title: Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle.
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.
authors.affiliation: Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
authors.forename: Manisha
authors.initials: M
authors.lastname: Sinha
authors.forename: Young C
authors.initials: YC
authors.lastname: Jang
authors.forename: Juhyun
authors.initials: J
authors.lastname: Oh
authors.forename: Danika
authors.initials: D
authors.lastname: Khong
authors.forename: Elizabeth Y
authors.initials: EY
authors.lastname: Wu
authors.forename: Rohan
authors.initials: R
authors.lastname: Manohar
authors.forename: Christine
authors.initials: C
authors.lastname: Miller
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Regalado
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Loffredo
authors.forename: James R
authors.initials: JR
authors.lastname: Pancoast
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hirshman
authors.forename: Jessica
authors.initials: J
authors.lastname: Lebowitz
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Shadrach
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cerletti
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Kim
authors.forename: Thomas
authors.initials: T
authors.lastname: Serwold
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Goodyear
authors.forename: Bernard
authors.initials: B
authors.lastname: Rosner
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lee
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Wagers
mesh_terms: D000367:Age Factors; D000375:Aging / Q000097:blood / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D055412:Growth Differentiation Factors / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000502:physiology*; D010227:Parabiosis; D012038:Regeneration; D012060:Rejuvenation
chemical_list: D019485:Bone Morphogenetic Proteins; C119153:Gdf11 protein, mouse; D055412:Growth Differentiation Factors