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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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InfluentialSelf-citationThe ageing systemic milieu negatively regulates neurogenesis and cognitive function
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Self-citationIncreased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis
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“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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Beyond Static Pipes: Mechanisms and In Vitro Models of Vascular AgingPreprint
Hetzer, M. W., & Bersini, S. (2022) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041180 · Cited by 10
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The Problem of Irreproducible Bioscience Research
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“…the transcription level of IL-10 anti-in fl ammatory factor and downregulating the expression of in fl ammatory factors such as IL-1 β , IL-6, and TNF-α [29]; however, it has not yet been reported whether GDF11 regulates macrophage differentiation and promotes repair in AKI induced by I/R.”
BackgroundSedentary Lifestyle and the Risk for HFpEF
Shah, S. J. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.01.010 · Cited by 10
“Based on a parabiosis model of aging, growth differentiation factor 11 has been identified as a potential circulating factor involved in cardiac hypertrophy (14).”
Native nanodiscs from blood inhibit pulmonary fibrosis
Sun, A., Lai, Z., Zhao, M., Li, M., & Hu, X. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.10.045 · Cited by 9
Circulating Concentrations of GDF11 are Positively Associated with TSH Levels in Humans
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“Initial studies suggesting a rejuvenating action for GDF11 showed that after parabiosis experiments in mice, reversal of age-related cardiac hypertrophy was due to a blood-borne factor that was attributed to GDF11 [26,27].”
BackgroundVampires 2.0? The ethical quandaries of young blood infusion in the quest for eternal life
Lavazza, A., & Garasic, M. D. (2020) · Medicine Health Care and Philosophy · doi:10.1007/s11019-020-09952-5 · Cited by 9
Serum growth differentiation factor 11 is closely related to metabolic syndrome in a Chinese cohort
Xu, B., Huang, Y., Zhang, R., Tang, M., He, Z., Jin, L., Zong, Y., Hu, C., & Jia, W. (2020) · Journal of Diabetes Investigation · doi:10.1111/jdi.13337 · Cited by 9
BMP11 regulates thermogenesis in white and brown adipocytes
Pham, H. G., Mukherjee, S., Choi, M. J., & Yun, J. W. (2021) · Cell Biochemistry and Function · doi:10.1002/cbf.3615 · Cited by 9
Suzuki, Y., Takaya, K., Watanabe, S., Otaki, M., Kono, H., & Kishi, K. (2022) · Aging · doi:10.18632/aging.203966 · Cited by 9
Decline of stress resilience in aging rats: Focus on choroid plexus-cerebrospinal fluid-hippocampus
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“Data are expressed as mean± SEM, p< 0.05, p< 0.01. promote vasculogenesis and neurogenesis in brain and reverse age-related cognitive decline (Loffredo et al. 2013).”
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Veskoukis, A. S., Paschalis, V., Kyparos, A., & Nikolaidis, M. G. (2018) · Redox Biology · doi:10.1016/j.redox.2018.01.001 · Cited by 10
Pathomechanisms of Monoallelic variants in TTN causing skeletal muscle disease
Gohlke, J., Lindqvist, J., Hourani, Z., Rich, K. A., Arnold, W. D., Heintzman, S., Tonino, P., Elsheikh, B., Morales, A., Vatta, M., et al. (2024) · Human Molecular Genetics · doi:10.1093/hmg/ddae136 · Cited by 8
“Although several high-profile reports attributed rejuvenating effects to GDF11 in heart and skeletal muscle [50,51], more recent studies show that increased levels inhibit skeletal muscle regeneration and induce striated muscle atrophy and wasting by activating SMAD2/3 and MAPK signaling pathways…”
Senescence-related myocardial dysfunction: keeping a young heart
Ajjan, R., Huckstepp, R. T. R., Akbar, N., Bauersachs, J. K., Lok, J. C. W., Choppy-Madeleine, J., Christopher, G., Dalakoti, M., Dawson-Plincke, E., Dodds, J., et al. (2026) · European Heart Journal · doi:10.1093/eurheartj/ehag095 · Cited by 11
“147 Intravenous injection of small EVs from young mice mitigates cardiac ageing by reducing cellular senescence.”
