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.