Granet, J. | bioRxiv Science

bioRxiv2024

Impact of physical activity on physical performance, mitochondrial bioenergetics, ROS production and calcium handling across the human adult lifespan

Aging-related muscle atrophy and weakness contribute to loss of mobility, falls and disability. Mitochondrial dysfunction is widely considered a key contributing mechanism to muscle aging. However, mounting evidence position physical activity as a confounding factor, making unclear whether muscle mitochondria accumulate bona fide defects with aging. To disentangle aging from physical activity-related mitochondrial adaptations, we functionally profiled skeletal muscle mitochondria in 51 inactive and 88 active men aged 20-93. Physical activity status conferred partial protection against age-related decline in physical performance. A trend for reduced muscle mitochondrial respiration with aging was observed in inactive but not in active participants, indicating that aging per se does not alter mitochondrial respiratory capacity. Mitochondrial reactive oxygen species (ROS) production was unaffected by aging and active participants displayed higher ROS production. In contrast, mitochondrial calcium retention capacity decreased with aging regardless of physical activity status and correlated with muscle mass, performance and the stress-responsive metabokine GDF15. Targeting mitochondrial calcium handling may hold promise for treating aging-related muscle impairments.

cell biology↗

bioRxiv2023

Deciphering circulating tumor cells binding in a microfluidic system thanks to a parameterized mathematical model

The spread of metastases is a crucial process in which some questions remain unanswered. In this work, we focus on tumor cells circulating in the bloodstream, the so-called Circulating Tumor Cells (CTCs). Our aim is to characterize their trajectories under the influence of hemodynamic and adhesion forces. We focus on already available in vitro measurements performed with a microfluidic device corresponding to the trajectories of CTCs - without or with different protein depletions - interacting with an endothelial layer. A key difficulty is the weak knowledge of the fluid velocity that has to be reconstructed. Our strategy combines a differential equation model - a Poiseuille model for the fluid velocity and an ODE system for the cell adhesion model - and a robust and well-designed calibration procedure. The parameterized model quantifies the strong influence of fluid velocity on adhesion and confirms the expected role of several proteins in the deceleration of CTCs. Finally, it enables the generation of synthetic cells, even for unobserved experimental conditions, opening the way to a digital twin for flowing cells with adhesion.

cancer biology↗