Functional replacement of myostatin with GDF-11 in the germline of mice
Lee, S., Lehar, A., Rydzik, R., Youngstrom, D. W., Bhasin, S., Liu, Y., & Germain‐Lee, E. L. (2022) · Skeletal Muscle · doi:10.1186/s13395-022-00290-z · Cited by 7
“Circulating GDF-11 levels in mice have been reported to decline during aging [75], and injection of purified GDF-11 protein to aged mice was shown to reverse age-related cardiac hypertrophy [75], stimulate vascular remodeling and enhance neurogenesis in the nervous system of aged mice [76], and improve satellite cell…”
BackgroundCawthon, P. M., Patel, S., Newman, A. B., Bhasin, S., Peng, L., Tracy, R. P., Kizer, J. R., Lee, S., Ferrucci, L., Ganz, P., et al. (2023) · The Journals of Gerontology Series A · doi:10.1093/gerona/glad045 · Cited by 10
Deficiency of GDF-11 Accelerates TAC-Induced Heart Failure by Impairing Cardiac Angiogenesis
Zhu, J., Zhang, N., Zhao, Y. F., Liu, Q., Wang, Y., Chen, M., Ma, Q., Dong, A., Wang, Y., & Yu, H. (2023) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2022.11.004 · Cited by 8
“Our data are consistent with previous studies showing that the spleen was the major source of GDF-11 in circulation.(7) All these results suggest that GDF-11 secreted from heart acts mainly locally and has less systemic effect as endocrine factors.”
ResultAhn, S.-T., Suh, S.-I., Moon, H., & Hyun, C. (2016) · PubMed Central · Cited by 8
GDF11 protein as a geroprotector
Khavinson, V. K., Bi, K., Tarnovskaya, S. I., & Linkova, N. S. (2016) · Biology Bulletin Reviews · doi:10.1134/s207908641602002x · Cited by 8
Yamagishi, S., Matsui, T., Kurokawa, Y., & Fukami, K. (2016) · BioResearch open access · doi:10.1089/biores.2016.0015 · Cited by 8
Towards cultural materialism in the medical humanities: the case of blood rejuvenation
Oakley, C. (2017) · Medical Humanities · doi:10.1136/medhum-2017-011209 · Cited by 8
“55 Speaking to the New Scientist , Amy Wagers, Professor of Stem Cell and Regenerative Biology at Harvard University, noted that since all parts of the body age at the same rate, it is conceivable that the blood has an instrumental role in the ageing process.”
BackgroundKey Age-Imposed Signaling Changes That Are Responsible for the Decline of Stem Cell Function
Mehdipour, M., Liu, Y., Liu, C., Kumar, B., Kim, D., Gathwala, R., & Conboy, I. M. (2018) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-2835-0_5 · Cited by 8
Effect of CCL11 on In Vitro Myogenesis and Its Clinical Relevance for Sarcopenia in Older Adults
Kim, D. A., Park, S. J., Lee, J. Y., Kim, J. H., Lee, S., Lee, E., Jang, I., Jung, H., Park, J. H., & Kim, B. (2021) · Endocrinology and Metabolism · doi:10.3803/enm.2020.942 · Cited by 8
“In detail, the exposure of old mice to young blood rejuvenated aged organs and tissues [10,11], whereas an exchange with old blood rapidly inhibited the physiologic functions of young mice [12].”
BackgroundSu, H.-H., Yen, J., Liao, J., Wang, Y.-H., Liu, P.-H., MacDonald, I. J., Tsai, C., Chen, Y., & Huang, S. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112290 · Cited by 8
Sills, E. S., & Wood, S. H. (2022) · Journal of Clinical and Translational Research · doi:10.18053/jctres.08.202201.008 · Cited by 7
“Such BMP-11 use in reproductive biology was a logical continuation of prior work where this intervention had already corrected age-related myocardial hypertrophy [19], improved brain capillary and muscle function [20,21], successfully deferred production of age-specific biomarkers [22], and even extended lifespan of e…”
BackgroundSong, L., Wu, F., Li, C., & Zhang, S. (2022) · Biogerontology · doi:10.1007/s10522-022-09967-w · Cited by 8
“Altogether these data provide additional evidences that GDF11 has rejuvenation activity, capable of reversing aging (Loffredo et al. 2013; Katsimpardi et al. 2014; Zhou et al. 2019a, b; Sinha et al. 2014).”
