MOTS-c and SS-31 — mitochondrial, but almost opposite evidentiary situations

Both sold on mitochondrial function, both in the longevity bucket, and their pages could not be more different. MOTS-c is research / evidence: none. SS-31 is approved / evidence: mixed.

Worth putting side by side.

Very much worth it, and the contrast teaches something.

MOTS-c has the more remarkable biology. It is encoded by mitochondrial DNA rather than the nucleus, which almost nothing is — that alone is a genuinely interesting discovery. Blood levels rise with exercise, which is one of the better-replicated findings about it, and levels differ between metabolically healthy and unhealthy people.

But notice what all of that is: it is observational biology about an endogenous molecule. "Levels rise with exercise" tells you it is part of the response. It does not tell you that injecting it produces the response. That inference — biomarker to intervention — is one of the most reliably wrong moves in the whole of medicine. It is the reasoning that produced hormone replacement for prevention and antioxidant supplements for longevity, and both of those went the way they went in trials.

SS-31 is the opposite shape. Narrow, mechanistically precise — it binds cardiolipin, a lipid that exists nowhere in the cell except the inner mitochondrial membrane, so it accumulates exactly where it is meant to act. And it got approved, in 2025, for Barth syndrome.

And the SS-31 approval is a beautiful illustration of how narrow an approval can be.

Barth syndrome is a rare genetic disorder involving a defect in cardiolipin. The drug binds cardiolipin. The match between mechanism and disease is about as tight as it gets.

That is what the approval is evidence for. It is not evidence for fatigue in a healthy adult, or exercise capacity, or ageing. Those are the marketed uses and they carry the mixed label, correctly.

"Approved medicine" is again being used to import confidence across an indication boundary.

So MOTS-c: fascinating biology, zero human intervention evidence, and a biomarker-to-intervention leap. SS-31: real approval, precisely matched to a rare disease, marketed for something else entirely.

Both are sold to the same people for the same reason.

The exercise-mimetic framing on MOTS-c deserves one more kick. If a molecule rises when you exercise, the intervention with the overwhelming evidence base is the exercise.

Free, too.