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Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy
Open accessAbstract
The most common form of heart failure occurs with normal systolic function and often involves cardiac hypertrophy in the elderly. To clarify the biological mechanisms that drive cardiac hypertrophy in aging, we tested the influence of circulating factors using heterochronic parabiosis, a surgical technique in which joining of animals of different ages leads to a shared circulation. After 4 weeks of exposure to the circulation of young mice, cardiac hypertrophy in old mice dramatically regressed, accompanied by reduced cardiomyocyte size and molecular remodeling. Reversal of age-related hypertrophy was not attributable to hemodynamic or behavioral effects of parabiosis, implicating a blood-borne factor. Using modified aptamer-based proteomics, we identified the TGF-β superfamily member GDF11 as a circulating factor in young mice that declines with age. Treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging.
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“the rejuvenation strategies based on the use of blood-borne systemic factors identified in parabiosis experiments (Conboy et al., 2005; Loffredo et al., 2013; Villeda et al., 2011).”
From The Hallmarks of Aging (2013) · cites this paper as Loffredo et al., 2013
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“Excitingly, proof of principle exists for rejuvenation through blood-borne systemic factors (Conboy et al., 2005; Loffredo et al., 2013; Villeda et al., 2011).”
From The Hallmarks of Aging (2013) · cites this paper as Loffredo et al., 2013
In the citing paper
“The first study42 focused on the monomeric forms of GDF11 and myostatin and showed that they cumulatively decrease in abundance in serum with aging42,44.”
From The central role of muscle stem cells in regenerative failure with aging (2015) · cites this paper as [44]
In the citing paper
“Intriguingly, at least part of the ‘rejuvenating’ effect of a young systemic environment appears related to the higher levels of circulating growth differentiation factor 11 (GDF11) and oxytocin present in young blood as compared to aged38,166,168,169.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [168]
In the citing paper
“Studies on heterochronic parabiosis and plasma exchange in animals have demonstrated that circulating proteins can have a causal influence on ageing phenotypes across the body, including in skeletal muscle107,108, heart109 and brain15,110–112.”
From Measuring biological age using omics data (2022) · cites this paper as [109]
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2013 ACCF/AHA Guideline for the Management of Heart Failure
Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D. E., Drazner, M. H., Fonarow, G. C., Geraci, S. A., Horwich, T., Januzzi, J. L., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.05.019 · Cited by 12,536
Tuerk, C., & Gold, L. (1990) · Science · doi:10.1126/science.2200121 · Cited by 10,421 · cited 1×
“SOMAmers (Slow Off-rate Modified Aptamers) are nucleic acid-based protein binding reagents evolved through SELEX (Tuerk and Gold, 1990) to bind protein targets.”
Levy, D., Garrison, R. J., Savage, D. D., Kannel, W. B., & Castelli, W. P. (1990) · New England Journal of Medicine · doi:10.1056/nejm199005313222203 · Cited by 5,699
Hunt, S. A., Abraham, W. T., Chin, M. H., Feldman, A. M., Francis, G. S., Ganiats, T. G., Jessup, M. L., Konstam, M. A., MANCINI, D. M., Michl, K., et al. (2009) · Circulation · doi:10.1161/circulationaha.109.192065 · Cited by 3,739
Sandri, M., Sandri, C., Gilbert, A., Skurk, C., Calabria, E., Picard, A., Walsh, K., Schiaffino, S., Lecker, S. H., & Goldberg, A. L. (2004) · Cell · doi:10.1016/s0092-8674(04)00400-3 · Cited by 3,012 · cited 1×
“Although it is plausible that the antihypertrophic effect of rGDF11 is mediated by FoxO-dependent proteasomemediated protein degradation (Sandri et al., 2004), our data do not explain the differential effects of rGDF11 and myostatin.”
Rejuvenation of aged progenitor cells by exposure to a young systemic environment
Conboy, I. M., Conboy, M. J., Wagers, A. J., Girma, E. R., Weissman, I. L., & Rando, T. A. (2005) · Nature · doi:10.1038/nature03260 · Cited by 2,287 · cited 4×
“…can significantly impact the function of aging tissues, as indicated by the restoration of appropriate activation and function of endogenous, ''old'' skeletal muscle satellite cells and successful muscle repair after injury following exposure to a ''youthful'' systemic milieu (Conboy et al., 2005).”
InfluentialSelf-citationThe ageing systemic milieu negatively regulates neurogenesis and cognitive function
Villeda, S. A., Luo, J., Mosher, K. I., Zou, B., Britschgi, M., Bieri, G., Stan, T. M., Fainberg, N., Ding, Z., Eggel, A., et al. (2011) · Nature · doi:10.1038/nature10357 · Cited by 1,763 · cited 2×
“Conversely, exposing a young mouse to an old systemic environment can inhibit myogenesis (Brack et al., 2007) and neurogenesis (Villeda et al., 2011) in the young mouse.”
