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

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.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Sciorati C,Gamberale R,Monno A,Citterio L,Lanzani C,De Lorenzo R,Ramirez GA,Esposito A,Manunta P,Manfredi AA,Rovere-Querini P

doi

10.18632/aging.202200

subject

Has Abstract

pub_date

2020-11-26 00:00:00

pages

23497-23508

issue

23

issn

1945-4589

pii

202200

journal_volume

12

pub_type

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