Oh that’s great and reassuring to see and is a brand new study published after this thread was started, thanks for sharing!
But, the other thing to be potentially concerned about is the genetic variant (which appear all too common) that increases ergothioneine uptake into tissues and could make it potentially harmful if supplemented in large amounts.
I injected 20 mg x 10 days + 10 mg x 15 days of SS-31. I did not notice anything. An optimistic hypothesis is that my mitochondria are in too good condition to make any effect noticeable. I missed making any tests.
I might consider another try. 40 mg per day as per the dose for Barth and simultaneously taking intranasal Orexin-A on the possibility that a lack of this could prevent effects of SS-31, as detailed in the thread on Orexin.
You might be right.
I would think at the doses you have tried that your conclusion is correct. Your mitochondria are likely healthy and probably won’t benefit from going even higher.
To be honest, I find that hard to believe. Is it even possible for anyone over the age of 65 or 70 (Ulf, I forget how old you are exactly) to not have significantly degraded mitochondria? Ulf, no doubt about, you are in great shape and doing well (much better than most people your age, or even much younger).
But… I would still think that even for people in good shape the mitochondria would be significantly degraded, and if their cardiolipin membranes were returned to functional youth, that you’d feel a significant benefit.
I wonder if the dose might be too low? Or perhaps there is a “wrong order” in the peptide delivered?
See this type of research, which is part of my thinking: Rust Never Sleeps: Why Your Mitochondria May Be Running on Half-Empty Vitamin Tanks by Age 50
Nothing in that article about cardiolipin.
Since SS 31 only does 1 thing, it is quite possible that the 1 thing is not an issue for aged people whole live a healthy lifestyle… and there are many other aspects of mito disfunction besides the cardiolipin layer that SS 31 cannot fix as outlined in the article referenced.
Researchers at Imperial College London report that SS-31 (elamipretide), a four amino acid peptide already approved by the FDA for the ultra-rare mitochondrial disease Barth syndrome, competes directly with alpha-synuclein for space on negatively charged lipid membranes. Using single-molecule fluorescence methods, the team showed SS-31 strips alpha-synuclein off synthetic synaptic-like vesicles at sub-stoichiometric concentrations, slows and blunts lipid-triggered amyloid fibril formation, reduces uptake of toxic alpha-synuclein oligomers into neuroblastoma cells, and partially restores mitochondrial respiration and cell viability in cells poisoned with those oligomers. The work is entirely test-tube and cell culture based, with no animal or human data, and the authors themselves caution that the mitochondrial rescue may reflect a generic mitochondrial benefit rather than anything specific to alpha-synuclein.
Parkinson’s disease is defined by clumps of a protein called alpha-synuclein. What is less widely appreciated is that this protein does not misfold in a vacuum. It normally binds to the fatty membranes of synaptic vesicles, and that binding is precisely what kickstarts the misfolding. Membrane contact forces the floppy, unstructured protein into a partly helical shape that acts as a seed for the beta-sheet aggregates that go on to kill dopamine neurons. Block the binding and you may block the seeding.
That is the big idea this paper tests, and the tool it uses is unusual. SS-31, also called elamipretide, is a synthetic tetrapeptide that has spent two decades being developed as a mitochondrial drug. It carries a net positive charge and homes in on cardiolipin, a negatively charged lipid concentrated in the inner mitochondrial membrane, where it improves electron transport and mops up reactive oxygen. In September 2025 it became the first drug approved specifically to target mitochondria, for Barth syndrome.
The Imperial team reasoned that a positively charged peptide with a taste for anionic lipids ought to compete with alpha-synuclein, which anchors to membranes through its positively charged N-terminal region binding the same negative surfaces. It does. Fluorescence anisotropy and fluorescence correlation spectroscopy both showed SS-31 displacing alpha-synuclein from model vesicles in a dose-dependent way, with half-maximal displacement at roughly a 0.7 to 1 peptide to protein ratio. Circular dichroism confirmed the displaced protein loses its membrane-induced helical structure.
