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Age Reversal Peptide discovered by Hazel Szeto, notes by John D. Furber from 2016 meetings

This is the age reversal peptide mentioned in Science as one of the top 10 discoveries of 2015.

SUMMARY: It is an experimental compound, SS-31, that reverses age decline in mitochondrial function, muscle, heart, vision. It is a 7 amino acid peptide. SS-31 improves old heart function to young levels. SS-31 reduces old heart weight to young weight. 1 dose ip inj. reverses age decline in 1 hour. Her compound, SS-31, is being developed by Stealth Biotherapeutics, a company that she co-founded. It is stable for slow release crosses the BBB. It is stable for slow release, and is suitable to inject as a depot (like birth control injected in arm). It is in 7 clinical trials.

DETAILS: Age-associated decline in enzyme activity for complex I, II, IV and decline in cytochrome c content occurs in the inner mitochondrial membrane (IMM). There is loss of cristae membranes with age in neuromuscular junctions. Cardiolipin is unique to the IMM. It has a conical structure, which when it inserts in a membrane, causes curvature of the membrane, not flat bilayer. It provides for a proton trap to keep protons close to the membrane and improve transport. Cardiolipin anchors cytochrome c to the IMM.
There is reduction in cardiolipin with age in mice. (J Biol Chem 2004, 279: Szeto) They found a compound, SS-31, that improves mitochondrial function in aged animals. (Birk Br J Pharmacol 2014) (Szeto Am J Physiol Rena Physiol 2015 308:11-21) SS peptides protect mitochondrial cristae during ischemia. They collaborate with Peter Rabinovitch (University of Washington) and Scott Powers (Univ of Flordia). They are looking at diastolic heart failure (DHF w preserved ejection fraction). Model in mouse. Echocardiography. SS-31 improves old heart function to young levels. SS-31 reduces old heart weight to young weight. How quickly can SS-31 improve muscle bioenergetics? 1 dose ip inj. reverses age decline in 1 hour (Aging Cell 2013 12:763) They collaborated with Scott Powers disuse atrophy model of soleus muscle for 1 week. But if treated with SS-31 during this week, then the muscle does not atrophy. There is an age-related decline in spatial visual function. They track the mouse's opto-kinetics. Mouse declines with age starting at 24 months. They made an eyedrop formulation of SS-31, which protects rod photoreceptor ATP-producing elements. Experimental compound SS-31 reverses age decline in mitochondrial function, muscle, heart, vision. It is a small polypeptide with 7? amino acids.
https://www.google.com/patents/US20140349942?cl=en
https://www.google.com/patents/US20100311664?cl=en

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