Redox Homeostasis in Age-Related Muscle Atrophy

Background: Muscle atrophy, i.e., the loss of skeletal muscle mass and function, is an unresolved problem associated with aging (sarcopenia) and several pathological conditions. The imbalance between myofibrillary protein breakdown (especially the adult isoforms of myosin heavy chain, MyHC) and synthesis, and the reduction of muscle regenerative potential are main causes of muscle atrophy. Methods: Starting from one-hundred dried hydroalcoholic extracts of medical plants, we identified those able to contrast the reduction of C2C12 myotube diameter in well-characterized in vitro models mimicking muscle atrophy associated to inflammatory states, glucocorticoid treatment or nutrient deprivation. Based on their ability to rescue type II MyHC (MyHC-II) expression in atrophying conditions, six extracts with different phytochemical profiles were selected, mixed in groups of three, and tested on atrophic myotubes. The molecular mechanism underpinning the effects of the most efficacious formulation, and its efficacy on myotubes obtained from muscle biopsies of young and sarcopenic subjects were also investigated. Results: We identified WST (Withania somnifera, Silybum marianum, Trigonella foenum-graecum) formulation as extremely efficacious in protecting C2C12 myotubes against MyHC-II degradation by stimulating Akt (protein kinase B)-dependent protein synthesis and p38 MAPK (p38 mitogen-activated protein kinase)/myogenin-dependent myoblast differentiation. WST sustains trophism in C2C12 and young myotubes, and rescues the size, developmental MyHC expression and myoblast fusion in sarcopenic myotubes. Conclusion: WST strongly counteracts muscle atrophy associated to different conditions in vitro. The future validation in vivo of our results might lead to the use of WST as a food supplement to sustain muscle mass in diffuse atrophying conditions, and to reverse the age-related functional decline of human muscles, thus improving people quality of life and reducing social and health-care costs.

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Random errors in protein synthesis activate an age-dependent program of muscle atrophy in mice

Communications Biology ◽

10.1038/s42003-021-02204-z ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

James Moore ◽

Rashid Akbergenov ◽

Martina Nigri ◽

Patricia Isnard-Petit ◽

Amandine Grimm ◽

...

Keyword(s):

Protein Synthesis ◽

Muscle Atrophy ◽

Strength Analysis ◽

Dependent Manner ◽

Random Errors ◽

Age Related ◽

Related Phenotype ◽

Age Dependent ◽

Translation Accuracy ◽

Transcriptomic Changes

AbstractRandom errors in protein synthesis are prevalent and ubiquitous, yet their effect on organismal health has remained enigmatic for over five decades. Here, we studied whether mice carrying the ribosomal ambiguity (ram) mutation Rps2-A226Y, recently shown to increase the inborn error rate of mammalian translation, if at all viable, present any specific, possibly aging-related, phenotype. We introduced Rps2-A226Y using a Cre/loxP strategy. Resulting transgenic mice were mosaic and showed a muscle-related phenotype with reduced grip strength. Analysis of gene expression in skeletal muscle using RNA-Seq revealed transcriptomic changes occurring in an age-dependent manner, involving an interplay of PGC1α, FOXO3, mTOR, and glucocorticoids as key signaling pathways, and finally resulting in activation of a muscle atrophy program. Our results highlight the relevance of translation accuracy, and show how disturbances thereof may contribute to age-related pathologies.

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NAD+Metabolism in Aging and Cancer

Annual Review of Cancer Biology ◽

10.1146/annurev-cancerbio-030518-055905 ◽

2019 ◽

Vol 3 (1) ◽

pp. 105-130 ◽

Cited By ~ 14

Author(s):

Tyler G. Demarest ◽

Mansi Babbar ◽

Mustafa N. Okur ◽

Xiuli Dan ◽

Deborah L. Croteau ◽

...

Keyword(s):

Molecular Mechanisms ◽

Therapeutic Potential ◽

Redox Homeostasis ◽

Accelerated Aging ◽

Cancer Therapies ◽

Nad Metabolism ◽

Cellular Processes ◽

Cancer Pathogenesis ◽

Nicotinamide Mononucleotide ◽

Age Related

Aging is a major risk factor for many types of cancer, and the molecular mechanisms implicated in aging, progeria syndromes, and cancer pathogenesis display considerable similarities. Maintaining redox homeostasis, efficient signal transduction, and mitochondrial metabolism is essential for genome integrity and for preventing progression to cellular senescence or tumorigenesis. NAD+is a central signaling molecule involved in these and other cellular processes implicated in age-related diseases and cancer. Growing evidence implicates NAD+decline as a major feature of accelerated aging progeria syndromes and normal aging. Administration of NAD+precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) offer promising therapeutic strategies to improve health, progeria comorbidities, and cancer therapies. This review summarizes insights from the study of aging and progeria syndromes and discusses the implications and therapeutic potential of the underlying molecular mechanisms involved in aging and how they may contribute to tumorigenesis.

