Rejuvenecimiento part VI

GDF11:

Growth differentiation factor 11, also known as bone morphogenetic protein 11 (BMP-11) is a protein that in humans is encoded by the GDF11 gene.[1] This BMP group of proteins is characterized by a polybasic proteolytic processing site, which is cleaved to produce a protein containing seven conserved cysteine residues.[2] GDF11 is a myostatin-homologous protein that acts as an inhibitor of nerve tissue growth. GDF11 has been shown to suppress neurogenesis through a pathway similar to that of myostatin, including stopping the progenitor cell-cycle during G-phase.[3] The similarities between GDF11 and myostatin imply a likelihood that the same regulatory mechanisms are used to control tissue size during both muscular and neural development.[3]The discovery of GDF11 was chosen as Science's scientific breakthrough of the year for 2014.[4]

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.[5] It determines Hox gene expression domains and rostrocaudal identity in the caudal spinal cord.[6]

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.[7] Peripheral supplementation of GDF11 protein (in mice) ameliorates the age-related dysfunction of skeletal muscle by rescuing the function of aged muscle stem cells.[8]

In the mouse adult central nervous system, GDF11 alone can improve the cerebral vasculature and enhance neurogenesis.[9]

This cytokine also inhibits the proliferation of olfactory receptor neuron progenitors to regulate the number of olfactory receptor neurons occurring in the olfactory epithelium,[10] and controls the competence of progenitor cells to regulate numbers of retinalganglionic cells developing in the retina.[11] Other studies in mice suggest that GDF11 is involved in mesodermal formation and neurogenesis during embryonic development. The members of this TGF-β superfamily are involved in the regulation of cell growth and differentiation not only in embryonic tissues, but adult tissues as well.[12]

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.[5]

GDF11 is closely related to myostatin, a negative regulator of muscle growth.[13][14] Both myostatin and GDF11 are involved in the regulation of cardiomyocyte proliferation. GDF11 is also a negative regulator of neurogenesis,[15][16] the production of islet progenitor cells,[17] the regulation of kidney organogenesis,[18] pancreatic development,[19] the rostro-caudal patterning in the development of spinal cords,[20] and is a negative regulator of chondrogenesis.[21]

Due to the similarities between myostatin and GDF11, the actions of GDF11 are likely regulated by WFIKKN2, a large extracellular multidomain protein consisting of follistatin, immunoglobulin, protease inhibitor, and NTR domains.[22] WFIKKN2 has a high affinity for GDF11, and previously has been found to inhibit the biological activities of myostatin.[23]

Effect on cardiac aging

GDF11 has been identified as a blood circulating factor that has the ability to reverse cardiac hypertrophy in mice as a result of hypertrophy related to aging. GDF11 gene expression and protein abundance decreases with age, and it shows differential abundance between young and old mice in parabiosis procedures, causing youthful regeneration of cardiomyocytes, a reduction in the Brain natriuretic peptide (BNP) and in the Atrial natriuretic peptide (ANP). GDF11 also causes an increase in expression of SERCA-2, an enzyme necessary for relaxation during diastolic functions.[24] GDF11 activates the TGF-β pathway in cardiomyocytes derived from pluripotent hematopoietic stem cells and suppresses the phosphorylation of Forkhead (FOX proteins) transcription factors. These effects suggest an "anti-hypertrophic effect", aiding in the reversal process of age-related hypertrophy, on the cardiomyocytes.[24]

Referencias del Factor de crecimiento Neurologico:

1. “Psiquiatría del niño y del adolescente: método, fundamentos y síndromes” María Jesus Mardomingo Sanz, 1994 [1].

2."El sistema nervioso: desde las neuronas hasta el cerebro humano” Ernesto Bustamante Zuleta [2].

3. “El factor de crecimiento nervioso” Rita Levi-Montalcini y Pietro Calissano, agosto 1979, “Libros de Investigación y Ciencia” 1990 [3].

4."Neurociencia" Dale Purves, 2007, 3 ed. [4].

5.“Participación del factor de crecimiento nervioso en la regulación de la angiogénesis ovárica” Tesis, Marcela Julio Pieper, 2006 [5] .