Aptamer-Based Multiplexed Proteomic Technology for Biomarker Discovery
Gold, L., Ayers, D., Bertino, J., Bock, C., Bock, A., Brody, E. N., Carter, J., Dalby, A. B., Eaton, B. E., Fitzwater, T., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015004 · Cited by 1,754 · cited 1×
“The SOMAmer quantity is measured by hybridization to microarrays (for a full description, see Gold et al., 2010).”
Self-citationHaematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium
Balsam, L. B., Wagers, A. J., Christensen, J. L., Kofidis, T., Weissman, I. L., & Robbins, R. C. (2004) · Nature · doi:10.1038/nature02460 · Cited by 1,737 · cited 2×
“…solely through their common circulation, parabiosis is a powerful model to determine whether circulating factors can alter tissue function (Balsam et al., 2004; Brack et al., 2007; Conboy et al., 2005; Eggan et al., 2006; Ruckh et al., 2012; Sherwood et al., 2004; Villeda et al., 2011;…”
Self-citationIncreased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis
Brack, A. S., Conboy, M. J., Roy, S., Lee, M., Kuo, C. J., Keller, C., & Rando, T. A. (2007) · Science · doi:10.1126/science.1144090 · Cited by 1,564 · cited 4×
“Conversely, exposing a young mouse to an old systemic environment can inhibit myogenesis (Brack et al., 2007) and neurogenesis (Villeda et al., 2011) in the young mouse.”
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Liu, X., Zhang, Y., Deng, Y., Yang, L., Ou, W., Xie, M., Ding, L., Jiang, C., Yu, H., Li, Q., et al. (2022) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2021.12.015 · Cited by 63
Fan, J., Fan, J., & Khanzada, Z. (2025) · Muscles · doi:10.3390/muscles4030026 · Cited by 65
“For example, inhibition of aberrant WNT signaling reduces fibrosis and restores satellite cell function in aged muscle, while activation of Notch signaling or supplementation with WISP1 promotes regenerative capacity [310–313].”
The Mechanism of Stem Cell Aging
Mi, L., Hu, J., Li, N., Gao, J., Huo, R., Peng, X., Zhang, N., Liu, Y., Zhao, H., Liu, R., et al. (2022) · Stem Cell Reviews and Reports · doi:10.1007/s12015-021-10317-5 · Cited by 64
“Growth differentiation factor 11 can improve the function of satellite cells and NSCs, and its level will also decrease after aging [131, 132].”
BackgroundThe Fountain of Youth: A tale of parabiosis, stem cells, and rejuvenation
Conese, M., Carbone, A., Beccia, E., & Angiolillo, A. (2017) · Open Medicine · doi:10.1515/med-2017-0053 · Cited by 65
“Wagers, published another work by which they demonstrated using the parabiosis model, that age-related cardiac hypertrophy can be reversed by exposure to a young circulatory environment with only 4 weeks of parabiosis [28].”
BackgroundResultInfluentialHarper, S. C., Johnson, J. P., Borghetti, G., Zhao, H., Wang, T., Wallner, M., Kubo, H., Feldsott, E. A., Yang, Y., Joo, Y., et al. (2018) · Circulation Research · doi:10.1161/circresaha.118.312955 · Cited by 63
The nematode Caenorhabditis elegans as a model for aging research
Mack, H. I. D., Heimbucher, T., & Murphy, C. T. (2018) · Drug Discovery Today Disease Models · doi:10.1016/j.ddmod.2018.11.001 · Cited by 68
Fight to the bitter end: DNA repair and aging
Chen, Y., Geng, A., Zhang, W., Qian, Z. Y., Wan, X., Jiang, Y., & Mao, Z. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101154 · Cited by 63
Molecular pathology endpoints useful for aging studies
Niedernhofer, L. J., Kirkland, J. L., & Ladiges, W. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.012 · Cited by 59
Cellular Mechanisms of Somatic Stem Cell Aging
Jung, Y., & Brack, A. S. (2014) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-416022-4.00014-7 · Cited by 63
“, 2005), heart (Loffredo et al., 2013), and the central nervous system (Ruckh et al.”
