Research Paper Advance Articles pp 23497—23508

Pharmacological blockade of TNFα prevents sarcopenia and prolongs survival in aging mice

Clara Sciorati1, , Riccardo Gamberale1, , Antonella Monno1, , Lorena Citterio2, , Chiara Lanzani2, , Rebecca De Lorenzo1,3, , Giuseppe A. Ramirez1,3, , Antonio Esposito3,4, , Paolo Manunta2,3, , Angelo A. Manfredi1,3, , Patrizia Rovere-Querini1,3, ,

  • 1 Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy
  • 2 Unit of Nephrology, IRCCS Ospedale San Raffaele, Milan, Italy
  • 3 Vita-Salute San Raffaele University, Milan, Italy
  • 4 Experimental Imaging Centre, San Raffaele Scientific Institute, Milan, Italy

Received: June 1, 2020       Accepted: October 20, 2020       Published: November 26, 2020      

https://doi.org/10.18632/aging.202200
How to Cite

Copyright: © 2020 Sciorati et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Sarcopenia is a hallmark of aging. Inflammation due to increased generation of cytokines such as TNFα, IL-1β and IL-6 has been implicated in the pathogenesis of sarcopenia. In skeletal muscle of C57BL/6 mice from 12 until 28 months of age, we observed a progressive reduction of myofiber cross sectional area, loss of type II fibers and infiltration by inflammatory cells. Muscle strength decreased in parallel. Pharmacological TNFα blockade by weekly subcutaneous injection of Etanercept from 16 to 28 months of age prevented atrophy and loss of type II fibers, with significant improvements in muscle function and mice lifespan. The effects on leukocyte recruitment were limited. These results provide a proof of principle that endogenous TNFα is sufficient to cause sarcopenia and to reduce animal survival, and open a novel perspective on novel potential pharmacological treatment strategies based on TNFα blockade to prevent the noxious events associated with aging.

Abbreviations

TNFα: Tumor necrosis factor-α; IL-6: interleukin-6; CSA: cross-sectional area; GS: gastrocnemius; IL-6: interleukin-6; G-CSF: granulocyte colony-stimulating factor; MRI: magnetic resonance imaging.