Mitochondria in the Crossfire: How Early-Life Interventions Shape Lifelong Health
Author(s): Aida Adlimoghaddam
This review examines early-life interventions in mice and their lasting impact on development, mitochondrial function, lifespan, healthspan, and aging, with potential implications for human health. Mitochondria, as central regulators of cellular energy, metabolism, and stress responses, are increasingly recognized as critical mediators of how early-life experiences shape long-term physiological outcomes. We first review studies employing diverse early-life interventions, including dietary modifications, hormonal treatments, and pharmacological interventions, and also explore their effects on aging, longevity, and mitochondrial integrity. These interventions can modify mitochondrial activity, bioenergetics, morphology, and oxidative stress resilience, thereby influencing organismal health across the lifespan. The review further highlights critical factors that modulate the efficacy of early-life interventions, such as timing, duration, sex, genetic background, and environmental context, all of which can dictate mitochondrial responses and downstream physiological consequences. By integrating insights from mitochondrial biology, developmental programming, and aging research, this review underscores the promise of early-life interventions not only for enhancing lifespan and healthspan in model organisms but also for informing interventions that may mitigate the long-term consequences of early-life adversity in humans.