BackgroundImpact of aging immune system on neurodegeneration and potential immunotherapies
Liang, Z., Zhao, Y., Ruan, L., Zhu, L., Jin, K., Zhuge, Q., Su, D., & Zhao, Y. L. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.07.006 · Cited by 64
Ma, J., Zhang, L., Niu, T., Ai, C., Jia, G., Jin, X., Wen, L., Zhang, K., Zhang, Q., & Li, C. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.02.011 · Cited by 59
Heart Failure with Preserved Ejection Fraction: Current Understandings and Challenges
Andersen, M. J., & Borlaug, B. A. (2014) · Current Cardiology Reports · doi:10.1007/s11886-014-0501-8 · Cited by 59
GDF11 improves tubular regeneration after acute kidney injury in elderly mice
Zhang, Y., Li, Q., Liu, D., Huang, Q., Cai, G., Cui, S., Sun, X., & Chen, X. (2016) · Scientific Reports · doi:10.1038/srep34624 · Cited by 58
Growth Differentiation Factor 11 Promotes Neurovascular Recovery After Stroke in Mice
Lu, L., Bai, X., Cao, Y., Luo, H., Yang, X., Kang, L., Shi, M.-J., Fan, W., & Zhao, B. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00205 · Cited by 57
“Initial studies showed that the serum levels of GDF11 declined with age and exogenous rGDF11 treatment could reverse the agerelated dysfunction in skeletal muscle, heart and brain through rejuvenating stem cells, suggesting that GDF11 is one of the antiaging factors (Loffredo et al., 2013; Katsimpardi et al., 2014; Si…”
BackgroundGDF11 and the Mythical Fountain of Youth
Brun, C. E., & Rudnicki, M. A. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.009 · Cited by 59
Myostatin induces interstitial fibrosis in the heart via TAK1 and p38
Biesemann, N., Mendler, L., Sawa Kostin, D., Wietelmann, A., Borchardt, T., & Braun, T. W. (2015) · Cell and Tissue Research · doi:10.1007/s00441-015-2139-2 · Cited by 58
Inhibition of Cardiomyocyte Hypertrophy by Protein Arginine Methyltransferase 5
Chen, M., Yi, B., & Sun, J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.577494 · Cited by 57
“Interestingly, the expression of PRMT5 in the heart is substantially reduced in aged rats (19), thus implicating a potential role of PRMT5 in age-related heart diseases, such as cardiac hypertrophy and heart failure (20, 21).”
BackgroundMacromolecular Degradation Systems and Cardiovascular Aging
Nakayama, H., Nishida, K., & Otsu, K. (2016) · Circulation Research · doi:10.1161/circresaha.115.307495 · Cited by 56
“Recently, 1 group demonstrated that the level of growth differentiation factor 11 declines with age and that growth differentiation factor 11 plays a role in reversal of age-related cardiac hypertrophy.(168) However, the other group was unable to confirm the findings.”
ResultThe role of GDF11 in aging and skeletal muscle, cardiac and bone homeostasis
Egerman, M. A., & Glass, D. J. (2019) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2019.1610722 · Cited by 57
“…with age (Yarasheski et al. 2002; Lakshman et al. 2009; Schafer et al. 2016; Barrios-Silva et al. 2018; Kalampouka et al. 2018) and that both Loffredo et al. (2013), and Poggioli et al. (2016), were simply detecting myostatin, and not GDF11 (Loffredo et al. 2013), or GDF11/myostatin…”
BackgroundMethodResultInfluentialXie, S., Deng, Y., Pan, Y., Wang, Z., Ren, J., Guo, X., Yuan, X., Shang, J., & Liu, H. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.06.149 · Cited by 59
Garber, K. (2016) · Nature Biotechnology · doi:10.1038/nbt.3557 · Cited by 55
Recent Developments in Clinical Plasma Proteomics—Applied to Cardiovascular Research
Palstrøm, N. B., Matthiesen, R., Rasmussen, L. M., & Beck, H. C. (2022) · Biomedicines · doi:10.3390/biomedicines10010162 · Cited by 59
“Proteomic analysis of CVD animal models have traditionally been performed using mass spectrometry for the discovery of potential biomarkers, but the recent applications of both the Olink and SomaScan assay demonstrate the feasibility of discovering relevant plasma biomarkers for CVD not only in humans but in mouse mod…”
BackgroundMethodA Young Blood Environment Decreases Aging of Senile Mice Kidneys
Huang, Q., Ning, Y., Liu, D., Zhang, Y., Li, D., Zhang, Y., Yin, Z., Fu, B., Cai, G., Sun, X., et al. (2017) · The Journals of Gerontology Series A · doi:10.1093/gerona/glx183 · Cited by 56
“These studies involved the circulatory system (2,3), nervous system (4,5), muscle tissue (6), and endocrine system (7).”
BackgroundWisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells
Fernandez‐Ruiz, R., García, A., Esteban, Y., Mir-Coll, J., Serra-Navarro, B., Fontcuberta-PiSunyer, M., Broca, C., Armanet, M., Wojtusciszyn, A., Kram, V., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19657-1 · Cited by 57
Chakrabarty, A., Chakraborty, S., Bhattacharya, R., & Chowdhury, G. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.674354 · Cited by 59
Back and forth in time: Directing age in iPSC-derived lineages
Cornacchia, D., & Studer, L. (2017) · Brain Research · doi:10.1016/j.brainres.2015.11.013 · Cited by 56
“Among the circulating factors responsible for bidirectionally affecting tissue age, members of the Notch-, Wnt- and TGFβ- pathways have been implicated (Conboy et al., 2005; Brack et al., 2007; Loffredo et al., 2013).”
