Xenogeneic Mitochondrial Transplantation Improves Selected Age-Associated Phenotypes in Mice.

Abstract

Xenogeneic mitochondrial transplantation (xeno-MT) improves selected age-associated phenotypes and mitochondrial functional readouts in mice while engaging host mitochondrial quality-control-related pathways. Donor mitochondrial preparations with impaired membrane potential retained measurable activity, but both respiratory competence and in vivo efficacy declined progressively with more extensive room-temperature damage and were largely lost after complete disruption. Although beneficial effects were observed in additional donor contexts, the present study provides the most detailed in vivo evidence for yak-derived xeno-MT, and broader donor equivalence remains to be established. These findings support xeno-MT as proof-of-concept evidence of biological activity and short-term tolerability under the conditions tested, while long-term safety, germline relevance, and pathway-specific dependence remain to be defined.