The Non-Linear Profile of Aging: U-Shaped Expression of Myostatin, Follistatin and Intermediate Signals in a Longitudinal In Vitro Murine Cell Sarcopenia Model.

Janire Alonso-Puyo, Oihane Izagirre-Fernandez, Olatz Crende, Jesús Seco-Calvo, Ainhoa Fernandez-Atutxa, Diego Fernandez-Lazaro, Patricia Garcia-Gallastegi, Begoña Sanz

Physiology Department, Faculty of Medicine and Nursery, University of the Basque Country (UPV/EHU), Barrio Sarriena, sn., 48940 Leioa, Spain.Physiology Department, Faculty of Medicine and Nursery, University of the Basque Country (UPV/EHU), Barrio Sarriena, sn., 48940 Leioa, Spain. · pubmed

Paper

Abstract

Sarcopenia is linked to the decline in muscle mass, strength and function during aging. It affects the quality and life expectancy and can lead to dependence. The biological process underlying sarcopenia is unclear, but the proteins myostatin and follistatin are involved in the balance between muscle breakdown and synthesis. While myostatin promotes muscle breakdown, follistatin promotes muscle growth, but several works have shown an inconsistent association of these proteins with aging-related parameters in serum of older people. We aimed to know the evolution of these putative sarcopenia biomarkers along muscle aging in an in vitro model. We created and phenotyped a longitudinal murine model (C2C12 cells). Then, we analyzed the protein and genetic expression of myostatin and follistatin as well as the signaling pathway regulators mTOR and RPS6KB1. Myostatin and RPS6KB1 showed a similar tendency in both protein and genetic expression with aging (basal-up-down). Follistatin, on the other hand, shows the opposite tendency (basal-down-up). Regarding mTOR, the tendencies differ when analyzing proteins (basal-up-down) or genes (basal-down-down). Our work demonstrates a U-shape tendency for myostatin and follistatin and for the signaling pathway regulators. These results could be of the utmost importance when designing further research on seeking molecular biomarkers and/or targets for sarcopenia.

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Research summary

The paper investigates the expression profiles of myostatin and follistatin in the context of sarcopenia, which is a significant age-related condition affecting muscle mass and function. While it contributes to understanding the molecular mechanisms involved in sarcopenia, it does not directly address the root causes of aging or propose interventions that could extend lifespan or healthspan. The findings are solid but represent an incremental advance rather than a transformative breakthrough in the field of longevity research.

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