Stem Cell Aging in Lifespan and Disease: A State-of-the-Art Review
Sameri, S., Samadi, P., Dehghan, R., Salem, E., Hosseini, N. F., & Amini, R. (2020) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x15666200213105155 · Cited by 57
Antiaging Strategies and Remedies: A Landscape of Research Progress and Promise
Tenchov, R., Sasso, J. M., Wang, X., & Zhou, Q. A. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00532 · Cited by 62
The Bone Morphogenetic Proteins and Their Antagonists
Mulloy, B., & Rider, C. C. (2015) · Vitamins and hormones · doi:10.1016/bs.vh.2015.06.004 · Cited by 59
DeCarolis, N. A., Kirby, E. D., Wyss‐Coray, T., & Palmer, T. D. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025874 · Cited by 55
Zhang, Y., Cheng, F., Du, X., Gao, J., Xiao, X., Li, N., Li, S., & Dong, D. (2016) · Oncotarget · doi:10.18632/oncotarget.7642 · Cited by 54
“Most studies about GDF11 focused on the smad2/3 signals related to diverse physical and pathological processes [4, 28, 29].”
BackgroundProtein Engineering for Cardiovascular Therapeutics
Jay, S. M., & Lee, R. T. (2013) · Circulation Research · doi:10.1161/circresaha.113.300215 · Cited by 51
Self-citationLuo, H., Guo, Y., Liu, Y., Wang, Y., Zheng, R., Ban, Y., Peng, L., Yuan, Q., & Liu, W. (2019) · Cell Proliferation · doi:10.1111/cpr.12631 · Cited by 53
Matters of context guide future research in TGFβ superfamily signaling
Akhurst, R. J., & Padgett, R. W. (2015) · Science Signaling · doi:10.1126/scisignal.aad0416 · Cited by 52
Castillero, E., Akashi, H., Wang, C. K., Najjar, M., Ji, R., Kennel, P. J., Sweeney, H. L., Schulze, P. C., & George, I. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.12.057 · Cited by 52
“GDF11 has also been recently identified as an important circulating factor mediating cardiac remodeling [23] and skeletal muscle atrophy [24].”
BackgroundNayor, M. G., Short, M. I., Rasheed, H., Lin, H., Jonasson, C., Yang, Q., Hveem, K., Felix, J. F., Morrison, A. C., Wild, P. S., et al. (2020) · Circulation Heart Failure · doi:10.1161/circheartfailure.119.006749 · Cited by 52
Self-citationLv, J., Hu, Y., Li, L., He, Y., Wang, J., Guo, N., Fang, Y., Chen, Q., Cai, C., Tong, J., et al. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155528 · Cited by 51
Ding, B., Yang, D., Swendeman, S. L., Christoffersen, C., Nielsen, L. B., Friedman, S. L., Powell, C. A., Hla, T., & Cao, Z. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.05.024 · Cited by 52
“Organ regeneration in most vertebrates is limited by the aging process (Boon et al., 2013; Chen et al., 2016; Conboy et al., 2005; Gurtner et al., 2008; Han et al., 2018; Katsimpardi et al., 2014; Kusumbe et al., 2016; Loffredo et al., 2013; Martinod et al., 2017; Poss, 2010; Rajagopal and Stanger, 2016; Sinha et al.,…”
BackgroundMarkers of aging: Unsupervised integrated analyses of the human plasma proteome
Coenen, L., Lehallier, B., de Vries, H. E., & Middeldorp, J. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1112109 · Cited by 51
Lin, Z., Garbern, J. C., Liu, R., Li, Q., Juncosa, E. M., Elwell, H., Sokol, M. K., Aoyama, J., Deumer, U.-S., Hsiao, E., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade8513 · Cited by 51
Self-citationGulej, R., Nyúl‐Tóth, Á., Csík, B., Petersen, B., Faakye, J., Negri, S., Chandragiri, S. S., Mukli, P., Yabluchanskiy, A., Conley, S. M., et al. (2023) · GeroScience · doi:10.1007/s11357-023-01039-2 · Cited by 51
Exploring donor and product factors and their impact on red cell post-transfusion outcomes
Ning, S., Heddle, N. M., & Acker, J. P. (2017) · Transfusion Medicine Reviews · doi:10.1016/j.tmrv.2017.07.006 · Cited by 50
Zhao, Y., Qian, R., Zhang, J., Liu, F., Iqbal, K., Dai, C., & Gong, C. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00639-w · Cited by 55
Katsimpardi, L., Kuperwasser, N., Camus, C., Moigneu, C., Chiche, A., Tolle, V., Li, H., Kokovay, E., & Lledo, P. (2020) · Aging Cell · doi:10.1111/acel.13038 · Cited by 47
“One of the factors identified in parabiosis experiments was GDF11, which was shown to rejuvenate the aged brain (Katsimpardi et al., 2014), while having a broader rejuvenating effect on other peripheral aged organs, such as the muscle and heart (Loffredo et al., 2013; Sinha et al., 2014).”