6.“Alzheimer: Una experiencia humana” Marcela I. Feria, 2006 [6].

Referencias del Factor de Crecimiento Epidermico(EGF):

The relationship between the epidermal growth factor (EGF) 5'UTR variant A61G and melanoma/nevus susceptibility. (PubMed id 15373781)3, 6 Randerson-Moor J.A....Bishop J.A. (2004)

EGF gene polymorphism and the risk of incident primary melanoma. (PubMed id 15087376)3, 6 Amend K.L....Gruber S.B. (2004)

Association of EGF polymorphism with schizophrenia in Finnish men. (PubMed id 15129177)3, 6 Anttila S....Leinonen E. (2004)

EGF +61 gene polymorphism and susceptibility to and prognostic markers in cutaneous malignant melanoma. (PubMed id 14520709)3, 6 McCarron S.L....Howell W.M. (2003)

Association between functional polymorphism in EGF gene and malignant melanoma. (PubMed id 11844511)3, 6 Shahbazi M....Hutchinson I.V. (2002)

The primary structure of human EGF produced by genetic engineering, studied by high-performance tandem mass spectrometry. (PubMed id 2789514)3, 4 Furuya M.... Hirayama K. (1989)

FGF2 transcript levels are positively correlated with EGF and IGF-1 in the malignant endometrium. (PubMed id 18006148)1, 3 Soufla G....Spandidos D.A. (2008)

EGF promoter SNPs, plasma EGF levels and risk of breast cancer in Chinese women. (PubMed id 17940864)1, 3 Wang Y....Shen H. (2008)

A functional epidermal growth factor (EGF) polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome. (PubMed id 18483390)1, 3 Lanuti M....Christiani D.C. (2008)

Differential activation of epidermal growth factor (EGF) receptor downstream signaling pathways by betacellulin and EGF. (PubMed id 15192046)1, 3 Saito T....Mori M. (2004)

Clinical significance of EGF and EGFR expression changes in cryptorchid boys. (PubMed id 12508124)1, 3 Yang G.S....Chen Z.D. (2002)

Expression of insulin-like growth factor binding protein-3 (IGFBP-3) in human keratinocytes is regulated by EGF and TGFbeta1. (PubMed id 10199559)1, 3 Edmondson S.R....Werther G.A. (1999)

Expression of intermediate filaments, EGF and TGF-alpha in early human kidney development. (PubMed id 18080773)1, 3 Carev D....Saraga-Babic M. (2008)

Expression analysis of peptide growth factors VEGF, FGF2, TGFB1, EGF and IGF1 in prostate cancer and benign prostatic hyperplasia. (PubMed id 16820871)1, 3 Soulitzis N....Spandidos D.A. (2006)

Expression of epidermal growth factor (EGF) receptor and its ligands, EGF and transforming growth factor-alpha, in human fallopian tubes. (PubMed id 1639032)1, 3 Lei Z.M. and Rao C.V. (1992)

Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR. (PubMed id 17617058)1, 3 Geraghty K.M....MacKintosh C. (2007)

SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation. (PubMed id 15485655)1, 3 Huang L.... Tsuchida N. (2004)

EGF signalling amplification induced by dynamic clustering of EGFR. (PubMed id 15485674)1, 3 Ichinose J....Sako Y. (2004)

Referencias del Factor de Crecimiento Derivado de las Plaquetas(PDGF):

