Damage to mitochondrial DNA (mtDNA) results in defective electron transport system (ETS) complexes, initiating a cycle of impaired oxidative phosphorylation (OXPHOS), increased reactive oxygen species (ROS) production, and chronic low-grade inflammation (inflammaging). This culminates in energy failure, cellular senescence, and progressive tissue degeneration. Rapamycin and metformin are the most extensively studied longevity drugs. Rapamycin inhibits mTORC1, promoting mitophagy, enhancing mitochondrial biogenesis, and reducing inflammation. Metformin partially inhibits Complex I, lowering reverse electron transfer (RET)-induced ROS formation and activating AMPK to stimulate autophagy and mitochondrial turnover. Both compounds mimic caloric restriction, shift metabolism toward a catabolic state, and confer preclinical—and, in the case of metformin, clinical—longevity benefits. More recently, small molecules directly targeting mitochondrial membranes and ETS components have emerged. Compounds such as Elamipretide, Sonlicromanol, SUL-138, and others modulate metabolism and mitochondrial function while exhibiting similarities to metformin and rapamycin, highlighting their potential in promoting longevity. The key question moving forward is whether these interventions should be applied chronically to sustain mitochondrial health or intermittently during episodes of stress. A pragmatic strategy may combine chronic metformin use with targeted mitochondrial therapies during acute physiological stress.
It’s pretty well established now that mitochondria function as more than organelles in one cell – they can and do move from cells to other cells. IMHO mitochondria should be thought of as a “body-wide energy management system”. There is significant therapeutic potential in “mitochondrial transplantation”, the intentional extraction, amplification, and re-introduction of mitochondria into the body.
The Economist on March 31 published this article: Mitochondria transplants could cure diseases and lengthen lives. April 27-29 I attended this conference on Long Island NY: Mitochondrial Transplantation and Next Generation Therapeutics Conference - For Physicians | Northwell Health, meeting people like Dr. James McCully from Boston Children’s Hospital, who pioneered work in ischemia/reperfusion injury recovery in a series of experiments with pigs’ hearts, and Dr. Doug Wallace from Philadelphia Children’s Hospital, who pioneered the whole field of maternal mitochondrial DNA inheritance, tracing back to “mitochondrial Eve” in Africa, and identifying disease conditions resulting from mtDNA errors.
I very much have a sense of a field that’s beginning to “take off” in terms of its impact on both therapies for multiple conditions, and more generally for aging.
One interesting aspect is how certain WBCs can act to transfer mitochondria both to and from other cells. This shows that the immune system recognises the importance of good mitochondria.
I hope SS-31 helps, I do a 40MG/day for 10 days a couple times a year in hopes that it does. Oddly with me it makes me tired and exercise is harder for the day, so I take it at night to reduce that effect. Not sure what that means, other than maybe not enough methyl factors for the improved performance?
Very interesting dose. Seems high for a single SubQ dose?
One of the highest doses I’ve seen is an IV dose of 0.25mg/kg/h over a 2 hour period. In 1 hour that would deliver - 65kg x 0.25 = 16.25mg. This would equal about 33mg over 2 hours for me at 65kg of body weight.
Not sure on the half life but in dogs its 4 hours. Spacing out doses may be the way to go.
It does seem to be well tolerated. Perhaps a 2 or 3 time per day, SubQ dose would provide a better benefit with fewer side effects? closer to what an IV would provide. I think I’ll try a morning 16mg + afternoon 16mg dosing schedule for 5 days next week.