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Randomized, four-arm, dose-response clinical trial to optimize resistance exercise training for older adults with age-related muscle atrophy

Experimental Gerontology ◽

10.1016/j.exger.2017.09.018 ◽

2017 ◽

Vol 99 ◽

pp. 98-109 ◽

Cited By ~ 27

Author(s):

Michael J. Stec ◽

Anna Thalacker-Mercer ◽

David L. Mayhew ◽

Neil A. Kelly ◽

S. Craig Tuggle ◽

...

Keyword(s):

Older Adults ◽

Clinical Trial ◽

Exercise Training ◽

Resistance Exercise ◽

Muscle Atrophy ◽

Dose Response ◽

Resistance Exercise Training ◽

Age Related

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Potential for treatment of age‐related muscle atrophy by exogenous nitric oxide and exercise

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.175.5 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Jeff R.S. Leiter ◽

Alyssa Janke ◽

Melody Ong ◽

Stephane Lenoski ◽

Ritika Upadhaya ◽

...

Keyword(s):

Nitric Oxide ◽

Muscle Atrophy ◽

Age Related ◽

Exogenous Nitric Oxide

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Dkk3 dependent transcriptional regulation controls age related skeletal muscle atrophy

Nature Communications ◽

10.1038/s41467-018-04038-6 ◽

2018 ◽

Vol 9 (1) ◽

Cited By ~ 10

Author(s):

Jie Yin ◽

Lele Yang ◽

Yangli Xie ◽

Yan Liu ◽

Sheng Li ◽

...

Keyword(s):

Skeletal Muscle ◽

Transcriptional Regulation ◽

Muscle Atrophy ◽

Skeletal Muscle Atrophy ◽

Age Related

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Neuroprotective Potential of Ginkgo biloba in Retinal Diseases

Planta Medica ◽

10.1055/a-0947-5712 ◽

2019 ◽

Vol 85 (17) ◽

pp. 1292-1303 ◽

Cited By ~ 9

Author(s):

Isabel Martínez-Solís ◽

Nuria Acero ◽

Francisco Bosch-Morell ◽

Encarna Castillo ◽

María Eugenia González-Rosende ◽

...

Keyword(s):

Oxidative Stress ◽

Ginkgo Biloba ◽

Redox Homeostasis ◽

Antioxidant Properties ◽

Retinal Disease ◽

Age Related Macular Degeneration ◽

Retinal Diseases ◽

Age Related ◽

The Central Nervous System ◽

Degenerative Processes

AbstractLike other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this, Ginkgo biloba is a medicinal plant with excellent antioxidant properties whose effects have been demonstrated in several degenerative processes, including retinal diseases associated with neurodegeneration. This review describes the current literature on the role of ginkgo in retinal diseases associated with neurodegeneration. The information leads to the conclusion that G. biloba extracts might be a good option to improve certain neurodegenerative retinal diseases, but more research is needed to determine the safety and efficacy of G. biloba in these retinal degenerative processes.

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Reversal of age-associated oxidative stress in mice by PFT, a novel kefir product

International Journal of Immunopathology and Pharmacology ◽

10.1177/2058738420950149 ◽

2020 ◽

Vol 34 ◽

pp. 205873842095014

Author(s):

Mamdooh Ghoneum ◽

Shaymaa Abdulmalek ◽

Deyu Pan

Keyword(s):

Oxidative Stress ◽

Low Density Lipoprotein ◽

Redox Homeostasis ◽

Density Lipoprotein ◽

Antioxidant Enzyme Activities ◽

Protective Effects ◽

Oxidative Stress Biomarkers ◽

Age Related ◽

Total Antioxidant ◽

The Brain

Introduction: Oxidative stress is a key contributor to aging and age-related diseases. In the present study, we examine the protective effects of PFT, a novel kefir product, against age-associated oxidative stress using aged (10-month-old) mice. Methods: Mice were treated with PFT orally at a daily dose of 2 mg/kg body weight over 6 weeks, and antioxidant status, protein oxidation, and lipid peroxidation were studied in the brain, liver, and blood. Results: PFT supplementation significantly reduced the oxidative stress biomarkers malondialdehyde (MDA) and nitric oxide; reversed the reductions in glutathione (GSH) levels, total antioxidant capacity (TAC), and anti-hydroxyl radical (AHR) content; enhanced the antioxidant enzyme activities of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD); inhibited the liver enzyme levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT); significantly reduced triglyceride (TG), total cholesterol (TC), and low density lipoprotein (LDL) levels; and significantly elevated high density lipoprotein (HDL) levels. Interestingly, PFT supplementation reversed the oxidative changes associated with aging, thus bringing levels to within the limits of the young control mice in the brain, liver, and blood. We also note that PFT affects the redox homeostasis of young mice and that it is corrected post-treatment with PFT. Conclusion: Our findings show the effectiveness of dietary PFT supplementation in modulating age-associated oxidative stress in mice and motivate further studies of PFT’s effects in reducing age-associated disorders where free radicals and oxidative stress are the major cause.

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