Growth differentiation factor 11 (GDF11) also known as bone morphogenetic protein 11 (BMP-11) is a protein that in humans is encoded by the growth differentiation factor 11 gene. GDF11 is a member of the Transforming growth factor beta family.
GDF11 acts as a cytokine and its molecular structure is identical in humans, mice and rats. The bone morphogenetic protein group is characterized by a polybasic proteolytic processing site, which is cleaved to produce a protein containing seven conserved cysteine residues.
Tissue distribution
GDF11 is expressed in many tissues, including skeletal muscle, pancreas, 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 improves neurodegenerative and neurovascular disease outcomes, increases skeletal muscle volume, and enhances muscle strength. Its wide-ranging biological effects may include the reversal of senescence in clinical applications, as well as the ability to reverse age-related pathological changes and regulate organ regeneration after injury.
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. It is also closely related to myostatin, a negative regulator of muscle growth, both structurally and phylogenetically.
Though GDF11 is 90% structurally similar to myostatin, GDF11's mechanism of action is opposite that of myostatin since it declines with age and exerts anti-aging regenerative effects in skeletal muscle in mice
Human studies
GDF11 levels fall to zero in humans at a mean age of 73.71. No endogenous GDF11 production results in the cessation of stem cell DNA repair which causes stem cells to die off and their populations fall to zero at an even faster rate. Since one cannot survive without hematopoietic, mesenchymal, etc. stems cells, this suggests that GDF11 may play a key role in maximum lifespan determination.
Elevian, 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.
It has been reported that GDF11 is down-regulated in pancreatic cancer tissue, compared with surrounding tissue, and pancreatic cell lines exhibit a low expression of the growth factor (65). This group also reported that, in a cohort of 63 PC patients, those with high GDF11 expression had significantly better survival rates in comparison with those with low GDF11 expression. These effects were related to decreased proliferation, migration and invasion, and these observations are in agreement with those reported in HCC and TNBC. GDF11 is also capable of inducing apoptosis in pancreatic cancer cell lines.