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GDF11 and aging

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https://www.readbyqxmd.com/read/28647906/exogenous-gdf11-induces-cardiac-and-skeletal-muscle-dysfunction-and-wasting
#1
Teresa A Zimmers, Yanling Jiang, Meijing Wang, Tiffany W Liang, Joseph E Rupert, Ernie D Au, Francesco E Marino, Marion E Couch, Leonidas G Koniaris
Growth differentiation factor 11 (GDF11), a TGF-beta superfamily member, is highly homologous to myostatin and essential for embryonic patterning and organogenesis. Reports of GDF11 effects on adult tissues are conflicting, with some describing anti-aging and pro-regenerative activities on the heart and skeletal muscle while others opposite or no effects. Herein, we sought to determine the in vivo cardiac and skeletal muscle effects of excess GDF11. Mice were injected with GDF11 secreting cells, an identical model to that used to initially identify the in vivo effects of myostatin...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28508553/a-targeted-proteomic-assay-for-the-measurement-of-plasma-proteoforms-related-to-human-aging-phenotypes
#2
Richard D Semba, Pingbo Zhang, Min Zhu, Elisa Fabbri, Marta Gonzalez-Freire, Ruin Moaddel, Minghui Geng-Spyropoulos, Luigi Ferrucci
Circulating polypeptides and proteins have been implicated in reversing or accelerating aging phenotypes, including growth/differentiation factor 8 (GDF8), GDF11, eotaxin, and oxytocin. These proteoforms, which are defined as the protein products arising from a single gene due to alternative splicing and post-translational modifications, have been challenging to study. Both GDF8 and GDF11 have known antagonists such as follistatin (FST), and WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing proteins 1 and 2 (WFIKKN1, WFIKKN2)...
May 16, 2017: Proteomics
https://www.readbyqxmd.com/read/28485800/gdf11-does-not-improve-the-palmitate-induced-insulin-resistance-in-c2c12
#3
Y-Y Jing, D Li, F Wu, L-L Gong, R Li
OBJECTIVE: GDF11 (Growth Differentiation factor 11) has been reported to rejuvenate skeletal muscle, heart and brain in aged mice, and the aged skeletal muscle is closely related to insulin resistance. We wondered whether GDF11 has an effect on skeletal muscle insulin resistance. MATERIALS AND METHODS: High fat diet induced obese mice with insulin resistance were established in vivo. Palmitate-induced insulin resistance in C2C12 myotubes was established in vitro...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28472635/the-growth-differentiation-factor-11-gdf11-and-myostatin-mstn-in-tissue-specific-aging
#4
REVIEW
Xiaolan Fan, Uma Gaur, Lin Sun, Deying Yang, Mingyao Yang
Growth differentiation factor 11 (GDF11) and myostatin (MSTN) are evolutionarily conserved homologues proteins which are closely related members of the transforming growth factor β superfamily. They are often perceived to serve similar or overlapping roles. Recently, GDF11 has been identified as playing a role during aging, however there are conflicting reports as to the nature of this role. In this review, we will discuss the literature regarding functions of GDF11 and myostatin in the heart, brain, and skeletal muscle during aging...
May 1, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28455454/decrease-in-an-anti-ageing-factor-growth-differentiation-factor-11-in-chronic-obstructive-pulmonary-disease
#5
Katsuhiro Onodera, Hisatoshi Sugiura, Mitsuhiro Yamada, Akira Koarai, Naoya Fujino, Satoru Yanagisawa, Rie Tanaka, Tadahisa Numakura, Shinsaku Togo, Kei Sato, Yorihiko Kyogoku, Yuichiro Hashimoto, Tatsuma Okazaki, Tsutomu Tamada, Seiichi Kobayashi, Masaru Yanai, Motohiko Miura, Yasushi Hoshikawa, Yoshinori Okada, Satoshi Suzuki, Masakazu Ichinose
RATIONALE: Cellular senescence is observed in the lungs of patients with COPD and may contribute to the disease pathogenesis. Growth differentiation factor 11 (GDF11) belongs to the transforming growth factor β superfamily and was recently reported to be a circulating protein that may have rejuvenating effects in mice. We aimed to investigate the amounts of GDF11 in the plasma and the lungs of patients with COPD and elucidate the possible roles of GDF11 in cellular senescence. METHODS: The plasma levels of GDF11 were investigated in two separate cohorts by western blotting...
