Article
Geriatrics & Gerontology
Trace Thome, Kayla Miguez, Alexander Willms, Sarah K. Burke, Vijayendran Chandran, Angela R. de Souza, Liam F. Fitzgerald, Carolyn Baglole, Maria-Eleni Anagnostou, Jean Bourbeau, R. Thomas Jagoe, Jose A. Morais, Yana Goddard, Tanja Taivassalo, Terence E. Ryan, Russell T. Hepple
Summary: Chronic activation of the aryl hydrocarbon receptor (AHR) induced by tobacco smoke exposure mimics muscle atrophy, mitochondrial impairment, and neuromuscular junction degeneration. Studies show that smoke exposure causes down-regulation of mitochondrial and neuromuscular junction genes, as well as activation of muscle AHR signaling.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2021)
Article
Cell Biology
Madoka Ikemoto-Uezumi, Heying Zhou, Tamaki Kurosawa, Yuki Yoshimoto, Masashi Toyoda, Nobuo Kanazawa, Tatsu Nakazawa, Mitsuhiro Morita, Kunihiro Tsuchida, Akiyoshi Uezumi
Summary: The study reveals an association between increased MFG-E8 levels in skeletal muscle and sarcopenia, suggesting that MFG-E8 may contribute to the degeneration of neuromuscular junctions. Targeting MFG-E8 could be a promising therapeutic approach to prevent sarcopenia.
Article
Biochemistry & Molecular Biology
Anna S. Nichenko, Jacob R. Sorensen, W. Michael Southern, Anita E. Qualls, Albino G. Schifino, Jennifer McFaline-Figueroa, Jamie E. Blum, Kayvan F. Tehrani, Hang Yin, Luke J. Mortensen, Anna E. Thalacker-Mercer, Sarah M. Greising, Jarrod A. Call
Summary: This study investigated the role of Ulk1-mediated autophagy in skeletal muscle aging by using muscle-specific Ulk1 knockout mice. Findings suggest that under Ulk1 deficiency, muscle contractile and metabolic function are impaired, leading to mitochondrial damage and oxidative stress. Additionally, lower activation of Ulk1 in aging muscles may contribute to decreased autophagy flux and accumulation of dysfunctional mitochondria.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Geriatrics & Gerontology
Roberta Schellino, Marina Boido, Jan W. Vrijbloed, Ruggero G. Fariello, Alessandro Vercelli
Summary: Sarcopenia is the primary cause of impaired motor performance in the elderly. Inhibiting the myostatin system through ActR-Fc-nLG3 administration can enhance motor endurance and muscle strength in both young and old mice, potentially providing a treatment option for sarcopenia and other striatal muscle disorders.
Article
Geriatrics & Gerontology
Sue C. Bodine, Indranil Sinha, Hugh Lee Sweeney
Summary: Skeletal muscle undergoes significant changes with aging, leading to a loss of muscle mass and function. This is caused by various factors including alterations in proteostasis, mitochondrial function, extracellular matrix remodeling, and neuromuscular junction function. Factors such as acute illness and trauma contribute to the rate of sarcopenia. Repair and regeneration of skeletal muscle involve coordination between different cell populations, and targeting muscle macrophages with small molecules has shown promise in restoring muscle function. Disruptions in signaling pathways and cell communication contribute to the failure to repair and maintain muscle mass and function in aging and muscular dystrophies.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Min-Yi Wu, Wen-Jun Zou, Daehoon Lee, Lin Mei, Wen-Cheng Xiong
Summary: Sarcopenia, characterized by muscle mass and strength/function loss, is associated with neurodegenerative diseases like Alzheimer's disease (AD). The underlying mechanisms for their associations are not well understood. The APP gene encodes amyloid precursor protein (APP), enriched at neuromuscular junction (NMJ) and synapses in the central nervous system (CNS). This review highlights the physiological functions of APP and its family members and the pathological roles of Swedish mutant APP (APP(swe)) in muscles and NMJ, providing insights into neuromuscular diseases and AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Sarah K. Burke, Andrew Fenton, Yana Konokhova, Russell T. Hepple
Summary: Muscle atrophy in aging is most pronounced in fast twitch muscle like the gastrocnemius, with similar effects in the extensor digitorum longus and slow-twitch soleus, while the slow-twitch adductor longus increases in mass. Only the soleus shows significant alterations in fiber type with aging. Muscles that atrophy show an increased fraction of severely atrophic myofibers, while the adductor longus does not exhibit this phenomenon.
