts, and it's now sold as a supplement. It appears to switch on mitophagy, the clearing out of damaged mitochondria. A handful of human trials in middle-aged and older adults reported improvements in some measures of muscle endurance.

Creatine Strong

Not a mitochondrial treatment exactly, but closely related. Creatine acts as a quick energy buffer that shuttles energy from mitochondria to where it's spent. Its benefits for strength and muscle, especially alongside training, are among the best-supported of any supplement.

Medications with mitochondrial effects Moderate

Some common drugs act on mitochondria, for better or worse. Metformin works partly by mildly inhibiting the chain, and in some trials it blunted the gains older adults made from training. GLP-1 medicines change how much fuel reaches mitochondria by changing how much people eat. If you're on these, or considering mitochondria-targeted products, go through them with your doctor.

The short version

Mitochondria are a two-billion-year-old partnership that made complex life possible. They decline with age, but a lot of that decline follows inactivity, excess fuel, alcohol and poor sleep, and you can change all of those. Exercise is the most powerful tool by a wide margin. Outside help ranges from well supported (creatine) to promising (urolithin A, light, NAD+ precursors) to largely untested in people (MOTS-c). If you try something, decide in advance what you'd expect to change (blood sugar, heart rate at the same effort, energy), and measure it against your own normal range.

This guide explains the science in general terms. It isn't medical advice and it gives no doses. Talk to your doctor before starting anything here, especially if you have a heart rhythm condition or take regular medication.