The role of neurovascular health in aging
Image credit: https://www.nature.com/articles/nrneurol.2017.188?WT.feed_name=subjects_neurodegenerative-diseases
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Whether GDF11 helps in rejuvenation is debated
- GDF11 also boosted the growth of new blood vessels and neurons in the brain and skeletal muscle at the sites of injuries.
- The mouse heterochronic parabiosis model revealed that GDF11 could increase blood vessel volume as well as neurogenesis in old mice. Blood from 15-month-old mice did not decrease neural stem-cell populations in the young brain, whereas older blood (21 months) provoked a detrimental effect.
- In another parabiosis study, it was found that satellite cells sorted from aged-heterochronic mice had improved myogenic differentiation capacity as well as lower DNA damage when compared with satellite cells from aged-isochronic controls.
- In vitro exposure of aged satellite cells to GDF11 produced dose-responsive increases in satellite cell proliferation and differentiation, suggesting that GDF11 can act directly on satellite cells to alter their function. The treatment of aged mice with daily intraperitoneal injections of recombinant GDF11 for 4 weeks increased numbers of satellite cells with intact DNA.
- In a model of muscle injury, GDF11 treatment of aged mice 28 days before the injury and continued for 7 days thereafter restored more youthful profiles of myofiber caliber in regenerating muscle. Aged mice treated with GDF11 also showed increased average exercise endurance and grip strength.
- GDF11 mRNA levels rose in rat muscle with increased age.
- In vitro experiments showed that GDF11 induces the signaling pathways (SMAD 2/3 and MAPK activation) in primary and immortalized human skeletal muscle cells and that differentiation of human primary myoblasts into myotubes was inhibited by GDF11.
- Higher systemic levels of GDF11 were associated with impaired regeneration in young mice, as indicated by a greater number of very small myofibers in the GDF11-treated muscles.
- The treatment with GDF11 decreased the growth of adult and aged satellite cell cultures in a dose-dependent manner.
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Sinha M, Jang YC, Oh J, Khong D, Wu EY, Manohar R, et al. Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle. Science (80- ) [Internet]. 2014 May 9;344(6184):649–52. Available from: https://www.sciencemag.org/lookup/doi/10.1126/science.1251152
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