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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
Lucia Maria Leitner, Rebecca June Wilson, Zhen Yan, Axel Gödecke
SIGNIFICANCE: Cachexia is defined as a complex metabolic syndrome associated with underlying illness and a loss of muscle with or without loss of fat mass. This disease is associated with high incidence with chronic diseases such as heart failure, cancer, chronic obstructive pulmonary disease, AIDS, among others. Since there is currently no effective treatment available, cachectic patients have a poor prognosis. Elucidation of the underlying mechanisms is therefore an important medical task...
November 11, 2016: Antioxidants & Redox Signaling
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
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. Utilizing 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, a reduced lean muscle mass, and increased adipose tissue...
September 9, 2016: Endocrinology
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
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
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...
August 10, 2016: Vox Sanguinis
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 5, 2016: Oncotarget
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...
October 11, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
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
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
Yusi Chen, Qi Guo, Min Zhang, Shumin Song, Tonggui Quan, Tiepeng Zhao, Hongliang Li, Lijuan Guo, Tiejian Jiang, Guangwei Wang
Growth differentiation factor 11 (GDF11) is an important circulating factor that regulates aging. However, the role of GDF11 in bone metabolism remains unclear. The present study was undertaken to investigate the relationship between serum GDF11 level, bone mass, and bone turnover markers in postmenopausal Chinese women. Serum GDF11 level, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 169 postmenopausal Chinese women (47-78 years old). GDF11 serum levels increased with aging...
2016: Bone Research
Qiong Lu, Man-Li Tu, Chang-Jun Li, Li Zhang, Tie-Jian Jiang, Tang Liu, Xiang-Hang Luo
Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β superfamily. Recent studies confirmed that GDF11 plays an important role in regulating the regeneration of brain, skeletal muscle, and heart during aging; however, its role in bone metabolism remains unclear. Thus, the aim of this study was to determine the effects of GDF11 on bone metabolism, including bone formation and bone resorption, both in vitro and in vivo. Our results showed that GDF11 inhibited osteoblastic differentiation of bone marrow mesenchymal stem cells in vitro...
July 9, 2016: Calcified Tissue International
Ashraf M Khalil, Hyna Dotimas, Julius Kahn, Jane E Lamerdin, David B Hayes, Priyanka Gupta, Michael Franti
Growth differentiation factor-11 (GDF11) and myostatin (MSTN) are highly related transforming growth factor-β (TGF-β) ligands with 89% amino acid sequence homology. They have different biologic activities and diverse tissue distribution patterns. However, the activities of these ligands are indistinguishable in in vitro assays. SMAD2/3 signaling has been identified as the canonical pathway for GDF11 and MSTN, However, it remains unclear which receptor heterodimer and which antagonists preferentially mediate and regulate signaling...
September 2016: Journal of Pharmacology and Experimental Therapeutics
Olivier Monestier, Véronique Blanquet
The WFIKKN (WAP, Follistatin/kazal, Immunoglobulin, Kunitz and Netrin domain-containing) protein family is composed of two multidomain proteins: WFIKKN1 and WFIKKN2. They were formed by domain shuffling and are likely present in deuterostoms. The WFIKKN (also called GASP) proteins are well known for their function in muscle and skeletal tissues, namely, inhibition of certain members of the transforming growth factor beta (TGFB) superfamily such as myostatin (MSTN) and growth and differentiation factor 11 (GDF11)...
December 2016: Cytokine & Growth Factor Reviews
Long-Chao Zhang, Jing-Wei Yue, Lei Pu, Li-Gang Wang, Xin Liu, Jing Liang, Hua Yan, Ke-Bin Zhao, Na Li, Hui-Bi Shi, Yue-Bo Zhang, Li-Xian Wang
In China, sparerib is one of the most valuable parts of the pork carcass. As a result, candidate gene mining for number of ribs has become an interesting study focus. To examine the genetic basis for this major trait, we genotyped 596 individuals from an F2 Large White × Minzhu intercross pig population using the PorcineSNP60 Genotyping BeadChip. The genome-wide association study identified a locus for number of ribs in a 2.38-Mb region on Sus scrofa chromosome 7 (SSC7 of Sus scrofa genome assembly, Sscrofa10...
October 2016: Molecular Genetics and Genomics: MGG
Marissa J Schafer, Elizabeth J Atkinson, Patrick M Vanderboom, Brian Kotajarvi, Thomas A White, Matthew M Moore, Charles J Bruce, Kevin L Greason, Rakesh M Suri, Sundeep Khosla, Jordan D Miller, H Robert Bergen, Nathan K LeBrasseur
Growth and differentiation factor 11 (GDF11) is a transforming growth factor β superfamily member with a controversial role in aging processes. We have developed a highly specific LC-MS/MS assay to quantify GDF11, resolved from its homolog, myostatin (MSTN), based on unique amino acid sequence features. Here, we demonstrate that MSTN, but not GDF11, declines in healthy men throughout aging. Neither GDF11 nor MSTN levels differ as a function of age in healthy women. In an independent cohort of older adults with severe aortic stenosis, we show that individuals with higher GDF11 were more likely to be frail and have diabetes or prior cardiac conditions...
June 14, 2016: Cell Metabolism
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...
2016: Skeletal Muscle
Sho-Ichi Yamagishi, Takanori Matsui, Yuka Kurokawa, Kei Fukami
Circulating levels of growth differentiation factor 11 (GDF11) have been shown to decrease with age in several mammalian species, and supplementation of GDF11 by heterochronic parabiosis or systemic administration reverses age-related organ damage. However, there is some controversy about the pathophysiological role of GDF11 in aging-associated organ damage. Since aging process is accelerated in uremia, we compared serum levels of GDF11 in hemodialysis (HD) patients with those in age-matched healthy controls, and then determined the independent clinical correlates of GDF11 in HD subjects...
2016: BioResearch Open Access
Buel D Rodgers
No abstract text is available yet for this article.
May 13, 2016: Circulation Research
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