Pillar 03
The cell's power plants produce less energy than they used to. The tissues that need the most energy feel it first.
| Test | What it measures | The number | What it misses |
|---|---|---|---|
| VO2max on a proper exercise test | The most oxygen you can use per minute, on a treadmill or bike with a mask on. The closest thing to a whole-body readout. | Compared against age and sex percentiles from the FRIEND registry, the US reference set. There is no dysfunction threshold, only where you sit in the distribution. | It measures the whole chain: heart, lungs, blood, muscle. A low number does not tell you which link is weak. |
| Blood lactate | Lactate builds up when energy production falls back on its less efficient route. | The Mitochondrial Medicine Society's 2015 consensus names above 3 mmol/L, properly collected, as markedly elevated (PMID 25503498). | Set for diagnosing inherited mitochondrial disease, not ageing. A struggling tourniquet or a clenched fist during the draw will raise it on its own. |
| GDF-15 and FGF-21 | Stress signals that cells release when their energy machinery is in trouble. The best blood markers available. | No agreed cut-off. Published studies picked different ones. | Their accuracy figures come from patients with diagnosed mitochondrial disease. What they mean in a healthy person is not established. |
| ATPmax by magnetic resonance spectroscopy | How fast muscle rebuilds its energy currency after exercise, measured in a scanner without a needle. | No threshold set by any body. A research measure. | Requires a research MRI facility. Not orderable. |
| Muscle biopsy | Enzyme activity measured directly in muscle tissue. | The reference standard for diagnosis, recommended for suspected inherited disease (PMID 25503498). | It is a surgical sample, for a diagnostic question you almost certainly do not have. |
| Blood NAD+, mitochondrial DNA copy number | Consumer-adjacent tests sold as mitochondrial readouts. | Neither has a reference range set by any guideline body that I could find. | Copy number in blood shifts with which white blood cells happen to be in the tube, which is a confounder before it is a signal. |
The free radical story failed its most direct test. The idea that ageing is oxidative damage, so antioxidants should slow it, is the mechanism everyone repeats. One laboratory spent years raising and lowering eighteen separate antioxidant genes in mice and did not get the lifespan changes the theory predicts. The mechanism is still taught. The intervention built on it did not work.
"NAD+ falls with age, so top it back up" does not survive careful measurement. The premise is that whole-blood NAD+ declines as you get older. The largest and most carefully validated measurements across multiple human cohorts do not find that decline. The supplement category is considerably more confident than the measurement it rests on.
Feeling tired is not a readout of your mitochondria. This is the inference the whole consumer category rests on, and the human evidence tying measured muscle energetics to how tired someone feels is weak. Fatigue has many more common explanations, and every one of them is easier to check.
8 compounds covered here are marketed or taken on this rationale. Each entry says where its dose came from and what the published record supports, which is usually less than the pitch.
The mice really did run about 70 percent longer, and the people who made the compound have written in print that it does not get from the gut into the blood.
The trial programme is real, large and mostly failed. For once the dose people run sits below what was studied rather than above it.
The word lifespan in that title is carried by worms, and most of the rest of the record belongs to a mutant version of the peptide rather than the one sold in vials.
Roughly 7,100 people were randomised and about 3,550 got the drug, all in heart surgery, and three separate infusion studies failed to move the enzyme it is sold for.
Mouse dosing stopped at 200 mg per kilogram because the compound would not dissolve any further, so what the record holds is a formulation limit rather than a safety ceiling.
It is sold as a peptide and it is not one. I could not find a published human study, and the NAD+ rise and the fat loss were never measured in the same organism.
I could find no study giving MOTS-c to a human. The one registry record saying otherwise was forged, and unlike its siblings it does not confess.
Enzymes on the outside of the cell take NAD+ apart before anything crosses the membrane, and only the fragments go in. Which leaves the drip as a delivery system for precursors, sold on evidence generated by swallowing precursors.
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