BackgroundThe Role of Blood-Derived Factors in Protection and Regeneration of Aged Tissues
Höving, A. L., Schmidt, K. E., Kaltschmidt, B., Kaltschmidt, C., & Knabbe, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179626 · Cited by 8
“However, this method did not reveal significant differences between heterochronic compared to isochronic parabiotic mice [62].”
BackgroundResultMicroRNA-96 promotes myocardial hypertrophy by targeting mTOR.
Sun, X., & Zhang, C. (2015) · PubMed Central · Cited by 8
Cellular and Molecular Biomarkers Indicate Premature Aging in Pseudoxanthoma Elasticum Patients
Tiemann, J., Wagner, T., Vanakker, O. M., Gils, M. V., Cabrera, J. L. B., Ibold, B., Faust, I., Knabbe, C., & Hendig, D. (2020) · Aging and Disease · doi:10.14336/ad.2019.0610 · Cited by 10
“specifity and selectivity of detection methods and to potential low overall GDF11 serum concentration [24, 33, 42-44].”
BackgroundInfluentialGaudilliere, B. L., Xue, L., Tsai, A. S., Gao, X., McAllister, T. N., Tingle, M. S., Porras, G., Feinstein, I., Feyaerts, D., Verdonk, F., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06215-w · Cited by 7
GDF11 Regulates M1 and M2 Polarization of BV2 Microglial Cells via p38 MAPK Signaling Pathway
Zhao, X., Qin, R., Li, G., Lv, G., Zhao, D., Kong, L., Qi, M., & Li, P. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04837-1 · Cited by 7
“Initial studies suggested that GDF11 is capable of reversing the progression of cardiac hypertrophy with age, improving skeletal muscle function, and enhancing neurogenesis, leading to the notion that GDF11 might be a “fountain of youth” molecule [7, 8].”
The promise of organ rejuvenation to overcome the shortage in organ transplantation
Kayumov, M., Song, Z., Martin, F., Tsou, S., Xiao, Y., Zhou, H., & Tullius, S. G. (2025) · Nature Communications · doi:10.1038/s41467-025-66133-9 · Cited by 7
“HCTx suggests three key mechanisms that may carry rejuvenative/aging effects: components related to the TGF-β signaling pathway, have been shown to play a critical role for rejuvenation 115 .”
Song, Z., Hu, H., Zhang, W., Zheng, X., Liang, L., Zhao, B., Song, G., Li, J., Li, S., Wen, Y., et al. (2026) · Nature Aging · doi:10.1038/s43587-026-01087-1 · Cited by 7
Growth differentiation factor 11: A proangiogenic drug as a potential antiaging regulating molecule
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Heart Failure with Preserved Ejection Fraction (HFpEF)
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Kizer, J. R., Patel, S., Ganz, P., Newman, A. B., Bhasin, S., Lee, S., Cawthon, P. M., LeBrasseur, N. K., Shah, S. J., Psaty, B. M., et al. (2023) · The Journals of Gerontology Series A · doi:10.1093/gerona/glad206 · Cited by 7
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“Another potential new application of the parabiotic hypoxic/ normoxic model is to investigate the interaction between oxygenation and aging: demyelinating diseases (25), cognitive function impairments and synaptic plasticity (31), muscle loss (29), or cardiac hypertrophy (20).”
BackgroundMethodYang, Y., Yang, Y., Wang, X., Du, J., Hou, J., Feng, J., Tian, Y., He, L., Li, X., & Pei, H. (2016) · Journal of International Medical Research · doi:10.1177/0300060516658984 · Cited by 7
“In addition, GDF11 levels exhibit an agedependent decline in both the spleen and the general circulation.(11) It is well known that ageing is one of the main risk factors for IHD and cardiac hypertrophy.”
BackgroundInfluentialFunctional similarities of microRNAs across different types of tissue stem cells in aging
Watanabe, K., Ikuno, Y., Kakeya, Y., Kito, H., Matsubara, A., Kaneda, M., Katsuyama, Y., & Naka-Kaneda, H. (2018) · Inflammation and Regeneration · doi:10.1186/s41232-018-0066-9 · Cited by 7
Growth Differentiation Factor-11 Causes Neurotoxicity During Ischemia in vitro
Sutherland, B. A., Hadley, G., Alexopoulou, Z., Lodge, T., Neuhaus, A. A., Couch, Y., Kalajian, N. Y., Morten, K., & Buchan, A. M. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.01023 · Cited by 7
“Circulating GDF-11 levels have been shown to decrease with age (4, 6, 19), though this is controversial (5, 20), but this could leave the brain in a susceptible state.”
