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SS-31 (Elamipretide) 

What is SS-31 ?
 

SS-31, also known as MTP-131, is a synthetic tetrapeptide specifically designed to target mitochondria. It binds with high affinity to cardiolipin, a phospholipid located within the inner mitochondrial membrane that interacts with cytochrome c. By influencing this interaction, SS-31 may help support cytochrome c in its role as an electron carrier, thereby supporting mitochondrial electron transport and ATP production, the primary source of cellular energy.

SS-31 may also help reduce the opening of the mitochondrial permeability transition pore (mPTP), a channel associated with mitochondrial dysfunction and cellular injury when excessively activated. Because abnormal mPTP opening has been implicated in neuronal cell death, this mechanism has been proposed as a potential contributor to SS-31’s effects on mitochondrial and cognitive health.

Current therapeutic uses of SS-31
 

Clinical studies on SS-31 support its use as a treatment for multiple aging-related changes, including those related to cognition, physiology, and vision.
 

Cognitive deficits

Researchers found that SS-31 administration effectively “rescued” cognitive deficits by reversing mitochondrial dysfunction in the hippocampus, the part of the brain responsible for memory and learning. This reversal, in turn, helped regulate the signaling of brain-derived neurotrophic factor, an essential protein for neuronal function.

Alzheimer’s disease

Mitochondrial dysfunction appears to be a central event in the pathogenesis of Alzheimer’s disease, so the preservation of mitochondrial health may be one of the keys to disease prevention. 
 

Stroke and traumatic brain injury

After a stroke or traumatic brain injury, oxidative stress can accumulate in the brain and lead to worse health outcomes. This is known as secondary brain injury. But here, too, SS-31 can offer protection.

Atherosclerosis

Atherosclerosis refers to a hardening of the arteries. It results, in part, from oxidative stress that activates inflammatory cells. Once activated, these cells release chemical signals that cause fats, cholesterol, and other substances to accumulate on the arterial walls. It’s a disease believed to underlie approximately 50% of all deaths in the Western Hemisphere. But with SS-31’s antioxidant action, it can potentially decrease one’s atherosclerotic risk.
 

Muscle function

Because mitochondria generate much of the energy our muscles use, it’s probably no shock that mitochondrial dysfunction contributes to muscle disorders, including age-related losses (sarcopenia). And considering SS-31’s relationship to mitochondrial health, one might expect that it could yield benefits for muscle function.

Glaucoma

Glaucoma, one of the leading causes of blindness globally, is a group of eye conditions characterized by damage to the retinal ganglion cells (RGCs). Since oxidative stress and mitochondrial dysfunction appear to contribute to RGC death, researchers have looked to SS-31 as a potential glaucoma treatment. 

Dosing and administration
 

A standard dose of SS-31 is 5mg.  You can expect to take just two doses per week, much fewer than the daily or near-daily administrations common with other peptides. When you’re ready for a dose, you ought to inject the prescribed amount into an area of subcutaneous fat, such as your stomach, a thigh, or an upper arm. You should rotate your sites to avoid irritation. Morning administration is ideal so that you can take fuller advantage of SS-31’s energizing effects.

As with other peptides, SS-31 is often cycled. That is, your schedule entails a certain period of regular administration (the “on” period) followed by a shorter period of no use at all (the “off” period). A common SS-31 cycle is three months on and one month off, totaling three cycles per year.
 

Timeline of benefits from SS-31
 

The most immediate benefit of SS-31 is an energizing effect from its action on mitochondrial function. This tends to become apparent within 1-2 weeks, as patients feel less fatigued and experience greater physical endurance.

At 2-4 weeks, SS-31’s cognitive benefits begin to take effect. At this time, you might notice an increased ability to focus and remember information.

At 8-12 weeks, and thereafter, come the antioxidant benefits. Though they aren’t as apparent as the earlier effects, you might notice a general improvement in your well-being, possibly as well as some enhancements in muscle function.



References

  1. Mayo Clinic Staff. (2024). Aging: What to expect. Mayo Clinic.

  2. Birk, A. V., et al. (2013). The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. Journal of the American Society of Nephrology, 24(8), 1250-1261.

  3. Szeto, H. H. (2014). First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology, 171(8), 2029-2050.

  4. Ramsay, R. R. (2019). Electron carriers and energy conservation in mitochondrial respiration. ChemTexts, 5(9).

  5. Wu, J., et al. (2016). BDNF pathway is involved in the protective effects of SS-31 on isoflurane-induced cognitive deficits in aging mice. Behavioural Brain Research, 305, 115-121.

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