Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle

By M. Sinha, Young C. Jang, Juhyun Oh, D. Khong, Elizabeth Y Wu, R. Manohar, Christine M. Miller, Samuel G. Regalado, F. Loffredo, James R. Pancoast and 10 more. Science, 2014

794 citations recorded by the source corpus.

Help the Aged Muscle function declines with age, as does neurogenesis in certain brain regions. Two teams analyzed the effects of heterochronic parabiosis in mice. Sinha et al. (p. 649) found that when an aged mouse shares a circulatory system with a youthful mouse, the aged mouse sees improved muscle function, and Katsimpardi et al. (p. 630) observed increased generation of olfactory neurons. In both cases, Growth Differentiation Factor 11 appeared to be one of the key components of the young blood. A circulating growth factor promotes youthful muscles and brains in aged mice. 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.

Subfields: Aging, Molecular Biology, Rheumatology

View Paper: https://www.semanticscholar.org/paper/64aed08f12a82a7fc23950498b2def1319b096fd

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

1. Brian K. Kennedy
2. V. Longo
3. T. Wyss‐Coray
4. J. Rutledge
5. H. Oh
6. P. Cohen

In Molecular Biology

1. R. Derynck
2. K. Miyazono
3. V. Longo
4. T. Wyss‐Coray
5. J. Rutledge
6. H. Oh
7. Brian K. Kennedy
8. R. Weinberg

Citations in the corpus

• TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology. (2016, background): “Recently, GDF-11 has been identified as a circulating factor in young mice, which reverses age-related dysfunction in mouse cardiac and skeletal muscle (Loffredo et al. 2013; Sinha et al. 2014).”
• A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance and healthspan (2015, background): “Postnatal growth and regeneration of the skeletal muscle requires myogenic precursors termed satellite cells (Sinha et al., 2014).”
• Measuring biological age using omics data (2022, background): “Studies on hetero-chronic parabiosis and plasma exchange in animals have demonstrated that circulating proteins can have a causal influence on ageing phenotypes across the body, including in skeletal muscle 107,108 , heart 109 and brain 15,110–112 .”