BackgroundSkeletal stem cells and their contribution to skeletal fragility: senescence and rejuvenation
Aldahmash, A. M. (2015) · Biogerontology · doi:10.1007/s10522-015-9623-7 · Cited by 8
“Growth differentiation factor 11 (GDF11) has been suggested to play a role, as a youthful factor (Loffredo et al. 2013).”
BackgroundShort Peptides and Telomere Length Regulator Hormone Irisin
Khavinson, V. K., Bi, K., Tarnovskaya, S. I., & Linkova, N. S. (2016) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-016-3167-y · Cited by 7
Replacement as an aging intervention
Lore, S., Poganik, J. R., Atala, A., Church, G. M., Gladyshev, V. N., Scheibye‐Knudsen, M., & Verdin, E. M. (2025) · Nature Aging · doi:10.1038/s43587-025-00858-6 · Cited by 6
“Beyond muscle tissue, HPB has improved function in the liver 27 , the central nervous system 29 , bone 26 , the heart (hypertrophy) 30 and the brain (Alzheimer’s disease) 31 .”
The rosetta stone of successful ageing: does oral health have a role?
Poser, M., Sing, K. E. A., Ebert, T., Ziebolz, D., & Schmalz, G. (2023) · Biogerontology · doi:10.1007/s10522-023-10047-w · Cited by 7
“Altering intercellular communications will be an important target for potential interventions (Wang et al. 2021a; Piper et al. 2011; Sanchez-Roman et al. 2012; Loffredo et al. 2013).”
BackgroundThe regulatory effect of growth differentiation factor 11 on different cells
Shao, Y., Liu, T., Wen, X., Zhang, R., Liu, X., & Xing, D. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1323670 · Cited by 6
Therapeutic targeting of GDF11 in muscle atrophy: Insights and strategies
Wang, C., Liu, X., Hu, X., Wu, T., & Duan, R. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.135321 · Cited by 6
Extracellular Vesicles in Aging and Age‐Related Diseases. How Important Are They?
Lundy, D. J., & Liao, C. (2025) · Advanced Biology · doi:10.1002/adbi.202400656 · Cited by 7
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Wang, D.-X., Zhu, X., Ma, X.-R., Wang, L., Dong, Z.-J., Lin, R., Cao, Y., & Zhao, J. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.726345 · Cited by 6
Pregnancy, a unique case of heterochronic parabiosis and peripartum cardiomyopathy
Goldschmidt‐Clermont, P. J., Hubinont, C., Goldschmidt, A. J. P., DiFede, D. L., & White, I. A. (2021) · Frontiers in Bioscience-Landmark · doi:10.52586/4975 · Cited by 6
“[27] showed the heterochronic parabiosis can prevent age related cardiac hypertrophy.”
BackgroundMethodMultifaceted Benefits of GDF11 Treatment in Spinal Cord Injury: In Vitro and In Vivo Studies
Tsai, M., Fay, L.-Y., Liou, D.-Y., Chen, Y., Chen, Y.-T., Lee, M., Tu, T.-H., Huang, W., & Cheng, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010421 · Cited by 6
“[10] pointed out that GDF11 is a member of the activin subfamily, capable of activating the Smad2/3 signaling pathway.”
