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.

Highlights

  • Aging-related sarcopenia is a process characterized by loss of skeletal muscle mass and function, with an increased risk of adverse outcomes [1, 2]

  • Tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), interleukin-10 and interleukin-15 might contribute to the loss of muscle mass [7, 8]

  • Age-related sarcopenia is associated with a reduction in the number and size of muscle fibers and causes a progressive decline in muscle function [1]

Read more

Summary

Introduction

Aging-related sarcopenia is a process characterized by loss of skeletal muscle mass and function, with an increased risk of adverse outcomes [1, 2]. TNFα is known to promote muscle wasting and cachexia [9] by promoting protein degradation while decreasing protein synthesis [10, 11] and by inhibiting muscle regeneration by blocking proliferation and differentiation of muscle stem cells [12]. In aged muscle, this inhibition seems to be preferentially mediated by TNFα released by bone marrow-derived leukocytes and TNFα genetic knockdown protects against aging-induced fiber loss and reduction of stem cell regenerative capacity [13]

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call