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

Clara Sciorati, Riccardo Gamberale, Antonella Monno, Lorena Citterio, Chiara Lanzani, Rebecca De Lorenzo, Giuseppe A. Ramirez, Antonio Esposito, Paolo Manunta, Angelo A. Manfredi, Patrizia Rovere-Querini

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)23497-23508
Number of pages12
JournalAging
Volume12
Issue number23
DOIs
Publication statusPublished - Dec 2020

Keywords

  • aging
  • inflammation
  • pharmacological intervention
  • sarcopenia
  • TNF alpha

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

Fingerprint

Dive into the research topics of 'Pharmacological blockade of TNFα prevents sarcopenia and prolongs survival in aging mice'. Together they form a unique fingerprint.

Cite this