The relationship between mitochondrial dynamics and age-associated diseases: from adipose tissue remodeling to cellular senescence

Mitochondrial dynamics play a central role in cellular homeostasis, and their dysregulation is increasingly implicated in aging-associated pathologies. Given the importance of mitochondrial plasticity in metabolic adaptation and stress responses, we investigated how alterations in key mitochondrial shaping proteins affect biological processes linked to aging. Using complementary in vivo and in vitro approaches, we examined the role of the mitochondrial fusion protein OPA1 in regulating adipocyte expandability, a critical determinant of metabolic health during aging. In parallel, we explored the function of the mitochondrial fission protein Fis1 in (endothelial) cell senescence, a major driver of aging-related dysfunction, through genome-wide RNAi high-content screening. Collectively, our findings aim to define how mitochondrial dynamics orchestrate cell-specific transcriptional and functional reprogramming, contributing to adipose tissue dysfunction and the onset of cellular senescence during aging.