Restoring Systemic GDF11 Levels Reverses Age-related Dysfunction in Mouse Skeletal Muscle

Overview

Journal Science

Specialty Science

Date 2014 May 7

PMID 24797481

Citations 422

Authors

Manisha Sinha

Young C Jang

Juhyun Oh

Danika Khong

Elizabeth Y Wu

Rohan Manohar

Christine Miller

Samuel G Regalado

Francesco S Loffredo

James R Pancoast

Michael F Hirshman

Jessica Lebowitz

Jennifer L Shadrach

Massimiliano Cerletti

Mi-Jeong Kim

Thomas Serwold

Laurie J Goodyear

Bernard Rosner

Richard T Lee

Amy J Wagers

Affiliations

Soon will be listed here.

Abstract

Parabiosis experiments indicate that impaired regeneration in aged mice is reversible by exposure to a young circulation, suggesting that young blood contains humoral "rejuvenating" factors that can restore regenerative function. Here, we demonstrate that the circulating protein growth differentiation factor 11 (GDF11) is a rejuvenating factor for skeletal muscle. Supplementation of systemic GDF11 levels, which normally decline with age, by heterochronic parabiosis or systemic delivery of recombinant protein, reversed functional impairments and restored genomic integrity in aged muscle stem cells (satellite cells). Increased GDF11 levels in aged mice also improved muscle structural and functional features and increased strength and endurance exercise capacity. These data indicate that GDF11 systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction.

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