Mitonuclear discordance modulates mitochondrial ageing dynamics in natural
Abstract
Mitochondrial decline is a hallmark of ageing, yet the role of intergenomic compatibility in shaping ageing trajectories remains poorly understood, particularly in an ecologically relevant framework. Hormetic interventions have been proposed as strategies to modulate metabolism and lifespan, but it is unknown how this operates in the context of mitonuclear discordance. Here, we demonstrate that mitonuclear mismatch accelerates age-related mitochondrial decline, elevates reactive oxygen species production, and shortens lifespan. Strikingly, early-life mitochondrial stress induced by dietary modulation counteracts these effects, promoting mitochondrial homeostasis and longevity. Our findings reveal mitonuclear interactions shaping ageing trajectories in natural populations and provide unique evidence that targeted interventions can act as a buffer against the detrimental impact of genetic discordance.
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Research summary
Mitonuclear mismatch accelerates mitochondrial decline and shortens lifespan, but early-life dietary stress can buffer these effects to promote longevity. This study provides ecologically relevant evidence that intergenomic compatibility influences aging trajectories and that hormetic interventions can mitigate genetic disadvantages, offering a nuanced understanding of how genetic background modulates the efficacy of longevity interventions.
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