BackgroundCai, A., Schneider, P., Zheng, Z., Beier, J. P., Himmler, M., Schubert, D. W., Weisbach, V., Horch, R. E., & Arkudas, A. (2023) · BMC Molecular and Cell Biology · doi:10.1186/s12860-023-00478-1 · Cited by 6
“Growth differentiation factor 11 (GDF11), a member of the transforming growth factor (TGF)-beta superfamily [14], has shown beneficial effects on skeletal muscle regeneration, restoring satellite cell regenerative function in aged muscle cells and mice [15] and was identified as a rejuvenation factor in heterochronic…”
BackgroundWu, Z., Zhang, L., Jia, Y., Bi, B., Fang, L., & Cheng, J. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01201-5 · Cited by 6
Mutual regulation between GDF11 and TET2 prevents senescence of mesenchymal stem cells
Gao, J., Wang, H., Shen, J., Liu, X., Zhu, X., Zhao, E., Li, G., Sun, Y., Yin, F., Liu, Z., et al. (2023) · Journal of Cellular Physiology · doi:10.1002/jcp.31132 · Cited by 7
“…antiaging effect in old animals during parabiosis or whether GDF11 has any antiaging effect, has been heavily debated (Egerman et al., 2015; Katsimpardi et al., 2014; Loffredo et al., 2013; Olson et al., 2015; Poggioli et al., 2016; Sinha et al., 2014; Smith et al., 2015; Walker et al., 2017).”
BackgroundBuigues, A., Ramírez-Martín, N., Martínez, J., Pellicer, N., Meseguer, M., Pellicer, A., & Herraiz, S. (2023) · Aging · doi:10.18632/aging.205400 · Cited by 6
“AGING blood from younger individuals can reverse some aspects and clinical signs of aging [9, 14–16].”
BackgroundWei, S.-Y., Chou, Y., Chang, F., Huang, S., Lai, C., & Lin, S. (2024) · Aging and Disease · doi:10.14336/ad.2023.1230 · Cited by 7
Rejuvenation of the Aging Heart: Molecular Determinants and Applications
Alibhai, F. J., & Li, R. (2024) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2024.03.004 · Cited by 6
Chiao, Y. A. (2013) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.113.000277 · Cited by 6
Young blood rejuvenates old brains
Paul, S. M., & Reddy, K. (2014) · Nature Medicine · doi:10.1038/nm.3597 · Cited by 6
New platform for cataloging hundreds of proteins gets test drive
Powell, K. (2014) · Nature Medicine · doi:10.1038/nm1014-1082 · Cited by 6
Goldstein, J. M., Valido, A., Lewandowski, J. P., Walker, R. G., Mills, M. J., Messemer, K. A., Besseling, P. J., Lee, K. H., Wattrus, S. J., Cho, M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-54766-y · Cited by 5
Self-citationLiu, W., Zhou, L., Xue, H., Li, H., & Yuan, Q. (2020) · Journal of Periodontology · doi:10.1002/jper.19-0247 · Cited by 6
Intense light as anticoagulant therapy in humans
Oyama, Y., Shuff, S. R., Davizon‐Castillo, P., Clendenen, N., & Eckle, T. D. L. G. (2020) · PLoS ONE · doi:10.1371/journal.pone.0244792 · Cited by 6
Novel Biomarkers to Understand Cardiovascular Complications in Diabetes
Adela, R., & Banerjee, S. K. (2016) · InTech eBooks · doi:10.5772/62595 · Cited by 6
“GDF-11 levels reversed the age-related hypertrophied heart into a young heart [52].”
BackgroundӦzcan, I., Toya, T., Corban, M., Ahmad, A., Loeffler, D. L., Morse, D. W., Lerman, L. O., Kushwaha, S. S., & Lerman, A. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab203 · Cited by 6
Posttranslational Processing of Secretory Proteins
Seidah, N. G., & Guillemot, J. (2016) · Wiley eBooks · doi:10.1002/9781118760369.ch9 · Cited by 6
Cai, A., Schneider, P., Zheng, Z., Beier, J. P., Himmler, M., Schubert, D. W., Weisbach, V., Horch, R. E., & Arkudas, A. (2022) · Research Square · doi:10.21203/rs.3.rs-1225911/v1 · Cited by 6
Aluri, S., Ling, T., Fraint, E., Chakraborty, S., Zhang, K. X., Ahsan, A., Kravets, L., Poigaialwar, G., Zhao, R., Pradhan, K., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci189266 · Cited by 5
“Immunoblotting confirmed that a greater relative proportion of GATA1s was produced in human primary erythroid progenitors upon GDF11 stimulation; aging, but its role in regulating human hematopoiesis has not been well defined (10–12).”
Research progress on blood therapy for anti-aging
Liu, S., Wang, S., Dong, Y., Yang, S., & Yao, C. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.07.039 · Cited by 5
“HPB was found to significantly reduce mice cardiac hypertrophy and diminish cardiomyocyte size [91–93].”
