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GDF11 and aging

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
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
Kay-Marie Lamar, Sasha Bogdanovich, Brandon B Gardner, Quan Q Gao, Tamari Miller, Judy U Earley, Michele Hadhazy, Andy H Vo, Lisa Wren, Jeffery D Molkentin, Elizabeth M McNally
Latent TGFβ binding proteins (LTBPs) regulate the extracellular availability of latent TGFβ. LTBP4 was identified as a genetic modifier of muscular dystrophy in mice and humans. An in-frame insertion polymorphism in the murine Ltbp4 gene associates with partial protection against muscular dystrophy. In humans, nonsynonymous single nucleotide polymorphisms in LTBP4 associate with prolonged ambulation in Duchenne muscular dystrophy. To better understand LTBP4 and its role in modifying muscular dystrophy, we created transgenic mice overexpressing the protective murine allele of LTBP4 specifically in mature myofibers using the human skeletal actin promoter...
May 2016: PLoS Genetics
Aaron C Hinken, Janine M Powers, Guizhen Luo, Jason A Holt, Andrew N Billin, Alan J Russell
Recent high-profile studies report GDF11 to be a key circulating 'anti-aging' factor. However, a screen of extracellular proteins attempting to identify factors with 'anti-aging' phenotypes in aged murine skeletal muscle satellite cells did not identify GDF11 activity. We have been unable to confirm the reported activity of GDF11, similar to other laboratories offering conflicting data and describe our attempts to do so in this short take.
June 2016: Aging Cell
Shavonn C Harper, Andrew Brack, Scott MacDonnell, Michael Franti, Bradley B Olwin, Beth A Bailey, Michael A Rudnicki, Steven R Houser
This "Controversies in Cardiovascular Research" article evaluates the evidence for and against the hypothesis that the circulating blood level of growth differentiation factor 11 (GDF11) decreases in old age and that restoring normal GDF11 levels in old animals rejuvenates their skeletal muscle and reverses pathological cardiac hypertrophy and cardiac dysfunction. Studies supporting the original GDF11 hypothesis in skeletal and cardiac muscle have not been validated by several independent groups. These new studies have either found no effects of restoring normal GDF11 levels on cardiac structure and function or have shown that increasing GDF11 or its closely related family member growth differentiation factor 8 actually impairs skeletal muscle repair in old animals...
April 1, 2016: Circulation Research
Ryan G Walker, Tommaso Poggioli, Lida Katsimpardi, Sean M Buchanan, Juhyun Oh, Sam Wattrus, Bettina Heidecker, Yick W Fong, Lee L Rubin, Peter Ganz, Thomas B Thompson, Amy J Wagers, Richard T Lee
Growth differentiation factor 11 (GDF11) and myostatin (or GDF8) are closely related members of the transforming growth factor β superfamily and are often perceived to serve similar or overlapping roles. Yet, despite commonalities in protein sequence, receptor utilization and signaling, accumulating evidence suggests that these 2 ligands can have distinct functions in many situations. GDF11 is essential for mammalian development and has been suggested to regulate aging of multiple tissues, whereas myostatin is a well-described negative regulator of postnatal skeletal and cardiac muscle mass and modulates metabolic processes...
April 1, 2016: Circulation Research
Yong-Hui Zhang, Feng Cheng, Xue-Ting Du, Jin-Lai Gao, Xiao-Lin Xiao, Na Li, Shan-Liang Li, De Li Dong
GDF11/BMP11, a member of TGF-β superfamily, was reported to rejuvenate heart, skeletal muscle and blood vessel architecture in aged mice. However, the rejuvenative effects of GDF11 were questioned recently. Here, we investigated the effects of GDF11 on smad and non-smad signals in human umbilical vein endothelial cells (HUVECs) and the effects of GDF11 on proliferation and migration of HUVECs and primary rat aortic endothelial cells (RAECs). GDF11 factor purchased from two different companies (PeproTech and R&D Systems) was comparatively studied...
March 15, 2016: Oncotarget
Elizabeth M McNally
No abstract text is available yet for this article.
January 8, 2016: Circulation Research
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