Mitochondria-targeted therapy in anti-aging medicine: A review

Background: Mitochondrial dysfunction associated with aging is a major contributor to cellular senescence and systemic decline in metabolism. The core concept behind mitochondria-targeted anti-aging therapy is to restore cellular health by replacing damaged mitochondria with healthy, fully functional ones. However, directly transplanting isolated mitochondria is challenging as they degrade rapidly outside the protective environment of a cell. Large extracellular vesicles (microvesicles [MVs]) may provide a protected, cell-like microenvironment that helps preserve mitochondrial integrity during extracellular transport. According to published data, such MVs can facilitate intercellular transfer of mitochondria and biomolecules involved in regulating mitochondrial functional activity. Following internalization, the transferred mitochondria integrate into the metabolic pathways of the recipient cell. They produce adenosine triphosphate, help rebalance mitochondrial dynamics, stimulate the removal of defective mitochondria from the cell (mitophagy), and generate new, functionally competent mitochondria (mitogenesis). Objective: The review evaluates the potential of MV-mediated mitochondrial transfer as a viable and immunologically adaptable strategy for restoring mitochondrial function and inhibiting cellular aging. Mitochondria containing MVs (M-MVs), isolated from cells of young donors or tumor cell lines, can serve as transport vehicles for the intercellular transfer of mitochondria. The functional activity of transferred mitochondria can be prolonged through both non-pharmacological (intermittent hypoxia, physical exercise, caloric restriction, antioxidant nutrition) and pharmacological interventions (rapamycin, metformin, resveratrol, and others), which support mitophagy and mitogenesis. Conclusion: MV mediated mitochondrial transfer can establish a physiologically grounded platform for conducting complex therapy aimed at preventing and treating diseases associated with cellular aging.