1. -Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes». Science 243 (4892): pp. 800–4. 1989. doi:10.1126/science.2536956. PMID 2536956.
2. - Heidaran MA, Pierce JH, Yu JC, et al. (25 de octubre de 1991). «Role of alpha beta receptor heterodimer formation in beta platelet-derived growth factor (PDGF) receptor activation by PDGF-AB». J. Biol. Chem. 266 (30): pp. 20232–7. PMID 1657917. http://www.jbc.org/cgi/content/abstract/266/30/20232.
3. - Heidaran MA, Pierce JH, Jensen RA, Matsui T, Aaronson SA (5 de noviembre de 1990). «Chimeric alpha- and beta-platelet-derived growth factor (PDGF) receptors define three immunoglobulin-like domains of the alpha-PDGF receptor that determine PDGF-AA binding specificity». J. Biol. Chem. 265 (31): pp. 18741–4. PMID 2172231. http://www.jbc.org/cgi/content/abstract/265/31/18741.
4. - Yu JC, Li W, Wang LM, Uren A, Pierce JH, Heidaran MA (1995). «Differential requirement of a motif within the carboxyl-terminal domain of alpha-platelet-derived growth factor (alpha PDGF) receptor for PDGF focus forming activity chemotaxis, or growth». J. Biol. Chem. 270 (13): pp. 7033–6. doi:10.1074/jbc.270.13.7033. PMID 7706238. http://www.jbc.org/cgi/content/full/270/13/7033.
5. -PDGF Pathways». Consultado el 17-11-2007.
6. - Barres BA, Hart IK, Coles HSR, Burne JF, Voyvodic JT, Richardson WD, Raff MC (1992). «Cell Death and Control of Cell Survival in the Oligodendrocyte Lineage». Cell 70 (1): pp. 31–46. doi:10.1016/0092-8674(92)90531-G. PMID 1623522.
7. - a b MeSH Proto-Oncogene+Proteins+c-sis
8. -Paul D, Lipton A, Klinger I (1971). «Serum factor requirements of normal and simian virus 40-transformed 3T3 mouse fibroplasts.». Proc Natl Acad Sci U S A. 68 (3): pp. 645–52. PMID 5276775.
9. - McClintock J, Chan I, Thaker S, Katial A, Taub F, Aotaki-Keen A, Hjelmeland L (1992). «Detection of c-sis proto-oncogene transcripts by direct enzyme-labeled cDNA probes and in situ hybridization». In Vitro Cell Dev Biol 28A (2): pp. 102–8. doi:10.1007/BF02631013. PMID 1537750

Referencias del Factor de crecimiento transformante beta(TGF-ß):

- Kumar, MBBS, MD, FRCPath, V.; Abul K. Abbas, MBBS, Nelson Fausto, MD and Jon Aster, MD. «Ch3-Tissue Renewal, Regeneration and Repair». En Saunders (Elsevier). Robbins & Cotran Pathologic Basis of Disease (8th edición).

Referencias del Factor de Crecimiento Fibroblastico (FGF):

-Kumar, MBBS, MD, FRCPath, V.; Abul K. Abbas, MBBS, Nelson Fausto, MD and Jon Aster, MD. «Ch3-Tissue Renewal,

-Regeneration and Repair». En Saunders (Elsevier). Robbins & Cotran Pathologic Basis of Disease (8th edición).

Referencias del factor de crecimiento del endotelio vascular(VEGF):

1. -Saunders (Elsevier), ed. «Ch3-Tissue Renewal, Regeneration and Repair». Robbins and Cotran Pathologic Basis of Disease (8th edición).
2. -Holmes K, Roberts OL, Thomas AM, Cross MJ. (Oct 2007). «Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition.». Cell Signal. 19 (10): pp. 2003–2012. PMID 17658244.
3. -Amo Y, Masuzawa M, Hamada Y, Katsuoka K (January 2004). «Serum concentrations of vascular endothelial growth factor-D in angiosarcoma patients». Br. J. Dermatol. 150 (1): pp. 160–1. doi:10.1111/j.1365-2133.2004.05751.x. PMID 14746640.
4. -Liu E, Morimoto M, Kitajima S, et al. (July 2007). «Increased expression of vascular endothelial growth factor in kidney leads to progressive impairment of glomerular functions». J. Am. Soc. Nephrol. 18 (7): pp. 2094–104. doi:10.1681/ASN.2006010075. PMID 17554151.
5. -Bergers G, Hanahan D (August 2008). «Modes of resistance to anti-angiogenic therapy». Nat. Rev. Cancer 8 (8): pp. 592–603. doi:10.1038/nrc2442. PMID 18650835.