Erythropoiesis in health and disease: Distinguishing defective and ineffective erythropoiesis
Hoss, S. E., Lizarralde-Iragorri, M. A., Maciel, T. T., & Hermine, O. (2026) · HemaSphere · doi:10.1002/hem3.70297 · Cited by 8
“41,42 These multifaceted effects underscore how IE is central to the pathology of β ‐ thalassemia, with both the anemia and its associated complications arising from the unchecked production and death of erythroid precursors.”
The disparity of platelet factor 4 and platelets in individuals of different ages
Weng, R., Liu, J., Yu, Q., Yuan, H., Qiu, Y., Liu, H., Wang, L., Mei, Z., & Zhu, F. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e34923 · Cited by 6
Potential role of recombinant growth differentiation factor 11 in Alzheimer’s disease treatment
de Liyis, B. G., Halim, W., & Widyadharma, I. P. E. (2022) · The Egyptian Journal of Neurology Psychiatry and Neurosurgery · doi:10.1186/s41983-022-00487-5 · Cited by 5
“Interestingly, new findings have proven the regenerative factors of GDF11 in the brain [13], heart [14], skeletal muscle [15], kidney [16], bone [17], and skin [18].”
BackgroundGDF11 Is a Novel Protective Factor Against Vascular Calcification
Sheng, Y., Zhang, C., Liu, Y., Xu, B., Jin, T., Ye, T., Liu, J., Wu, G., Chen, L., & Zong, G. (2022) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000001357 · Cited by 5
GDF11 reverses mood and memory declines in aging
Piantadosi, P. T., & Holmes, A. (2023) · Nature Aging · doi:10.1038/s43587-023-00362-9 · Cited by 5
The secretome as a biomarker and functional agent in heart failure
Nyarko, O. O., & Sucharov, C. C. (2023) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2023.15 · Cited by 5
“GDF-11 exerts antihypertrophic effects in young mice and its levels are decreased with increasing age[57].”
BackgroundLi, M., Liu, J.-X., Ma, B., Liu, J., Chen, J., Jin, F., Hu, C., Xu, H., Zheng, C., & Hou, R. (2024) · Stem Cell Reviews and Reports · doi:10.1007/s12015-024-10710-w · Cited by 5
“Cellular secretions, in respect of systemic and local paracrine factors such as hormones [56], cytokines [57], chemo-kines [16] and exosomes [18 ], exert significant influences on tissue and organ homeostasis.”
Whole-Genome Resequencing Reveals Genetic Diversity and Growth Trait-Related Genes in Pinan Cattle
Bo, D., Feng, Y., Bai, Y., Li, J., Wang, Y., You, Z., Shen, J., & Bai, Y. (2024) · Animals · doi:10.3390/ani14152163 · Cited by 5
“The growth differentiation factor 11 ( GDF11 ) gene is a member of the TGF-β superfamily, and studies have revealed its importance in regulating the development of the nervous and organ systems, the regeneration of muscle and bone [38], and the health of the cardiovascular system [39].”
BackgroundThe non-canonical Wnt pathway leads to aged dendritic cell differentiation
Zhou, H., & Wu, L. (2018) · Cellular and Molecular Immunology · doi:10.1038/cmi.2017.169 · Cited by 5
Yang, V. K., Rush, J. E., Bhasin, S., Wagers, A. J., & Lee, R. T. (2019) · Journal of Veterinary Cardiology · doi:10.1016/j.jvc.2019.08.002 · Cited by 5
“This response to GDF11 treatment raises the possibility that levels of circulating GDF11 and/or GDF8 are related to the degree of cardiac hypertrophy [4].”
