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Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle
Open accessAbstract
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.
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In the citing paper
“The first study42 focused on the monomeric forms of GDF11 and myostatin and showed that they cumulatively decrease in abundance in serum with aging42,44.”
From The central role of muscle stem cells in regenerative failure with aging (2015) · cites this paper as [42]
In the citing paper
“Importantly, there are monomeric (12.5 kDa) and dimeric (25 kDa) forms of both myostatin and GDF11, which were not distinguished using the cross-reacting antibodies in these studies42,43.”
From The central role of muscle stem cells in regenerative failure with aging (2015) · cites this paper as [42]
In the citing paper
“Accumulation of DNA damage in these stem cells can also be detected using single-cell gel electrophoresis assays38,40.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [38]
In the citing paper
“aged HSCs and muscle stem cells (also called satellite cells) show an increased number of nuclear foci that stain for the phosphorylated form of the variant histone H2A.X (γH2A.X)36–38, which serves as a marker of DNA double-strand breaks39.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [38]
In the citing paper
“A recent parabiosis study further demonstrated the potential to correct DNA damage accumulated in aging mouse satellite cells via circulating systemic factors, with associated improvement of stem cell and tissue functions38.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [38]
In the citing paper
“Intriguingly, at least part of the ‘rejuvenating’ effect of a young systemic environment appears related to the higher levels of circulating growth differentiation factor 11 (GDF11) and oxytocin present in young blood as compared to aged38,166,168,169.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [38]
In the citing paper
“Heterochronic parabiosis (a technique that links the circulatory systems of an old and young animal) can “rejuvenate” several hallmarks of aging in an old mouse (Conboy et al., 2005; Sinha et al., 2014).”
From The Aging Epigenome (2016) · cites this paper as Sinha et al., 2014
In the citing paper
“Many of the molecular signatures of aging, including stem cell exhaustion, altered intercellular signaling, and a loss of genome integrity, are reversed in an old mouse as a result of heterochronic parabiosis, suggesting that the epigenome and gene expression could also be restored to a more youthful state by this treatment (Rando and Chang, 2012; Sinha et al., 2014)”
From The Aging Epigenome (2016) · cites this paper as Sinha et al., 2014
In the citing paper
“Studies on heterochronic 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 muscle107,108, heart109 and brain15,110–112.”
From Measuring biological age using omics data (2022) · cites this paper as [108]
In the citing paper
“Old mice exhibit a decrease in circulating levels of the growth hormone GDF-11, and restoring GDF-11 levels in the old mouse was sufficient for much of the benefit for muscle function (Sinha et al., 2014).”
From Programmed cell death in aging (2015) · cites this paper as Sinha et al., 2014
In the citing paper
“Old mice exhibit a decrease in circulating levels of the growth hormone GDF-11, and restoring GDF-11 levels in the old mouse was sufficient for much of the benefit for muscle function (Sinha et al., 2014).”
From Programmed cell death in aging (2015) · cites this paper as Sinha et al., 2014
In the citing paper
“Replenishing the circulatory system with young blood has been shown to rejuvenate peripheral organs and reverse functional deficits in animals (Sinha et al, 2014).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Sinha et al, 2014
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Metadata
- Authors
- Sinha, M., Jang, Y. C., Oh, J., Khong, D., Wu, E. Y., Manohar, R., Miller, C., Regalado, S. G., Loffredo, F. S., Pancoast, J. R., Hirshman, M. F., Lebowitz, J., Shadrach, J. L., Cerletti, M., Kim, M.-J., Serwold, T., Goodyear, L. J., Rosner, B., Lee, R. T., & Wagers, A. J.
- Affiliations
- Joslin Diabetes Center (US)
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Sinha, Manisha
- Jang, Young C.
- Wagers, Amy J.
- ORCID
- Venue
- Science
- Published
- 2014-05-09
- Volume
- 344
- Issue
- 6184
- Pages
- 649-652
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4104429
- OpenAlex
- W1998004606
- Cited by
- 824
- References
- 25
- Citations by year
- 2026: 31 · 2025: 43 · 2024: 43 · 2023: 52 · 2022: 57 · 2021: 56 · 2020: 66 · 2019: 68 · 2018: 80 · 2017: 94 · 2016: 98 · 2015: 93 · 2014: 42
- FWCI
- 41.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- American Heart Association
- Abbott Laboratories
- Glenn Foundation for Medical Research
- Amgen
- Eli Lilly and Company
- Colgate-Palmolive Company
- Brigham and Women's Hospital
- Harvard University
- National Institutes of Health (1dp2od004345-01)
- Harvard Stem Cell Institute
- National Institute on Aging (R01AG033053, R01AG032977, R01AG040019)
- National Heart, Lung, and Blood Institute (U01HL100402)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK036836)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR042238)
- National Institute of Dental and Craniofacial Research (T32DE007057)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- GDF11, muscle aging, skeletal muscle regeneration, heterochronic parabiosis, satellite cells, muscle stem cells, genome stability, exercise capacity
- MeSH terms
- Age Factors, Aging, Animals, Male, Mice, Inbred C57BL, Parabiosis, Regeneration, Rejuvenation, Muscle, Skeletal, Bone Morphogenetic Proteins, Myoblasts, Skeletal, Mice, Growth Differentiation Factors
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