April 28, 2017: Thorax
https://www.readbyqxmd.com/read/28450417/gdf11-attenuates-development-of-type-2-diabetes-via-improvement-of-islet-%C3%AE-cell-function-and-survival
#6
Huan Li, Yixiang Li, Lingwei Xiang, JiaJia Zhang, Biao Zhu, Lin Xiang, Jing Dong, Min Liu, Guangda Xiang
Growth differentiation factor 11 (GDF11) has been implicated in the regulation of islet development and a variety of aging conditions, but little is known about the physiological functions of GDF11 in adult pancreatic islets. Here, we showed that systematic replenishment of GDF11 not only preserved insulin secretion but also improved the survival and morphology of β cells as well as improved glucose metabolism in both non-genetic and genetic mouse models of type 2 diabetes (T2D). Conversely, anti-GDF11 monoclonal antibody treatment caused β cell failure and lethal T2D...
April 27, 2017: Diabetes
https://www.readbyqxmd.com/read/28270449/supraphysiological-levels-of-gdf11-induce-striated-muscle-atrophy
#7
David W Hammers, Melissa Merscham-Banda, Jennifer Ying Hsiao, Stefan Engst, James J Hartman, H Lee Sweeney
Growth and differentiation factor (GDF) 11 is a member of the transforming growth factor β superfamily recently identified as a potential therapeutic for age-related cardiac and skeletal muscle decrements, despite high homology to myostatin (Mstn), a potent negative regulator of muscle mass. Though several reports have refuted these data, the in vivo effects of GDF11 on skeletal muscle mass have not been addressed. Using in vitro myoblast culture assays, we first demonstrate that GDF11 and Mstn have similar activities/potencies on activating p-SMAD2/3 and induce comparable levels of differentiated myotube atrophy...
April 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28257634/structural-basis-for-potency-differences-between-gdf8-and-gdf11
#8
Ryan G Walker, Magdalena Czepnik, Erich J Goebel, Jason C McCoy, Ana Vujic, Miook Cho, Juhyun Oh, Senem Aykul, Kelly L Walton, Gauthier Schang, Daniel J Bernard, Andrew P Hinck, Craig A Harrison, Erik Martinez-Hackert, Amy J Wagers, Richard T Lee, Thomas B Thompson
BACKGROUND: Growth/differentiation factor 8 (GDF8) and GDF11 are two highly similar members of the transforming growth factor β (TGFβ) family. While GDF8 has been recognized as a negative regulator of muscle growth and differentiation, there are conflicting studies on the function of GDF11 and whether GDF11 has beneficial effects on age-related dysfunction. To address whether GDF8 and GDF11 are functionally identical, we compared their signaling and structural properties. RESULTS: Here we show that, despite their high similarity, GDF11 is a more potent activator of SMAD2/3 and signals more effectively through the type I activin-like receptor kinase receptors ALK4/5/7 than GDF8...
March 3, 2017: BMC Biology
https://www.readbyqxmd.com/read/28004242/targeted-myocardial-delivery-of-gdf11-gene-rejuvenates-the-aged-mouse-heart-and-enhances-myocardial-regeneration-after-ischemia-reperfusion-injury
#9
Guo-Qing Du, Zheng-Bo Shao, Jie Wu, Wen-Juan Yin, Shu-Hong Li, Jun Wu, Richard D Weisel, Jia-Wei Tian, Ren-Ke Li
Ischemic cardiac injury is the main contributor to heart failure, and the regenerative capacity of intrinsic stem cells plays an important role in tissue repair after injury. However, stem cells in aged individuals have reduced regenerative potential and aged tissues lack the capacity to renew. Growth differentiation factor 11 (GDF11), from the activin-transforming growth factor β superfamily, has been shown to promote stem cell activity and rejuvenation. We carried out non-invasive targeted delivery of the GDF11 gene to the heart using ultrasound-targeted microbubble destruction (UTMD) and cationic microbubble (CMB) to investigate the ability of GDF11 to rejuvenate the aged heart and improve tissue regeneration after injury...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27924614/gdf11-treatment-attenuates-the-recovery-of-skeletal-muscle-function-after-injury-in-older-rats
#10
Yu Zhou, Neel Sharma, David Dukes, Maria B Myzithras, Priyanka Gupta, Ashraf Khalil, Julius Kahn, Jennifer S Ahlberg, David B Hayes, Michael Franti, Tracy Criswell
Loss of skeletal muscle mass and function results in loss of mobility for elderly patients. Novel therapies that can protect and/or restore muscle function during aging would have profound effects on the quality of life for this population. Growth differentiation factor 11 (GDF11) has been proposed as a "youthful" circulating factor that can restore cardiac, neural, and skeletal muscle functions in aging animals. However, conflicting data has been recently published that casts doubt on these assertions. We used a complex rat model of skeletal muscle injury that physiologically mimics injuries seen in patients; to investigate the ability of GDF11 and to enhance skeletal muscle regeneration after injury in older rats...