Downstream, the consequences look useful. Lipid-accelerated fibril formation was delayed by tens of hours and reduced in amount. Electron microscopy showed altered fibril architecture. In human neuroblastoma cells, SS-31 cut internalisation of alpha-synuclein oligomers by up to half, and restored basal and maximal mitochondrial respiration that the oligomers had suppressed.
The caveats are substantial. This is a mechanism paper, not an efficacy paper. Everything happens in artificial vesicles or immortalised cancer-derived cell lines. Above 100 micromolar, SS-31 itself became toxic. And SS-31 improved cell health even without alpha-synuclein present, which makes it hard to separate a specific anti-synuclein effect from a general mitochondrial tonic. Still, it is a plausible new mechanism for a drug already in humans, which is a shorter path than most.
This is a chemistry and cell culture study with no animals, no patients, no dosing, and no lifespan data.
What the numbers do say, translated: in cells poisoned with alpha-synuclein oligomers, viability fell from 100 to about 46 percent. Adding the best dose of SS-31 lifted it to about 60 percent. In plain terms the peptide recovered roughly a quarter of what was lost, an effect size of about 0.8 standard deviations, which counts as moderate to large but is nowhere near a rescue. Mitochondrial respiration recovered more convincingly, with effect sizes near 1.8 to 2.1 standard deviations, meaning the treated and untreated groups barely overlap.
The transferable idea is that membrane lipid composition is upstream of protein aggregation. Anything that alters synaptic membrane charge and fluidity is a legitimate target class. Watch this space rather than acting on it.
SS-31 ADHD connection
Interesting. Do we have PK studies? To know more about the perfect dosage ? And make sure we are well below the 100uM 
Not sure PK would tell us a “perfect” dose as we all respond to things a bit differently.
Not sure a perfect dose is required but an adequate dose that would be higher than the perfect dose is most likely required. Low dose has been studied and indicated no benefit for mito’s and very high doses have been studied in humans with no issues and greater benefit
From what I’ve read since I started taking SS 31 is that anything less than 5.0 mg per dose is close to useless for mitos and that higher doses have a better result.
People can easily tolerate 60.0 mg daily doses for extended periods of time. The prescribed dose for Barths is 40.0mg per day for the rest of their lives.
I do 10mg per day for 10 days 2 months on, 1 month off.
BUT I started with 10.0mg twice a day (20mg) for 10 days to get closer to what is used in the published human studies.
Test tubes are great but humans are the gold standard
SS 31 - elamipretide, provide mechanistics, clinic.pdf (1.3 MB)
That’s very interesting.
Tremendous fatigue, I have been using it for 2 months now and cant get past 1mg. I have to take a nap if I take it, it just wipes me out.
This thread goes to the heart of the matter. Taking my own case, can a 79-year old with an optimal life-style entirely prevent significant mitochondrial degeneration?
Unfortunately, I have to agree with rapadmin that the answer is no. Long interaction with my ai resulted in the summary “Regular lifelong exercise can substantially preserve—and sometimes make selected muscle-mitochondrial measures comparable with those of younger, equally active people—but it does not eliminate all intrinsic biological aging” (from mitochondrial degeneration)”
It´s not an even deterioration. Many mitochondrial measures are preserved entirely with exercise, others only partially or not at all. The new Dutch study showed that exercise prevented 55.9% of normal age-related gene upregulations and 57.1% of age-related gene downregulation, with the remaining 43-44% not prevented. What I can glean from studies is that among the decline in mitochondrial adaptations with exercise may be a deterioration in stress-induced signaling kinase activation. Accumulated mtDNA damage/deletions in some fibres, altered mitochondrial morphology, impaired mitophagy/autophagy, motor-neuron loss, and lower regenerative capacity may occur despite exercise.