EXPERIMENTAL GERONTOLOGY
(2021)
Article
Cell Biology
Yoana Rabanal-Ruiz, Adam Byron, Alexander Wirth, Ralitsa Madsen, Lucia Sedlackova, Graeme Hewitt, Glyn Nelson, Julian Stingele, Jimi C. Wills, Tong Zhang, Andre Zeug, Reinhard Faessler, Bart Vanhaesebroeck, Oliver D. K. Maddocks, Evgeni Ponimaskin, Bernadette Carroll, Viktor Korolchuk
Summary: This study enhances our understanding of spatial regulation of mTORC1 by demonstrating that the localization of mTORC1 to focal adhesions is both necessary and sufficient for its activation by growth-promoting stimuli.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yann Cormerais, Milica Vucetic, Scott K. Parks, Jacques Pouyssegur
Summary: mTORC1 integrates signals to control biosynthetic processes in cancer cells, which are characterized by uncontrolled growth and proliferation. Amino acids are essential nutrients for cancer cell survival, as mTORC1 activity is particularly sensitive to intracellular amino acid levels. Targeting amino acid transporters could be a potential therapeutic strategy for cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Qiao Ding, Kaamini Kesavan, Kah Meng Lee, Elyse Wimberger, Thomas Robertson, Melinder Gill, Dominique Power, Jeryn Chang, Atefeh T. Fard, Jessica C. Mar, Robert D. Henderson, Susan Heggie, Pamela A. McCombe, Rosalind L. Jeffree, Michael J. Colditz, Massimo A. Hilliard, Dominic C. H. Ng, Frederik J. Steyn, William D. Phillips, Ernst J. Wolvetang, Shyuan T. Ngo, Peter G. Noakes
Summary: A defect in the n-agrin-LRP4-MuSK signaling pathway has been identified in muscle from MND patients for the first time. This signaling pathway plays a crucial role in maintaining the stability of the neuromuscular junction. These findings provide a potential therapeutic target for prolonging muscle function in MND patients.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Cell Biology
Jakob Proemer, Cinzia Barresi, Ruth Herbst
Summary: Muscle-specific kinase (MuSK) is the key regulator of neuromuscular junction development and its activation and signaling are tightly regulated. Recent studies using omics techniques have contributed to a better understanding of MuSK signaling. Impaired MuSK signaling causes muscle weakness, but the underlying pathophysiology is often unclear. This review focuses on recent advances in deciphering MuSK activation and downstream signaling, as well as the role of MuSK in non-muscle tissue.
CELLULAR SIGNALLING
(2023)
Review
Biochemistry & Molecular Biology
Adel E. E. Khairullin, Sergey N. N. Grishin, Ayrat U. U. Ziganshin
Summary: The purine signaling system, represented by purine and pyrimidine nucleotides and nucleosides, plays a role through the adenosine, P2X and P2Y receptor families. While P2 receptors have a minor role in physiological conditions, they become more significant in certain pathophysiological conditions, functioning as dominant signaling molecules. The diversity and distribution of P2 receptors make them an attractive target for new mechanism drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Matthew J. J. Fogarty, Obaid U. U. Khurram, Carlos B. B. Mantilla, Gary C. C. Sieck
Summary: The study suggests that chronic TrkB kinase inhibition in TrkB(F616) rats results in a significant worsening of diaphragm neuromuscular transmission, which acute BDNF treatment cannot rescue. Additionally, chronic TrkB kinase inhibition does not affect the apposition of pre-synaptic terminals and post-synaptic endplates at diaphragm NMJs.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Geriatrics & Gerontology
Anna Carolina Zaia Rodrigues, Zhong-Min Wang, Maria Laura Messi, Henry Jacob Bonilla, Liang Liu, Willard M. Freeman, Osvaldo Delbono
Summary: The study found that inducing the expression of Hand2 in sympathetic neurons in old mice can increase neuron size and number, improve muscle weight and force, enhance muscle innervation, promote muscle transmission, prevent inflammation, and maintain muscle protein synthesis.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2021)
Review
Biochemistry & Molecular Biology
Bisei Ohkawara, Mikako Ito, Kinji Ohno
Summary: This review focuses on secreted signaling molecules that regulate the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ), including neural agrin, Lrp4, MuSK, Rspo2, Fgf18, and Ctgf. These molecules play crucial roles in ensuring efficient signal transduction at the NMJ.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Edmund Battey, Regula Furrer, Jacob Ross, Christoph Handschin, Julien Ochala, Matthew J. Stroud
Summary: PGC-1α plays a critical role in myonuclear accretion during adaptation to endurance training, especially in larger muscle fibers. Myonuclear accretion in PGC-1α mKO mice is slightly affected with increasing fiber size, but is significantly altered in trained larger fibers compared to sedentary mice, highlighting the importance of PGC-1α in myonuclear accretion in these fibers.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Lukas Streese, Philippe Demougin, Paula Iborra, Alexander Kanitz, Arne Deiseroth, Julia M. Kropfl, Arno Schmidt-Trucksass, Mihaela Zavolan, Henner Hanssen
Summary: Untargeted profiling of circulating miRNAs in older adults revealed differential expression of 30 miRNAs among different health and disease groups. Increased expression of certain miRNAs was associated with higher metabolic risk and unfavorable health outcomes, while increased expression of others was linked to lower metabolic risk and favorable health indicators. Further studies are needed to validate these findings and explore the physiological and pathophysiological roles of miRNAs and their target genes in disease and health adaptation.
