Fernando 2023 Commun Biol

Fernando R, Shindyapina AV, Ost M, Santesmasses D, Hu Y, Tyshkovskiy A, Yim SH, Weiss J, Gladyshev VN, Grune T, Castro JP (2023) Downregulation of mitochondrial metabolism is a driver for fast skeletal muscle loss during mouse aging. https://doi.org/10.1038/s42003-023-05595-3

» Commun Biol 6:1240. PMID: 38066057 Open Access

Fernando Raquel, Shindyapina Anastasia V, Ost Mario, Santesmasses Didac, Hu Yan, Tyshkovskiy Alexander, Yim Sun Hee, Weiss Juergen, Gladyshev Vadim N, Grune Tilman, Castro Jose Pedro (2023) Commun Biol

Abstract: Skeletal muscle aging is characterized by the loss of muscle mass, strength and function, mainly attributed to the atrophy of glycolytic fibers. Underlying mechanisms driving the skeletal muscle functional impairment are yet to be elucidated. To unbiasedly uncover its molecular mechanisms, we recurred to gene expression and metabolite profiling in a glycolytic muscle, Extensor digitorum longus (EDL), from young and aged C57BL/6JRj mice. Employing multi-omics approaches we found that the main age-related changes are connected to mitochondria, exhibiting a downregulation in mitochondrial processes. Consistent is the altered mitochondrial morphology. We further compared our mouse EDL aging signature with human data from the GTEx database, reinforcing the idea that our model may recapitulate muscle loss in humans. We are able to show that age-related mitochondrial downregulation is likely to be detrimental, as gene expression signatures from commonly used lifespan extending interventions displayed the opposite direction compared to our EDL aging signature.

• Bioblast editor: Plangger M • O2k-Network Lab: DE Leipzip Ost M

Labels: MiParea: Respiration 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS  HRR: Oxygraph-2k 

2023-12