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How does the growth differentiation factor 11 regulate lifespan?

How does the growth differentiation factor 11 regulate lifespan?

Image credit: Adapted from: https://biology.stackexchange.com/questions/25890/circulating-factors-affecting-human-health-longevity

By Shubhankar Kulkarni on Aug 11, 2020

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[2] 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

[3] Loffredo FS, Steinhauser ML, Jay SM, Gannon J, Pancoast JR, Yalamanchi P, et al. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell [Internet]. 2013 May 9;153(4):828–39. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23663781

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[5] Egerman MA, Cadena SM, Gilbert JA, Meyer A, Nelson HN, Swalley SE, et al. GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration. Cell Metab [Internet]. 2015 Jul;22(1):164–74. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1550413115002223

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Creative contributions

GDF11 may promote a calorie restriction-like phenotype

In a recent study by hudobenko and colleagues, it was found that GDF11 levels were reduced as mice and humans aged. Furthermore, supplementation with GDF11 was able to decrease the risk of mortality in mice after an induced stroke. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244081/) As already mentioned, there are conflicting reports about GDF11. Egerman suggests that GDF11 levels increase in aged humans and rats. (https://pubmed.ncbi.nlm.nih.gov/26001423/) However, other researchers have suggested that the increased GDF11 level reported by Egerman was not GDF11 but was an immunoglobulin light chain that appeared due to the cross-reactivity of the specific antibody used. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748736/) Furthermore, GDF11 and GDF8 share high homology. Previous studies may not have used methods that could distinguish these two factors properly. Camparini and colleagues used LC‐MS/MS‐based assay in combination with immunoprecipitation (IP) to distinguish between the two factors, and they found that both GDF11 and GDF8 levels were reduced in aged female mice. (https://onlinelibrary.wiley.com/doi/full/10.1002/pmic.201900104). GDF11 may mimic/enhance calorie restriction-like effects to regulate lifespan. In a study, GDF11 was substantially enhanced in aged mice on calorie restriction compared to the controls. Furthermore, the usage of exogenous GDF11 was able to induce adiponectin production and improve insulin/IGF‐1 signaling. (https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13038) Therefore, GDF11 may regulate lifespan by inducing a calorie restriction-like phenotype.

by Jamila Ahmed on Aug 18, 2020

Shubhankar Kulkarni a month ago

So the primary role of GDF11 may be metabolic homeostasis and altering longevity might be a by-product....

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