Minerva Fast Track Group Fernandes

Muscle Metabolism and Ageing

One of the largest tissues in the human body is the skeletal muscle, accounting for nearly half of our body mass. It plays essential roles in movement, posture, and whole-body metabolism. Muscle health depends on a balance between anabolism (the building of cellular components) and catabolism (the breakdown and recycling of cellular material). This balance supports tissue growth, repair, and overall function. Remarkably, disruption of these processes contributes to age-related muscle loss, a common feature of ageing that can impair mobility and health.

Central to anabolic and catabolic regulation is mTORC1 (mechanistic Target Of Rapamycin Complex 1), a signaling hub that senses cues from the cellular environment and translates them into intracellular responses. In particular, active mTORC1 promotes biosynthetic activities like protein production. At the same time, it restrains catabolic processes, such as lysosome-based recycling. Importantly, mTORC1 is not only ‘on’ or ‘off’, but it can be fine-tuned to control specific tasks.

Our lab investigates how selective mTORC1 signaling is coordinated across different skeletal muscle cell types and how it changes with age. We aim to uncover how its spatial localization and functional specificity influence muscle growth, maintenance and regeneration. Our ultimate goal is to understand how to preserve muscle health over a lifetime and promote healthy ageing.

more about our research

Selected publications

Spatial and functional separation of mTORC1 signalling in response to different amino acid sources.
Fernandes, S. A., Angelidaki, D. D., Nuchel, J., Pan, J., Gollwitzer, P., Elkis, Y., Artoni, F., Wilhelm, S., Kovacevic-Sarmiento, M., & Demetriades, C.
(2024). Nat Cell Biol. doi:10.1038/s41556-024-01523-7

Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor.
Nicastro, R., Brohee, L., Alba, J., Nuchel, J., Figlia, G., Kipschull, S., Gollwitzer, P., Romero-Pozuelo, J., Fernandes, S. A., Lamprakis, A., Vanni, S., Teleman, A. A., De Virgilio, C., & Demetriades, C.
(2023).  Nat Cell Biol, 25(9), 1303-1318. doi:10.1038/s41556-023-01198-6

Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity.
Huang, W., Kew, C., Fernandes, S. A., Lohrke, A., Han, L., Demetriades, C., & Antebi, A.
(2022). Nat Aging, 2(9), 796-808. doi:10.1038/s43587-022-00275-z

The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging.
Fernandes, S. A., & Demetriades, C.
(2021).  Front Aging, 2, 707372. doi:10.3389/fragi.2021.707372

Altered in vitro muscle differentiation in X-linked myopathy with excessive autophagy.
Fernandes, S. A., Almeida, C. F., Souza, L. S., Lazar, M., Onofre-Oliveira, P., Yamamoto, G. L., Nogueira, L., Tasaki, L. Y., Cardoso, R. R., Pavanello, R. C. M., Silva, H. C. A., Ferrari, M. F. R., Bigot, A., Mouly, V., & Vainzof, M.
(2020). Dis Model Mech, 13(2). doi:10.1242/dmm.041244