BackgroundMolecular mechanisms and therapeutic interventions in sarcopenia
Park, S. S., Kwon, E., & Kwon, K. (2017) · Osteoporosis and Sarcopenia · doi:10.1016/j.afos.2017.08.098 · Cited by 52
Cardiac aging — Getting to the stem of the problem
Hariharan, N., & Sussman, M. A. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.04.008 · Cited by 48
“Diastolic heart failure manifested as heart failure with preserved ejection fraction is another hallmark of cardiac aging [36]; however whether or not it is a stem cell disease with a cure involving stem cell based therapy remains a relatively unexplored area of myocardial biology.”
BackgroundGeißler, S., Textor, M., Schmidt‐Bleek, K., Klein, O., Thiele, M., Ellinghaus, A., Jacobi, D., Ode, A., Perka, C., Dienelt, A., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.501 · Cited by 49
“heterochronic parabiosis reverses age-related cardiac hypertrophy.(20) Thus, we hypothesize that extrinsic (cell nonautonomous) aging has a higher impact on the function of”
BackgroundZhang, Y., Shao, J., Wang, Z., Yang, T., Liu, S., Liu, Y., Fan, X., & Ye, W. (2014) · Gene · doi:10.1016/j.gene.2014.12.039 · Cited by 51
“Restoring systemic GDF11 levels reverses agerelated dysfunction in mouse heart (Loffredo et al., 2013), skeletal muscle (Sinha et al.”
BackgroundMethodInfluentialNew Treatment Strategies for Alcohol-Induced Heart Damage
Fernández‐Solà, J., & Porta, A. P. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17101651 · Cited by 53
“Therefore, Mstn, as well as its analog GDF11, have anti-hypertrophic and cardio-protective mechanisms, necessary to maintain aerobic energy metabolism in adult cardiomyocytes [75].”
BackgroundOkada, Y., & Okada, M. (2019) · Molecular Biology Reports · doi:10.1007/s11033-019-05194-8 · Cited by 48
Partial Reversal of Skeletal Muscle Aging by Restoration of Normal NAD + Levels
Mendelsohn, A. R., & Larrick, J. W. (2014) · Rejuvenation Research · doi:10.1089/rej.2014.1546 · Cited by 49
Myostatin/Activin Receptor Ligands in Muscle and the Development Status of Attenuating Drugs
Rodgers, B. D., & Ward, C. W. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab030 · Cited by 111
Progress towards the ‘Golden Age’ of biotechnology
Gartland, K. M. A., Bruschi, F., Dündar, M., Gahan, P. B., Magni, M. V., & Akbarova, Y. Y. (2013) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2013.05.011 · Cited by 47
“several human and animal diseases, including recent findings of growth differentiation factor GDF11 reversing age-related cardiac hypertrophy from murine studies [9].”
BackgroundBack to the future: how human induced pluripotent stem cells will transform regenerative medicine
Svendsen, C. N. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt379 · Cited by 50
“Supporting the possibility of rejuvenation, a number of recent high profile papers have shown that simply attaching a young mouse to an old mouse can transfer factors from the blood which increase the apparent age of the young mouse while reducing the age of the old mouse (50-52).”
BackgroundYan, C., Li, N., Xiao, T., Ye, X., Fu, L., Ye, Y., Xu, T., & Yu, J. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03412-9 · Cited by 46
“BMP2 is always used as an inducer of biological mineralization and is required for repair, and the DPSC-EV can raise it as previously reported [5, 54, 55].”
Muscle aging and sarcopenia: The pathology, etiology, and most promising therapeutic targets
Grima-Terrén, M., Campanario, S., Ramírez‐Pardo, I., Cisneros, A., Hong, X., Perdiguero, E., Serrano, A. L., Isern, J., & Muñoz‐Cánoves, P. (2024) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2024.101319 · Cited by 52
Droujinine, I. A., & Perrimon, N. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00082 · Cited by 48
“For example, GDF-11 is a BMP ligand which slows myocardial aging through unknown mechanisms (Loffredo et al., 2013).”