Referencias del Factor de Crecimiento Insulinico Tipo I(IGF-1):

1. - “Descubren el mecanismo responsable de la pérdida de memoria propia de la vejez” en novaciencia.com.
2. - Jl. Trejo, J. Piriz, M. V. Llorens-Martin, A. M. Fernández, M. Bolós, D. LeRoith, A. Núñez e I. Torres-Aleman; “Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects”

Referencias del Factor de crecimiento del Hepatocito(HGF):

1. - Kumar, MBBS, MD, FRCPath, V.; Abul K. Abbas, MBBS, Nelson Fausto, MD and Jon Aster, MD. «Ch3-Tissue Renewal, Regeneration and Repair». En Saunders (Elsevier). Robbins & Cotran Pathologic Basis of Disease (8th edición).

Referencias del Factor de crecimiento (GDF11) growth differentiation factor 11 :

1.Ge G, Hopkins DR, Ho WB, Greenspan DS (July 2005). "GDF11 forms a bone morphogenetic protein 1-activated latent complex that can modulate nerve growth factor-induced differentiation of PC12 cells". Mol. Cell. Biol. 25 (14): 5846–58.doi:10.1128/MCB.25.14.5846-5858.2005. PMC 1168807. PMID 15988002.

2."Gene GDF11". Genecards. Retrieved 25 May 2013.

3. "Recombinant-Human GDF11".

4. http://www.thecherrycreeknews.com/young-blood-reverses-aging-breakthrough-2014-gdf11/

5.Andersson O, Reissmann E, Ibáñez C (2006). "Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis". EMBO Rep 7 (8): 831–7.doi:10.1038/sj.embor.7400752. PMC 1525155. PMID 16845371.

6.Liu J (2006). "The function of growth/differentiation factor 11 (Gdf11) in rostrocaudal patterning of the developing spinal cord". Development 133 (15): 2865–74. doi:10.1242/dev.02478. PMID 16790475.

7. McPherron, AC; Lawler, AM; Lee, SJ (July 1999). "Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11.". Nature Genetics 22 (3): 260–4. doi:10.1038/10320. PMID 10391213.

8. Sinha, M; Jang, YC; Oh, J; Khong, D; ... Wagers, AJ (May 2014). "Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle.". Science 344 (6184): 649-52. doi:10.1126/science.1251152. PMID 24797481.

9.Katsimpardi, L; Litterman, NK; Schein PA; Miller CM; Loffredo FS; Wojtkiewicz GR (May 2014). "Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors.". Science 344 (6184): 630–4.doi:10.1126/science.1251141. PMID 24797482.

10.Wu H, Ivkovic S, Murray R, Jaramillo S, Lyons K, Johnson J, Calof A (2003). "Autoregulation of neurogenesis by GDF11". Neuron 37 (2): 197–207. doi:10.1016/S0896-6273(02)01172-8. PMID 12546816.

11.Kim J, Wu H, Lander A, Lyons K, Matzuk M, Calof A (2005). "GDF11 controls the timing of progenitor cell competence in developing retina". Science 308 (5730):1927-30. doi:10.1126/science.1110175. PMID 15976303.

12."GDF11". Genecards.

13.McPherron, Alexandra; Se-Jin Lee (November 1997). "Double muscling in cattle due to mutations in the myostatin gene". PNAS 94 (23): 12457-12461. doi:10.1073/pnas.94.23.12457. PMC 24998. PMID 9356471. Retrieved 25 May 2013.

14.Lee, SJ; McPherron, AC (October 1999). "Myostatin and the control of skeletal muscle mass.". Current opinion in genetics & development 9 (5): 604–7. doi:10.1016/S0959-437X(99)00004-0. PMID 10508689.

15.Wu, HH; Ivkovic, S; Murray, RC; Jaramillo, S; Lyons, KM; Johnson, JE; Calof, AL (Jan 23, 2003). "Autoregulation of neurogenesis by GDF11.". Neuron 37 (2): 197–207. doi:10.1016/S0896-6273(02)01172-8. PMID 12546816.

16.Ge, G; Hopkins, DR; Ho, WB; Greenspan, DS (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 25(14): 5846–58. doi:10.1128/MCB.25.14.5846-5858.2005. PMC 1168807. PMID 15988002.