March 2017: AAPS Journal
https://www.readbyqxmd.com/read/27906064/treatment-with-rgdf11-does-not-improve-the-dystrophic-muscle-pathology-of-mdx-mice
#11
Fabrizio Rinaldi, Yu Zhang, Ricardo Mondragon-Gonzalez, Jeffrey Harvey, Rita C R Perlingeiro
BACKGROUND: Duchenne muscular dystrophy (DMD) is an inherited lethal muscle wasting disease characterized by cycles of degeneration and regeneration, with no effective therapy. Growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily and myostatin homologous, has been reported to have the capacity to reverse age-related skeletal muscle loss. These initial findings led us to investigate the ability of GDF11 to promote regeneration in the context of muscular dystrophy and determine whether it could be a candidate to slow down or reverse the disease progression in DMD...
June 14, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27703192/gdf11-improves-tubular-regeneration-after-acute-kidney-injury-in-elderly-mice
#12
Ying Zhang, Qinggang Li, Dong Liu, Qi Huang, Guangyan Cai, Shaoyuan Cui, Xuefeng Sun, Xiangmei Chen
The GDF11 expression pattern and its effect on organ regeneration after acute injury in the elderly population are highly controversial topics. In our study, GDF11/8 expression increased after kidney ischemia-reperfusion injury (IRI), and the relatively lower level of GDF11/8 in the kidneys of aged mice was associated with a loss of proliferative capacity and a decline in renal repair, compared to young mice. In vivo, GDF11 supplementation in aged mice increased vimentin and Pax2 expression in the kidneys as well as the percentage of 5-ethynyl-2'-deoxyuridine (EdU)-positive proximal tubular epithelial cells...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27611336/tgf%C3%AE-superfamily-members-mediate-androgen-deprivation-therapy-induced-obese-frailty-in-male-mice
#13
Chunliu Pan, Shalini Singh, Deepak M Sahasrabudhe, Joe V Chakkalakal, John J Krolewski, Kent L Nastiuk
First line treatment for recurrent and metastatic prostate cancer is androgen deprivation therapy (ADT). Use of ADT has been increasing in frequency and duration, such that side effects increasingly impact patient quality of life. One of the most significant side effects of ADT is sarcopenia, which leads to a loss of skeletal muscle mass and function, resulting in a clinical disability syndrome known as obese frailty. Using aged mice, we developed a mouse model of ADT-induced sarcopenia that closely resembles the phenotype seen in patients, including loss of skeletal muscle strength, reduced lean muscle mass, and increased adipose tissue...
November 2016: Endocrinology
https://www.readbyqxmd.com/read/27565745/does-growth-differentiation-factor-11-protect-against-myocardial-ischaemia-reperfusion-injury-a-hypothesis
#14
Yongjian Yang, Yi Yang, Xiong Wang, Jin Du, Juanni Hou, Juan Feng, Yue Tian, Lei He, Xiuchuan Li, Haifeng Pei
The pathogenesis of myocardial ischaemia/reperfusion injury is multifactorial. Understanding the mechanisms of myocardial ischaemia/reperfusion will benefit patients with ischaemic heart disease. Growth differentiation factor 11 (GDF11), a member of the secreted transforming growth factor-β superfamily, has been found to reverse age-related hypertrophy, revealing the important role of GDF11 in cardiovascular disease. However, the functions of GDF11 in myocardial ischaemia/reperfusion have not been elucidated yet...
