GDF11

Tissue distribution

GDF11 is expressed in many tissues, including skeletal muscle, pancreas, skin, kidney, nervous system, and retina.

Function

Gene deletion and over-expression studies indicate that GDF11 primarily regulates the embryological development of the skeletal system. It may also help regulate development of the central nervous system, blood vessels, the kidney and other tissues.

GDF11 was initially reported to improve neurodegenerative and neurovascular disease outcomes, increase skeletal muscle volume, and enhances muscle strength. However, several groups then showed that over-expression of GDF11 causes muscle wasting. In retrospect, this is not surprising, since GDF11 is 90% identical to myostatin, a known inhibitor of muscle growth. GDF11 binds the same ActRIIA/B receptors, initiating phosphorylation of the SMAD2/3 transcription factors.

Effects on cell growth and differentiation

GDF11 belongs to the transforming growth factor beta superfamily that controls anterior-posterior patterning by regulating the expression of Hox genes. It determines Hox gene expression domains and rostrocaudal identity in the caudal spinal cord.

During mouse development, GDF11 expression begins in the tail bud and caudal neural plate region. GDF knock-out mice display skeletal defects as a result of patterning problems with anterior-posterior positioning. This cytokine also inhibits the proliferation of olfactory receptor neural progenitors to regulate the number of neurons in the olfactory epithelium, and controls the competence of progenitor cells to regulate numbers of retinal ganglionic cells developing in the retina. Other studies in mice suggest that GDF11 is involved in mesodermal formation and neurogenesis during embryonic development.

GDF11 can bind type I TGF-beta superfamily receptors ACVR1B (ALK4), TGFBR1 (ALK5) and ACVR1C (ALK7), but predominantly uses ALK4 and ALK5 for signal transduction. both structurally and phylogenetically.

GDF11 is 90% structurally similar to myostatin. It was originally reported that GDF11 levels decline with age and exerts anti-aging regenerative effects in skeletal muscle in mice. However, it was later shown that the reagents used were non-selective, and the authors were measuring myostatin, not GDF11. GDF11 does not decline with age, and its downstream signaling mechanisms are similar to that of myostatin.

Human studies

Elevian, a university spin-off company whose founders include Harvard Stem Cell Institute researchers Dr. Amy Wagers, Dr. Lee Rubin, and Dr. Rich Lee, has raised $58 million in two rounds of funding to study GDF11. On June 19, 2022, the New York Times published an article about GDF11 and Elevian titled "Can a 'Magic' Protein Slow the Aging Process?". The article stated that Elevian will conduct clinical trials using GDF11 to repair stroke damage in humans starting in Q1 of 2023.

GDF11 levels in individuals with major depressive disorder are significantly lower compared to healthy controls. Administration of GDF11 in aged mice stimulates neuronal autophagy which improves memory and alleviates senescence and depression-like symptoms in a neurogenesis-independent manner. flammation, which could be the cause higher GDF11 expression in colon cancer patients..

References

References

1. (July 2005). "GDF11 forms a bone morphogenetic protein 1-activated latent complex that can modulate nerve growth factor-induced differentiation of PC12 cells". Molecular and Cellular Biology.
2. (July 2017). "The versatility and paradox of GDF 11". Pharmacology & Therapeutics.
3. "Gene GDF11". Genecards.
4. (2019). "GDF11 Implications in Cancer Biology and Metabolism. Facts and Controversies". Frontiers in Oncology.
5. (April 2019). "The role of GDF11 in aging and skeletal muscle, cardiac and bone homeostasis". Critical Reviews in Biochemistry and Molecular Biology.
6. (May 2003). "Regulation of metanephric kidney development by growth/differentiation factor 11". Developmental Biology.
7. (November 2006). "Analysis of pancreatic endocrine development in GDF11-deficient mice". Developmental Dynamics.
8. (January 2001). "Gdf11 is a negative regulator of chondrogenesis and myogenesis in the developing chick limb". Developmental Biology.
9. (April 2019). "The role of GDF11 in aging and skeletal muscle, cardiac and bone homeostasis". Critical Reviews in Biochemistry and Molecular Biology.
10. (April 2019). "The role of GDF11 in aging and skeletal muscle, cardiac and bone homeostasis". Critical Reviews in Biochemistry and Molecular Biology.
11. (August 2006). "Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis". EMBO Reports.
12. (August 2006). "The function of growth/differentiation factor 11 (Gdf11) in rostrocaudal patterning of the developing spinal cord". Development.
13. (July 1999). "Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11". Nature Genetics.
14. (January 2003). "Autoregulation of neurogenesis by GDF11". Neuron.
15. (June 2005). "GDF11 controls the timing of progenitor cell competence in developing retina". Science.
16. (November 1997). "Double muscling in cattle due to mutations in the myostatin gene". Proceedings of the National Academy of Sciences of the United States of America.
17. (October 1999). "Myostatin and the control of skeletal muscle mass". Current Opinion in Genetics & Development.
18. (2005). "Phylogenetic analysis of the myostatin gene sub-family and the differential expression of a novel member in zebrafish". Evolution & Development.
19. (May 2013). "Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy". Cell.
20. (July 2015). "GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration". Cell Metabolism.
21. (2022-07-19). "Can a 'Magic' Protein Slow the Aging Process?". The New York Times.
22. (2023-02-02). "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy". Nature Aging.
23. (2019-10-15). "GDF11 Implications in Cancer Biology and Metabolism. Facts and Controversies". Frontiers in Oncology.