17.Harmon, EB; Apelqvist, AA; Smart, NG; Gu, X; Osborne, DH; Kim, SK (December 2004). "GDF11 modulates NGN3+ islet progenitor cell number and promotes beta-cell differentiation in pancreas development.". Development (Cambridge, England) 131 (24): 6163–74. doi:10.1242/dev.01535. PMID 15548585.

18.Esquela, AF; Lee, SJ (May 15, 2003). "Regulation of metanephric kidney development by growth/differentiation factor 11.". Developmental biology 257 (2): 356–70. doi:10.1016/s0012-1606(03)00100-3. PMID 12729564.

19.Dichmann, DS; Yassin, H; Serup, P (November 2006). "Analysis of pancreatic endocrine development in GDF11-deficient mice.". Developmental dynamics : an official publication of the American Association of Anatomists 235 (11): 3016–25.doi:10.1002/dvdy.20953. PMID 16964608.

20.Liu, JP (August 2006). "The function of growth/differentiation factor 11 (Gdf11) in rostrocaudal patterning of the developing spinal cord.". Development (Cambridge, England) 133 (15): 2865–74. doi:10.1242/dev.02478. PMID 16790475.

21.Gamer, LW; Cox, KA; Small, C; Rosen, V (Jan 15, 2001). "Gdf11 is a negative regulator of chondrogenesis and myogenesis in the developing chick limb.". Developmental biology 229 (2): 407-20. doi:10.1006/dbio.2000.9981. PMID 11203700.

22."Both WFIKKN1 and WFIKKN2 Have High Affinity for Growth and Differentiation Factors 8 and 11". NCBI. Retrieved 25 May 2013.

23."WJIKKN2". Geneards. Retrieved 25 May 2013.

24.Loffredo, Francesco; et al (9 May 2013). "Growth Differentiation Factor Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy". Cell 153: 828–839. doi:10.1016/j.cell.2013.04.015.

Further reading:

• Kondás K, Szláma G, Trexler M, Patthy L (2008). "Both WFIKKN1 and WFIKKN2 have high affinity for growth and differentiation factors 8 and 11.". J. Biol. Chem. 283 (35): 23677–84. doi:10.1074/jbc.M803025200. PMC 3259755.PMID 18596030.
• Lee SJ, McPherron AC (1999). "Myostatin and the control of skeletal muscle mass.". Curr. Opin. Genet. Dev. 9 (5): 604–7. doi:10.1016/S0959-437X(99)00004-0. PMID 10508689.
• Hocking JC, Hehr CL, Chang RY, et al. (2008). "TGFbeta ligands promote the initiation of retinal ganglion cell dendrites in vitro and in vivo.". Mol. Cell. Neurosci. 37 (2): 247–60. doi:10.1016/j.mcn.2007.09.011. PMID 17997109.
• Hannan NR, Jamshidi P, Pera MF, Wolvetang EJ (2009). "BMP-11 and myostatin support undifferentiated growth of human embryonic stem cells in feeder-free cultures.". Cloning Stem Cells 11 (3): 427–35. doi:10.1089/clo.2009.0024.PMID 19751112.
• Gamer LW, Wolfman NM, Celeste AJ, et al. (1999). "A novel BMP expressed in developing mouse limb, spinal cord, and tail bud is a potent mesoderm inducer in Xenopus embryos.". Dev. Biol. 208 (1): 222–32.doi:10.1006/dbio.1998.9191. PMID 10075854.
• Yokoe T, Ohmachi T, Inoue H, et al. (2007). "Clinical significance of growth differentiation factor 11 in colorectal cancer.". Int. J. Oncol. 31 (5): 1097–101. doi:10.3892/ijo.31.5.1097. PMID 17912435.
• Schneyer AL, Sidis Y, Gulati A, et al. (2008). "Differential antagonism of activin, myostatin and growth and differentiation factor 11 by wild-type and mutant follistatin.". Endocrinology 149 (9): 4589–95. doi:10.1210/en.2008-0259.PMC 2553374. PMID 18535106.
• McPherron AC, Lawler AM, Lee SJ (1999). "Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11.". Nat. Genet. 22 (3): 260–4. doi:10.1038/10320. PMID 10391213.
• Szumska D, Pieles G, Essalmani R, et al. (2008). "VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5.". Genes Dev. 22 (11): 1465–77. doi:10.1101/gad.479408.PMC 2418583. PMID 18519639.
• Hillier LD, Lennon G, Becker M, et al. (1996). "Generation and analysis of 280,000 human expressed sequence tags.".Genome Res. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549.

Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors

1. Lida Katsimpardi1,2,*,

2. Nadia K. Litterman1,2,

3. Pamela A. Schein1,2,

4. Christine M. Miller1,2,3,

5. Francesco S. Loffredo1,2,4,

6. Gregory R. Wojtkiewicz5,

7. John W. Chen5,

8. Richard T. Lee1,2,4,

9. Amy J. Wagers1,2,3,

10. Lee L. Rubin1,2,*

author.mail: lee_rubin@harvard.edu (L.L.R.); lida_katsimpardi@harvard.edu (L.K.)

EDITOR'S SUMMARY

In the adult central nervous system, the vasculature of the neurogenic niche regulates neural stem cell behavior by providing circulating and secreted factors. Age-related decline of neurogenesis and cognitive function is associated with reduced blood flow and decreased numbers of neural stem cells. Therefore, restoring the functionality of the niche should counteract some of the negative effects of aging. We show that factors found in young blood induce vascular remodeling, culminating in increased neurogenesis and improved olfactory discrimination in aging mice. Further, we show that GDF11 alone can improve the cerebral vasculature and enhance neurogenesis. The identification of factors that slow the age-dependent deterioration of the neurogenic niche in mice may constitute the basis for new methods of treating age-related neurodegenerative and neurovascular diseases.

GDF11 in Homo sapiens Systemic factors mediate reversible age-associated brain dysfunction.Mendelsohn AR, Larrick JW.Rejuvenation Res. 2014 Dec;17(6):525-8. doi: 10.1089/rej.2014.1643.

GDF11 forms a bone morphogenetic protein 1-activated latent complex that can modulate nerve growth factor-induced differentiation of PC12 cells.

(PMID:15988002 PMCID:PMC1168807)

Growth differentiation Factor 11 is an encephalic regionalizing factor in neural differentiated mouse embryonic stem cells.Vanbekbergen N, Hendrickx M, Leyns L.

BMC Res Notes. 2014 Oct 29;7:766. doi: 10.1186/1756-0500-7-766.

Effective RNA-silencing strategy of Lv-MSTN/GDF11 gene and its effects on the growth in shrimp, Litopenaeus vannamei.

Lee JH, Momani J, Kim YM, Kang CK, Choi JH, Baek HJ, Kim HW.

Comp Biochem Physiol B Biochem Mol Biol. 2015 Jan;179:9-16. doi: 10.1016/j.cbpb.2014.09.005. Epub 2014 Sep 20.

Young blood.

Hall SS.Science. 2014 Sep 12;345(6202):1234-7. doi: 10.1126/science.345.6202.1234.

Identification of TGF-β, inhibin βA and follistatin paralogs in the rainbow trout genome.

de Mello F, Streit DP Jr, Sabin N, Gabillard JC.

Comp Biochem Physiol B Biochem Mol Biol. 2014 Nov-Dec;177-178:46-55. doi: 10.1016/j.cbpb.2014.07.006. Epub 2014 Aug 20.

An ingredient for the elixir of youth.Andersen RE, Lim DA.

Cell Res. 2014 Dec;24(12):1381-2. doi: 10.1038/cr.2014.107. Epub 2014 Aug 12.

Young blood.

Laviano A.

N Engl J Med. 2014 Aug 7;371(6):573-5. doi: 10.1056/NEJMcibr1407158.

Rejuvenation: it's in our blood.

Bitto A, Kaeberlein M.

Cell Metab. 2014 Jul 1;20(1):2-4. doi: 10.1016/j.cmet.2014.06.007.

GDF11/myostatin and aging.

Patel VK, Demontis F.

Aging (Albany NY). 2014 May;6(5):351-2.

Intertissue control of the nucleolus via a myokine-dependent longevity pathway.

Demontis F, Patel VK, Swindell WR, Perrimon N.