August 25, 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27557752/increased-serum-gdf11-concentration-is-associated-with-a-high-prevalence-of-osteoporosis-in-elderly-native-chinese-women
#15
Miaomiao Jin, Shumin Song, Lijuan Guo, Tiejian Jiang, Zhangyuan Lin
Osteoporosis is an age-related disease. Many studies have confirmed the anti-aging effect of growth differentiation factor 11 (GDF11), but the action of GDF11 on bone metabolism remains unclear. In this study, we aimed to investigate the relationship between serum GDF11 levels and the prevalence of osteoporosis. Our data indicated negative correlations between serum GDF11 levels and BMD at the lumbar spine and femoral neck. The serum GDF11 levels were grouped into quartile intervals, and the prevalence and risk of osteoporosis were found be markedly greater with increased GDF11 levels...
August 25, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27509407/growth-differentiation-factor-11-gdf11-a-promising-anti-ageing-factor-is-highly-concentrated-in-platelets
#16
J L Bueno, M Ynigo, C de Miguel, R M Gonzalo-Daganzo, A Richart, C Vilches, C Regidor, J A García-Marco, E Flores-Ballester, J R Cabrera
Recent research suggests that growth differentiation factor 11 (GDF11) could reverse age-related diseases and that its blood concentration decreases with age. This poses plasma from young donors as a therapeutic GDF11 source to treat age-related diseases. In addition, the tissue source of circulating GDF11 remains unknown. We analysed GDF11 levels in paired samples of serum, plasma and platelet lysate (PL) from 23 volunteers. Plasma and PL were collected by plateletpheresis. Here, we show that GDF11 is highly concentrated in platelets and that the circulating levels reported in previous studies could be biased as a result of serum sample manipulation...
November 2016: Vox Sanguinis
https://www.readbyqxmd.com/read/27507054/gdf11-administration-does-not-extend-lifespan-in-a-mouse-model-of-premature-aging
#17
Sandra Freitas-Rodríguez, Francisco Rodríguez, Alicia R Folgueras
GDF11 has recently emerged as a powerful anti-aging candidate, found in young blood, capable of rejuvenating a number of aged tissues, such as heart, skeletal muscle and brain. However, recent reports have shown contradictory data questioning its capacity to reverse age-related tissue dysfunction. The availability of a mouse model of accelerated aging, which shares most of the features occurring in physiological aging, gives us an excellent opportunity to test in vivo therapies aimed at extending lifespan both in pathological and normal aging...
August 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27502608/gdf11-protects-against-endothelial-injury-and-reduces-atherosclerotic-lesion-formation-in-apolipoprotein-e-null-mice
#18
Wen Mei, Guangda Xiang, Yixiang Li, Huan Li, Lingwei Xiang, Junyan Lu, Lin Xiang, Jing Dong, Min Liu
Growth differentiation factor 11 (GDF11) reduces cardiac hypertrophy, improves cerebral vasculature and enhances neurogenesis in ageing mice. Higher growth differentiation factor 11/8 (GDF11/8) is associated with lower risk of cardiovascular events in humans. Here, we showed that adeno-associated viruses-GDF11 and recombinant GDF11 protein improve endothelial dysfunction, decrease endothelial apoptosis, and reduce inflammation, consequently decrease atherosclerotic plaques area in apolipoprotein E(-/-) mice...
November 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/27426744/-pro-youthful-factors-in-the-labyrinth-of-cardiac-rejuvenation
#19
REVIEW
Luc Rochette, Catherine Vergely
The mechanisms of aging and senescence include various endogenous and exogenous factors. Among cardiovascular diseases, heart failure is a typical age-related disease. New strategies to restore cardiomyocyte cells have been reported: endogenous substances that can regenerate the heart's cardiomyocytes have been described: follistatin like 1 (FSTL1), growth-differentiation factor 11 (GDF11) and insulin-like growth factor 1 (IGF-I). Manipulation of the different anti and pro- pathways is essential to discover new approaches to regenerative therapies...
October 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27411004/elevated-gdf11-is-a-risk-factor-for-age-related-frailty-and-disease-in-humans
#20
David J Glass
GDF11 was reported to decline with age and to have muscle and heart rejuvenating effects. These reports were disputed. A Cell Metabolism paper now shows that in human beings, GDF11 does not decline with age and is actually a risk factor for frailty and other morbidities (Schafer et al., 2016).
July 12, 2016: Cell Metabolism
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