An ingredient for the elixir of youth

Andersen, Rebecca; Lim, Daniel

doi:10.1038/cr.2014.107

Cited by 20 publications

(12 citation statements)

References 10 publications

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“…Initial studies [12, 27] showed that GDF11 declines with age, and that the reintroduction of this “elixir of youth” [1] reverses age-related degenerative changes in the body, including cardiac hypertrophy and skeletal muscle dysfunction/atrophy [12, 20, 27]. However in vivo studies by Smith et al reported no changes in cardiac structure or function with GDF11 administration [28].…”

Section: Discussionmentioning

confidence: 99%

“…GDF11 was first described as a secreted factor involved in tooth development [17], axial patterning, and kidney organogenesis [15]. More recently, work in adult mice reports regenerative activities for GDF11, with some describing it as the “elixir of youth” because it appeared to decline with age, and exogenous dosing reversed cardiac hypertrophy and improved skeletal muscle in aged animals [1, 12, 27]. Subsequent research questioned these initial conclusions, with disagreements arising regarding the quality and accuracy of the reagents and assays used in the experimental procedures as well as in the interpretation of the results [6, 20, 24].…”

Section: Introductionmentioning

confidence: 99%

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Exogenous GDF11 induces cardiac and skeletal muscle dysfunction and wasting

et al. 2017

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SUMMARY Growth differentiation factor 11 (GDF11), a TGF-beta super-family 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. GDF11 exposure in mice induced whole body wasting and profound loss of function in cardiac and skeletal muscle over a 14-day period. Loss of cardiac mass preceded skeletal muscle loss. Cardiac histologic and echocardiographic evaluation demonstrated loss of ventricular muscle wall thickness, decreased cardiomyocyte size and decreased cardiac function 10 days following initiation of GDF11 exposure. Changes in skeletal muscle after GDF11 exposure were manifest at day 13 and associated with wasting, decreased fiber size, and reduced strength. Changes in cardiomyocytes and skeletal muscle fibers were associated with activation of SMAD2, the ubiquitin-proteasome pathway and autophagy. GDF11 over administration in vivo results in cardiac and skeletal muscle loss, dysfunction and death. Serum levels of GDF11 by Western blotting were 1.5 fold increased over controls. Although GDF11 effects in vivo are likely dose, route, and duration dependent, its physiologic changes are similar to myostatin and other Activin receptors ligands. These data support that GDF11, like its other closely related TGF-beta family members, induces loss of cardiac and skeletal muscle mass and function.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exogenous GDF11 induces cardiac and skeletal muscle dysfunction and wasting

et al. 2017

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“…[137][138][139] ActRIIA and ActRIIB are recognized by several ligands, including GDF11, and have been involved in a variety of physiological functions, including bone homeostasis and age-related bone loss. 140 The trap ligand ACE-011 was made by fusing the extracellular domain of ActRIIA to the Fc domain of human IgG1.…”

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confidence: 99%

-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies

2015

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b-thalassemias are monogenic disorders characterized by defective synthesis of the b-globin chain, one of the major components of adult hemoglobin. A large number of mutations in the b-globin gene or its regulatory elements have been associated with b-thalassemias. Due to the complexity of the regulation of the b-globin gene and the role of red cells in many physiological processes, patients can manifest a large spectrum of phenotypes, and clinical requirements vary from patient to patient. It is important to consider the major differences in the light of potential novel therapeutics. This review summarizes the main discoveries and mechanisms associated with the synthesis of b-globin and abnormal erythropoiesis, as well as current and novel therapies. ABSTRACTThe complex phenotype of b-thalassemias b-thalassemias are monogenic disorders characterized by reduced or no synthesis of the b-globin chain, one of the major components of adult hemoglobin (HbA). Several hundred mutations in the b-globin gene or regulatory elements have been associated with b-thalassemias.

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“…This explores the complex relationships between the parts of a dynamic system in relation to the whole, and the interdependency of such structures of dynamic systems [6] . Despite a large number of reports that a drug, nutrient, procedure, compound or other, prolongs healthy lifespan in laboratory animals, human beneficial mirroring effects have yet to be realized [7][8][9][10][11][12][13][14][15][16][17] . In part, this is due to the reductionist method employed by the vast majority of researchers which does not take into account the unique characteristics of humans.…”

Section: Introductionmentioning

confidence: 99%

The failure of “engineered rejuvenation”: laboratory genomics do not translate into precision anti-aging therapies

Kyriazis¹

2018

JTGG

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There is a general failure of reductionist and mechanistic approaches to rejuvenation biomedical technologies which aim at providing treatments against aging (defined as "time-dependent dysfunction"). Importantly, it is becoming increasingly recognised that genomic research findings in animals may not adequately be translated into effective human anti-aging therapies. There exist translational impediments, which although individually formidable, can theoretically be overcome. However, the combined effects of these obstacles render this reductionist avenue of quest unattainable, at least for the foreseeable future. Some of the clinical problems of physical and genomic-based therapies against aging include side effects, interactions, inter-subject variability, compliance, patient self-reporting of data, motivation, administrative issues, infrastructure, etc. A systematic review spanning over the past 5 years, describes these problems and identifies novel approaches. New and emerging disciplines and concepts such as molecular pathological epidemiology, social genomics and other "systems-thinking" methods provide a more comprehensive view of the entire subject of aging, and study its indivisible bonds with the environment, society and culture. The so-called "fountain of youth" cannot be found in a physical item.

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An ingredient for the elixir of youth

Cited by 20 publications

References 10 publications

Exogenous GDF11 induces cardiac and skeletal muscle dysfunction and wasting

Exogenous GDF11 induces cardiac and skeletal muscle dysfunction and wasting

-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies

The failure of “engineered rejuvenation”: laboratory genomics do not translate into precision anti-aging therapies

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