BackgroundMethodResultInfluentialSelf-citationΓουτιάνος, Γ., Margaritelis, N. V., Sparopoulou, T., Veskoukis, A. S., Vrabas, I. S., Paschalis, V., Nikolaidis, M. G., & Kyparos, A. (2020) · The Journal of Physiological Sciences · doi:10.1186/s12576-020-00737-2 · Cited by 6
Oyama, Y., Shuff, S. R., Maddry, J. K., Schauer, S. G., Bebarta, V. S., & Eckle, T. D. L. G. (2020) · Military Medicine · doi:10.1093/milmed/usaa088 · Cited by 5
Eosinophils and White Fat: Protection from Worms and Inflammaging
Larrick, J. W., & Mendelsohn, A. R. (2020) · Rejuvenation Research · doi:10.1089/rej.2020.2375 · Cited by 5
Serum-Induced Proliferation of Human Cardiac Stem Cells Is Modulated via TGFβRI/II and SMAD2/3
Schmidt, K. E., Höving, A. L., Zahrani, S. K., Trevlopoulou, K., Kaltschmidt, B., Knabbe, C., & Kaltschmidt, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25020959 · Cited by 5
“Additionally, beneficial effects of young blood, plasma or serum in old tissues and organs as well as in various stem cell populations were described [16,18].”
BackgroundGuinn, N. R., Waldron, N. H., Cooter, M. L., Goldberg, C. L., Kertai, M. D., Raghunathan, K., Bandarenko, N., Hoffman, M., & Bennett‐Guerrero, E. (2016) · Transfusion · doi:10.1111/trf.13616 · Cited by 5
The effect of aging on the bone healing properties of blood plasma
Al‐Hamed, F. S., Rodan, R., Ramírez-GarcíaLuna, J. L., Elkashty, O. A., Alshahrani, N. S., Tran, S. D., Lordkipanidzé, M., Kaartinen, M. T., Badran, Z., & Tamimi, F. (2021) · Injury · doi:10.1016/j.injury.2021.05.001 · Cited by 5
Leinwand, L. A., & Harrison, B. C. (2013) · Cell · doi:10.1016/j.cell.2013.04.038 · Cited by 5
“Here, Loffredo et al. demonstrate that exposing an old mouse to the circulation of a young mouse using a powerful technique called parabiosis can reverse many of the biological consequences of age-related cardiac hypertrophy (Loffredo et al., 2013).”
MethodMashinchian, O., Hong, X., Michaud, J., Migliavacca, E., Lefebvre, G. C., Boss, C., Franceschi, F. D., Moal, E. L., Collerette-Tremblay, J., Isern, J., et al. (2022) · eLife · doi:10.7554/elife.57393 · Cited by 5
“Freshly 649 isolated niche resident cells were isolated and transcriptomically analyzed as previously 650 described (Lukjanenko et al., 2016).”
MethodActivated GDF11/8 subforms predict cardiovascular events and mortality in humans
Walker, R. G., Kato, T., Ben Driss, L., Williams, S. A., Hinterberg, M. A., Janjic, N., Gelinas, A. D., Carpenter, M. A., Kattamuri, C., Walter, J. E., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61815-w · Cited by 4
Self-citationHyaluronan and proteoglycan link protein 1 – A novel signaling molecule for rejuvenating aged skin
Fu, Z., Yang, G., Yun, S. Y., Jang, J. M., Ha, H. C., Shin, I. C., Back, M. J., Piao, Y., & Kim, D. K. (2024) · Matrix Biology · doi:10.1016/j.matbio.2024.08.009 · Cited by 4
Recombinant GDF11 Promotes Recovery in a Rat Permanent Ischemia Model of Subacute Stroke
Cohen, O. S., Sinha, M., Wang, Y., Daman, T. H., Li, P., Deatherage, C. L., Charrez, B., Deshpande, A., Jordan, S., Makoni, N. J., et al. (2025) · Stroke · doi:10.1161/strokeaha.124.049908 · Cited by 4
“3,16 There were no differences in heart weight-to-tibial length ratios between rGDF11-treated aged mice and either vehicle-treated or rGDF11-treated young mice.”
Self-citationYu, A., Ma, C., & Hu, M. (2025) · Cells · doi:10.3390/cells14151153 · Cited by 4
“Heterochronic parabiosis has been reported to be able to rejuvenate some aging features of the old mice that were exposed to the young mice’s blood, and it was suggested that the hormone GDF11 (growth differentiation factor 11) mediated the rejuvenation effects [31,32].”
Stem Cell Senescence as the Memory of Past Injuries
Gianfranceschi, G., Gri, G., Cesselli, D., & Beltrami, A. P. (2015) · Current Pathobiology Reports · doi:10.1007/s40139-015-0071-5 · Cited by 4
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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