A great deal of evidence shows that declining mitochondrial function is important to the aging process. This is directly downstream of various forms of damage, such as to mitochondrial DNA. It is also a long way downstream from a range of other forms of age-related disarray that lead to epigenetic changes that impact mitochondrial function - far enough downstream that it is unclear as to how exactly the causes of aging produce this outcome. One common view is that the quality control process of mitophagy suffers as the result of reduced production of necessary proteins, and thus damaged mitochondria accumulate.
Thus we come to mitochondrial replacement as a form of therapy. Cells do take up mitochondria from the surrounding medium, and so it is possible in principle to deliver large numbers of mitochondria into the body and expect to see results. Some progress has been made in this direction; see the biotech startup Cellvie, for example. The big unanswered question for those of us interested in rejuvenation is the degree to which the effects of this therapy will last. Will fresh mitochondria quickly succumb to the same issues of the aged environment that lead to loss of native mitochondrial function? The fastest way to find out is to try.
In recent years, advances in molecular and biochemical methodologies have led to a better understanding of mitochondrial defects and their mechanisms as the cause of various diseases, but therapies for mitochondrial disorders are still insufficient. Mitochondrial transplantation is an innovative strategy for the treatment of mitochondrial dysfunction to overcome the limitations of therapies using agents. Mitochondrial transplantation aims to transfer functional exogenous mitochondria into mitochondrion-defective cells for recovery or prevention of mitochondrial diseases. Simply put, replacing an old engine with a new one to regain its function.
Recently, a considerable number of studies demonstrated the effectiveness of mitochondrial transplantation in various diseases. There are many reports of mitotherapy in tissues, animal models and even in patients, as well as in vitro. These include neurological diseases, drug-induced liver toxicity and liver disease, including fatty liver and myocardial ischemia-reperfusion injury. Several studies have evaluated the improvement in mitochondrial function via mitochondrial transfer in neurological disease models. Researchers intravenously injected mitochondria isolated from human hepatoma cells (HepG2 cells) into neurotoxin-induced Parkinson's disease (PD) mouse brain. The recipient mouse suppressed PD progression by increasing the activity of the electron transport chain (ETC), and reduced free radical generation and apoptotic cells.
To increase mitochondrial delivery efficiency, more advanced techniques have been used. One study showed the enhanced delivery and functionality of allogenic exogenous mitochondria using peptide-mediated delivery by conjugating a cell penetrating peptide, Pep-1. The result of transplanting Pep-1-labeled mitochondria into brain tissues of a PD rat model demonstrated that mitochondrial complex I protein and mitochondrial dynamics were restored in dopaminergic neurons, which also improved oxidative DNA damage. The removal of dopaminergic neuron degeneration due to a neurotoxin was also observed in the PD rat model.