BackgroundSimilar sequences but dissimilar biological functions of GDF11 and myostatin
Suh, J., & Lee, Y. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00516-4 · Cited by 46
Zhang, Y., Cheng, F., Du, X., Gao, J., Xiao, X., Li, N., Li, S., & Dong, D.-L. (2016) · Oncotarget · doi:10.18632/oncotarget.10664 · Cited by 46
Mechanisms involved in hematopoietic stem cell aging
Fujino, T., Asada, S., Goyama, S., & Kitamura, T. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04356-5 · Cited by 49
Gerardo‐Ramírez, M., Lazzarini-Lechuga, R. C., Hernández-Rizo, S., Jiménez-Salazar, J. E., Nieves, A. S., García‐Ruiz, C., Fernández-Checa, J. C., Marquardt, J. U., Coulouarn, C., Gutiérrez‐Ruíz, M. C., et al. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.03.003 · Cited by 48
“While some groups report that GDF11 expression reduces with age, and its restoration induces proliferation and differentiation of progenitor cells (satellite cells) in the skeletal [9] and cardiac muscle [10], reversing the age-related hypertrophy, others state that GDF11 significantly inhibits muscle regeneration and…”
BackgroundHudobenko, J., Ganesh, B. P., Jiang, J., Mohan, E. C., Lee, S., Sheth, S. A., Morales‐Scheihing, D., Zhu, L., Kofler, J., Pautler, R. G., et al. (2020) · Aging · doi:10.18632/aging.103122 · Cited by 45
“We found that brain GDF11/8 levels decreased with age in mice, which is consistent with others that showed a tissue-specific GDF11 decline with age [3, 7, 9].”
BackgroundResultSkin Immunomodulation during Regeneration: Emerging New Targets
Mazini, L., Rochette, L., Hamdan, Y., & Malka, G. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11020085 · Cited by 45
“The exosomes released in their secretome or conditioned media improve recipient cells secretion of ECM proteins including collagen and elastin deposition [25,26,59,74,75].”
BackgroundCardiac System during the Aging Process
Fernandes-Ribeiro, A. S., Zerolo, B. E., López‐Espuela, F., Sanchez, R., & Fernandes, V. S. (2023) · Aging and Disease · doi:10.14336/ad.2023.0115 · Cited by 57
“In fact, AMPK plays a cardioprotective effect in myocardial ischemia, diabetic cardiac injury, and angiogenesis through reparative fibrosis [85,89,90].”
BackgroundSchranz, D., Akintuerk, H., & Voelkel, N. F. (2016) · Heart · doi:10.1136/heartjnl-2015-309110 · Cited by 44
Gedik, N., Kottenberg, E., Thielmann, M., Frey, U. H., Jakob, H. G., Peters, J., Heusch, G., & Kleinbongard, P. (2017) · Scientific Reports · doi:10.1038/s41598-017-12833-2 · Cited by 44
Blood-Based Therapies to Combat Aging
Castellano, J. M. (2018) · Gerontology · doi:10.1159/000492573 · Cited by 46
The influence of GDF11 on brain fate and function
Schafer, M. J., & LeBrasseur, N. K. (2019) · GeroScience · doi:10.1007/s11357-019-00054-6 · Cited by 39
Growth differentiation factor 11 supports migration and sprouting of endothelial progenitor cells
Finkenzeller, G., Stark, G. B., & Strassburg, S. (2015) · Journal of Surgical Research · doi:10.1016/j.jss.2015.05.001 · Cited by 42
Lamar, K., Bogdanovich, S., Gardner, B. B., Gao, Q. Q., Miller, T. A., Earley, J. U., Hadhazy, M., Vo, A. H., Wren, L. M., Molkentin, J. D., et al. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006019 · Cited by 43
“In several recent papers GDF11 was suggested to be a rejuvenating factor for aged skeletal muscle, although this result has not been consistently observed [9, 10, 38].”
BackgroundResultGDF11 Inhibits Bone Formation by Activating Smad2/3 in Bone Marrow Mesenchymal Stem Cells
Lu, Q., Tu, M., Li, C., Zhang, L., Jiang, T., Liu, T., & Luo, X. (2016) · Calcified Tissue International · doi:10.1007/s00223-016-0173-z · Cited by 43
Youthful systemic milieu alleviates renal ischemia-reperfusion injury in elderly mice
Liu, D., Lun, L., Huang, Q., Ning, Y., Zhang, Y., Wang, L., Yin, Z., Zhang, Y., Xia, L., Yin, Z., et al. (2018) · Kidney International · doi:10.1016/j.kint.2018.03.019 · Cited by 44
Lu, B., Zhong, J., Pan, J., Yuan, X., Ren, M., Jiang, L., Yang, Y., Zhang, G., Liu, D., & Zhang, C. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-02166-1 · Cited by 44
Cancer-Associated Cachexia: A Systemic Consequence of Cancer Progression
Biswas, A., & Acharyya, S. (2019) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030419-033642 · Cited by 42
“The role of GDF11 in aging-relatedmuscle regeneration has been controversial (Egerman et al. 2015, Loffredo et al. 2013, Sinha et al. 2014).”