Cell Rep. 2014 Jun 12;7(5):1481-94. doi: 10.1016/j.celrep.2014.05.001. Epub 2014 May 29.

Aging. 'Rejuvenation factor' in blood turns back the clock in old mice.

Kaiser J.

Science. 2014 May 9;344(6184):570-1. doi: 10.1126/science.344.6184.570. No abstract available.

Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors.

Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS, Wojtkiewicz GR, Chen JW, Lee RT, Wagers AJ, Rubin LL.

Science. 2014 May 9;344(6184):630-4. doi: 10.1126/science.1251141. Epub 2014 May 5.

Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle.

Sinha M, Jang YC, Oh J, Khong D, Wu EY, Manohar R, Miller C, Regalado SG, Loffredo FS, Pancoast JR, Hirshman MF, Lebowitz J, Shadrach JL, Cerletti M, Kim MJ, Serwold T, Goodyear LJ, Rosner B, Lee RT, Wagers AJ.

Science. 2014 May 9;344(6184):649-52. doi: 10.1126/science.1251152. Epub 2014 May 5.

Identification and expression of a novel transcript of the growth and differentiation factor-11 gene.

Jeanplong F, Falconer SJ, Oldham JM, Maqbool NJ, Thomas M, Hennebry A, McMahon CD.

Mol Cell Biochem. 2014 May;390(1-2):9-18. doi: 10.1007/s11010-013-1949-3. Epub 2013 Dec 31.

An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy.

Lach-Trifilieff E, Minetti GC, Sheppard K, Ibebunjo C, Feige JN, Hartmann S, Brachat S, Rivet H, Koelbing C, Morvan F, Hatakeyama S, Glass DJ.

Mol Cell Biol. 2014 Feb;34(4):606-18. doi: 10.1128/MCB.01307-13. Epub 2013 Dec 2.

Transcriptional basis for the inhibition of neural stem cell proliferation and migration by the TGFβ-family member GDF11.

Williams G, Zentar MP, Gajendra S, Sonego M, Doherty P, Lalli G.PLoS One. 2013 Nov 7;8(11):e78478. doi: 10.1371/journal.pone.0078478. eCollection 2013

-GDF11 forms a bone morphogenetic protein 1-activated latent complex that can modulate nerve growth factor-induced differentiation of PC12 cells. (PubMed id 15988002)1, 3, 9 Ge G....Greenspan D.S. (Mol. Cell. Biol. 2005)

-A large-scale candidate gene association study of age at menarche and age at natural menopause. (PubMed id 20734064)1, 4 He C....Hunter D.J. (Hum. Genet. 2010)

-A novel BMP expressed in developing mouse limb, spinal cord, and tail bud is a potent mesoderm inducer in Xenopus embryos. (PubMed id 10075854)1, 2 Gamer L.W....Rosen V. (Dev. Biol. 1999)

-Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11. (PubMed id 10391213)1, 2 McPherron A.C.... Lee S.-J. (Nat. Genet. 1999)

-Clinical significance of growth differentiation factor 11 in colorectal cancer. (PubMed id 17912435)1, 9 Yokoe T....Mori M. (Int. J. Oncol. 2007)

-BMP-11 and myostatin support undifferentiated growth of human embryonic stem cells in feeder-free cultures. (PubMed id 19751112)1 Hannan N.R....Wolvetang E.J. (Cloning Stem Cells 2009)

-TGFbeta ligands promote the initiation of retinal ganglion cell dendrites in vitro and in vivo. (PubMed id 17997109)1 Hocking J.C....McFarlane S. (Mol. Cell. Neurosci. 2008)

-VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5. (PubMed id 18519639)1 Szumska D....Bhattacharya S. (amp 2008)

-Both WFIKKN1 and WFIKKN2 have high affinity for growth and differentiation factors 8 and 11. (PubMed id 18596030)1 KondA!s K....Patthy L. (J. Biol. Chem. 2008)

-Differential antagonism of activin, myostatin and growth and differentiation factor 11 by wild-type and mutant follistatin. (PubMed id 18535106)1 Schneyer A.L....Krasney P.A. (Endocrinology 2008)