What to do? With 20 mg SS-31 not making a difference in my loss of energy - needing a break after 4-5 hours of work instead of ten hours non-stop 15 years ago - I would like to try SS-31 at 40 mg per the Barth protocol. And continue with low-intensity near-daily exercise, intensive resistance training and sprint interval training. The major prevention of mitochondrial deterioration not only targets skeletal muscle but likely also all other organs.
| Organ | What exercise likely does | Strength of conclusion |
|---|---|---|
| Skeletal muscle | Increases oxidative capacity and mitochondrial content; supports mitochondrial turnover, dynamics, and quality-control signalling | Strong direct human evidence |
| Heart | Supports mitochondrial respiration, redox defence, calcium handling, and turnover; benefits occur alongside improved vascular and metabolic conditions | Strong biological rationale and substantial animal evidence; more limited direct healthy-human tissue data |
| Liver | Improves lipid handling, insulin sensitivity, oxidative metabolism, and likely mitochondrial stress/quality control—particularly when liver fat or insulin resistance are present | Good human metabolic evidence; direct mitochondrial-quality-control evidence is less extensive |
| Brain | Exercise plausibly supports neuronal mitochondrial function through improved cerebral blood flow, lower inflammation, neurotrophic signalling such as BDNF, and redox defences | Human functional evidence is strong, but direct evidence of neuronal mitophagy/biogenesis in living people is limited |
| Kidney | Exercise may improve vascular/metabolic conditions and reduce oxidative and inflammatory stress that affect renal mitochondria | Mostly preclinical; evidence in healthy aging humans is modest |
| Immune cells | Appropriate regular activity can improve immunometabolic flexibility and lessen chronic inflammatory signalling, indirectly reducing mitochondrial stress | Promising, but still less direct than muscle evidence |
A mitochondrial “autograft”? (paywalled)
Patient’s own mitochondria injected into eyes in attempt to restore vision
More info here also: A first-in-human case explores whether viable autologous mitochondria can be delivered directly into the eye to rescue injured but still living neurons.
Full (non-paywalled article) from above post:
Scientists have extracted mitochondria from a woman’s leg muscles and injected them into the vitreous fluid of her eyes in an attempt to treat severe blindness. The procedure caused no inflammation or side effects — but had a limited effect on restoring responses to light in the eyes, and did not restore the woman’s vision.
Transplanting healthy mitochondria — organelles that produce energy in cells — is being explored as a way to treat diseases that damage these organelles in tissues. The healthy mitochondria can be taken up by the damaged cells and, in some cases, boost cell survival and partially restore tissue functions. Previous trials in humans have transplanted mitochondria into the heart and brain. Now, scientists report the first such transplant in the eyes.
A brain bleed in February had injured the woman’s optic nerve and retina, causing nearly complete blindness, with no pupil responses to light flashed in her eyes. After the mitochondrial injections, her pupils showed a response to light, but the effect was temporary and subsided after about four weeks. The findings were reported in a preprint posted on 10 August, which has not been peer reviewed1.
The study shows that it was “relatively safe” to inject the person’s own mitochondria into the eyes, says Temurkhan Ayupov, a mitochondria biologist at the Institute of Molecular and Clinical Ophthalmology Basel, in Switzerland. But it does not confirm the therapeutic effect of a mitochondrial transplant, he adds.
The mitochondria were probably not good enough. The retina has high energy consumption.
Just an update I have been on 30mg for the past few weeks. Going higher and I seem to get headaches so I’ve settled on this dose. I only weigh 60kg so I feel like I probably don’t need to get to the 40mg to get the full effects either.
The increases I saw in HRV, RHR and deep sleep might have just been noise or my bodies initial response to some healthier mitochondria. Since then all my objective markers are back to baseline from before I started. I’ll keep on the SS-31 because it subjectively helps my muscle pain but unfortunately doesn’t seem to objectively improve things (yet). I know the studies saw improvements when they did long term dosing at around 52 weeks. I’ll try to stay on this for a year or so and report back over that time.
My next experiment will be to re trial ARA-290 for my small fiber neuropathy. I also may trial KL-1333 but not sure if I’ll get into the trial if I’m honest about my peptide usage.
I’m thinking you may mean 60Kg here, unless you’ve gone on a really major weight loss program 
Yes good catch!
I have edited the post to reflect a realistic weight!