BackgroundWang, L., Xie, L., Tintani, F., Xie, H., Li, C., Cui, Z., Wan, M., Zu, X., Qi, L., & Cao, X. (2016) · Stem Cells Translational Medicine · doi:10.5966/sctm.2015-0411 · Cited by 41
Sarkar, S. N., Russell, A. E., Engler-Chiurazzi, E. B., Porter, K. N., & Simpkins, J. W. (2018) · Aging and Disease · doi:10.14336/ad.2018.0409 · Cited by 43
“potential to regenerate and function analogous to juvenile tissues [7-10].”
BackgroundRestoring aged stem cell functionality: Current progress and future directions
Spehar, K., Pan, A., & Beerman, I. (2020) · Stem Cells · doi:10.1002/stem.3234 · Cited by 46
Chen, M., Li, Y., Lv, H., Yin, P., Zhang, L., & Tang, P. (2020) · Journal of Proteomics · doi:10.1016/j.jprot.2020.103940 · Cited by 41
Jarvis, T. C., Davies, D. R., Hisaminato, A., Resnicow, D. I., Gupta, S., Waugh, S. M., Nagabukuro, A., Wadatsu, T., Hishigaki, H., Gawande, B. N., et al. (2015) · Structure · doi:10.1016/j.str.2015.03.027 · Cited by 41
Senarath-Yapa, K., McArdle, A., Renda, A., Longaker, M. T., & Quarto, N. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15069314 · Cited by 42
“Further studies need to be carried out in ASCs to identify pathways regulating their aged program as it may have implications for their use in cell therapies for skeletal pathology [95,96].”
BackgroundJin, Q., Qiao, C., Li, J., Xiao, B., Li, J., & Xiao, X. (2019) · Skeletal Muscle · doi:10.1186/s13395-019-0197-y · Cited by 42
Mehdipour, M., Etienne, J., Chen, C.-C., Gathwala, R., Rehman, M., Kato, C., Liu, C., Liu, Y., Zuo, Y., Conboy, M. J., et al. (2019) · Aging · doi:10.18632/aging.102148 · Cited by 39
“Experiments in mice showed this shared circulatory milieu restored tissue health and regeneration of the old partner; and at the same time, the young partner experienced a regenerative decline in a number of tissues [1-5].”
BackgroundAnti-Aging Effects of GDF11 on Skin
Rochette, L., Mazini, L., Méloux, A., Zeller, M., Cottin, Y., Vergely, C., & Malka, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072598 · Cited by 41
“Its expression is at the highest level in young adult organs and seems to decline during aging [33].”
BackgroundIt’s in Our Blood: A Glimpse of Personalized Medicine
Lamb, J. R., Jennings, L. L., Guðmundsdóttir, V., Gudnason, V. G., & Emilsson, V. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.09.003 · Cited by 37
The versatility and paradox of GDF 11
Jamaiyar, A., Wan, W., Janota, D., Enrick, M., Chilian, W. M., & Yin, L. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.032 · Cited by 44
“In a mouse model of heterochronic parabiosis, GDF 11 was determined to be the circulating factor in the blood of younger mice that reversed age-related cardiac hypertrophy in older mice (Loffredo et al., 2013).”
Mid-old cells are a potential target for anti-aging interventions in the elderly
Kim, Y. H., Lee, Y., Park, S. S., Park, S. H., Eom, S. Y., Lee, Y., Lee, W. J., Jang, J., Seo, D., Kang, H. Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43491-w · Cited by 44
Cardiac ageing: from hallmarks to therapeutic opportunities
Hastings, M. H., Zhou, Q., Wu, C., Shabani, P., Huang, S., Yu, X., Singh, A. P., Guseh, J. S., Li, H., Lerchenmüller, C., et al. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae124 · Cited by 42
Quality control systems in cardiac aging
Quarles, E. K., Dai, D., Tocchi, A., Basisty, N., Gitari, L., & Rabinovitch, P. S. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.02.003 · Cited by 42
Stress Signaling Between Organs in Metazoa
Owusu-Ansah, E., & Perrimon, N. (2015) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100814-125523 · Cited by 39
“The importance of secretory factors in modulating cardiac physiology has also been shown in a study in which cardiomyocyte hypertrophy was reversed as a result of exposure to humoral factors fromyoungmice (Loffredo et al. 2013).”
