OPA1 orchestrates precocious senescence, degeneration of multiple organs and premature death thought inflammation and metabolic changes
Year: 2019
Type: dissertation
Abstract: A healthy mitochondrial network is essential for post-mitotic tissues like muscles. During aging sarcopenia, mitochondria-shaping machinery declines. On the contrary, lifelong exercise preserves it. OPA1 is a profusion protein that plays an essential role in mitochondrial dynamics. Interesting, OPA1 protein decreases in sedentary seniors and in 18 months-old mice. Exercise in aged mice is sufficient to increase OPA1 levels in old muscles. To address the OPA1 role in skeletal muscle and further investigate its involvement in aging, we generated muscle-specific ko mice. Indeed, Opa1 mice show severe precocious senescence, degeneration of multiple organs, and premature death. Surprisingly, mitochondrial dysfunction in muscle tissue is sufficient to directly drive metabolic changes and systemic inflammation by increasing the expression and secretion of the mitokine FGF21. Although the simultaneous deletion of OPA1 and FGF21 almost reverted the phenotype, we have new evidence that connects aging with mitochondrial dysfunction, autophagy alteration, and inflammation. Our findings underscore the central role of muscle mitochondria in the regulation of signaling pathways and the maintenance of total body metabolism, underlying the importance of a functional mitochondrial population for healthy aging.
Author: Caterina Tezze
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3159795385