BackgroundLi, X., Zhou-long, Z., & Wang, H. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.06.002 · Cited by 40
Wang, Y., Guo, Y., Fu, G., Guan, C., Zhang, X., Yang, D. G., & Shi, Y. C. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01792-7 · Cited by 40
Meng, F., Wang, G., Zhou, F., Li, G., Wang, M., Zhou, Z., Han, Y., Chen, X., Hu, Y., Zhang, Y., et al. (2024) · Composites Part B Engineering · doi:10.1016/j.compositesb.2024.111358 · Cited by 40
Ikemoto‐Uezumi, M., Uezumi, A., Tsuchida, K., Fukada, S., Yamamoto, H., Yamamoto, N., Shiomi, K., & Hashimoto, N. (2015) · Stem Cells · doi:10.1002/stem.2045 · Cited by 39
Lack of Cardiac Improvement After Cardiosphere-Derived Cell Transplantation in Aging Mouse Hearts
Zhao, Z., Han, X., Lei, W., Li, J., Yang, Z., Wu, J., Yao, M.-C., Lu, X., He, L., Chen, Y., et al. (2018) · Circulation Research · doi:10.1161/circresaha.118.313005 · Cited by 37
Signal Transduction, Ageing and Disease
Zhang, L. J., Yousefzadeh, M. J., Suh, Y., Niedernhofer, L. J., & Robbins, P. D. (2019) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-3681-2_9 · Cited by 40
Circulating plasma factors involved in rejuvenation
Kang, J. S., & Yang, Y. R. (2020) · Aging · doi:10.18632/aging.103933 · Cited by 39
“that a previously used GDF11 SOMAmer and GDF11 antibodies bind to both GDF11 and myostatin [11, 12, 100], and GDF11-specific immunoassays revealed that”
BackgroundMethodInfluentialConcise Review: Hematopoietic Stem Cell Aging and the Prospects for Rejuvenation
Wahlestedt, M., Pronk, C. J., & Bryder, D. (2014) · Stem Cells Translational Medicine · doi:10.5966/sctm.2014-0132 · Cited by 38
Small Molecules Targeting in Vivo Tissue Regeneration
Längle, D. S., Halver, J., Rathmer, B., Willems, E., & Schade, D. (2013) · ACS Chemical Biology · doi:10.1021/cb4008277 · Cited by 40
Shafei, A., ALI, M. A. M., Ghanem, H. G., Shehata, A. I., Abdelgawad, A. A., Handal, H. R., ElSayed, A. S., Ashaal, A. E., Ali, M. M., & El‐Shal, A. S. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26637 · Cited by 38
“Growth differentiation factor-11 (GDF11), a circulating protein that was revealed as a rejuvenating factor for the aging heart by parabiosis experiments, actively prevents fibrosis following myocardial injury.(57) Noteworthy, both MSCs and CD34+ cells exert a protective effect against the structural damaging effect of…”
BackgroundInterventions to restore appropriate immune function in the elderly
Aspinall, R., & Lang, P. O. (2018) · Immunity & Ageing · doi:10.1186/s12979-017-0111-6 · Cited by 39
“cardiac system [36] and in cognitive function [37].”
Background
Metadata
- Authors
- Loffredo, F. S., Steinhauser, M. L., Jay, S. M., Gannon, J., Pancoast, J. R., Yalamanchi, P., Sinha, M., Dall’Osso, C., Khong, D., Shadrach, J. L., Miller, C. M., Singer, B. S., Stewart, A., Psychogios, N., Gerszten, R. E., Hartigan, A. J., Kim, M.-J., Serwold, T., Wagers, A. J., & Lee, R. T.
- Affiliations
- Brigham and Women's Hospital (US)
- SomaLogic (United States) (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Wagers, Amy J.
- Lee, Richard T.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 153
- Issue
- 4
- Pages
- 828-839
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3677132
- OpenAlex
- W2156589853
- Cited by
- 948
- References
- 64
- Citations by year
- 2026: 44 · 2025: 46 · 2024: 53 · 2023: 67 · 2022: 69 · 2021: 69 · 2020: 87 · 2019: 70 · 2018: 86 · 2017: 91 · 2016: 94 · 2015: 84 · 2014: 56 · 2013: 30
- FWCI
- 59.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- American Heart Association
- National Institutes of Health (1dp2od004345-01)
- Harvard Stem Cell Institute
- National Institute on Aging (R01AG033053, R01AG032977, R01AG040019)
- National Heart, Lung, and Blood Institute (U01HL100402, K99HL112905, R00HL112905)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK090147, P30DK036836)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- GDF11, cardiac hypertrophy, cardiac aging, heterochronic parabiosis, circulating factors, heart failure with preserved ejection fraction, cardiomyocyte size, TGF-beta superfamily, aptamer-based proteomics, regenerative therapy
- MeSH terms
- Aging, Animals, Blood Pressure, Female, Cardiomegaly, Humans, Male, Mice, Inbred C57BL, Parabiosis, Hypertrophy, Left Ventricular, Bone Morphogenetic Proteins, Myocytes, Cardiac, Mice, Forkhead Transcription Factors, Growth Differentiation Factors, Induced Pluripotent Stem Cells
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