SCIENTIFIC REPORTS
(2022)
Article
Endocrinology & Metabolism
Emanuele Pignatti, Emre Murat Altinkilic, Konstantin Brautigam, Michael Grossl, Aurel Perren, Mihaela Zavolan, Christa E. Fluck
Summary: The study reveals that cholesterol deprivation plays a role in the maturation of the adrenocortical zona reticularis (zR) during adrenarche, leading to the reprogramming of steroidogenesis and decreased transcriptional activity of POU3F2.
Correction
Multidisciplinary Sciences
Daniel J. Ham, Anastasiya Borsch, Kathrin Chojnowska, Shuo Lin, Aurel B. Leuchtmann, Alexander S. Ham, Marco Thurkauf, Julien Delezie, Regula Furrer, Dominik Burri, Michael Sinnreich, Christoph Handschin, Lionel A. Tintignac, Mihaela Zavolan, Nitish Mittal, Markus A. Ruegg
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Daniel J. Ham, Anastasiya Boersch, Kathrin Chojnowska, Shuo Lin, Aurel B. Leuchtman, Alexander S. Ham, Marco Thuerkauf, Julien Delezie, Regula Furrer, Dominik Burri, Michael Sinnreich, Christoph Handschin, Lionel A. Tintignac, Mihaela Zavolan, Nitish Mittal, Markus A. Rueegg
Summary: The anti-aging intervention calorie restriction (CR) is thought to act via the nutrient-sensing multiprotein complex mTORC1. However, this study showed that the mTORC1-inhibitor rapamycin and CR use largely distinct mechanisms to slow mouse muscle aging.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Manuel Blandino-Rosano, Joshua O. Scheys, Joao Pedro Werneck-de-Castro, Ruy A. Louzada, Joana Almaca, Gil Leibowitz, Markus A. Ruegg, Michael N. Hall, Ernesto Bernal-Mizrachi
Summary: This study reveals that mTORC2 regulates glucose-stimulated insulin secretion by promoting actin filament remodeling, and GLP-1 can rescue defects in insulin secretion by improving actin polymerization in the beta islets.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Review
Neurosciences
Regula Furrer, Christoph Handschin
Summary: Ageing is a biological process linked to functional decline and death. There are differences in life- and healthspan, representing life expectancy and years without major diseases. The genetic and molecular mechanisms of ageing and its connection to diseases are still poorly understood. However, there are compounds that can affect this process. This review discusses pharmacological and non-pharmacological anti-ageing approaches, as well as strategies to mitigate age-related pathologies and extend life- and healthspan.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Review
Physiology
Regula Furrer, John A. Hawley, Christoph Handschin
Summary: Human skeletal muscle exhibits remarkable plasticity, adapting to various external stimuli, including contractile loading. However, our understanding of the cellular and molecular mechanisms governing muscle plasticity across different exercise levels is incomplete. As a result, training methods for elite athletes are often based on trial and error, with post hoc scientific research being informed by successful coaches and athletes' experiences. This review provides an overview of morphological and functional changes, as well as molecular mechanisms underlying exercise adaptation, with a focus on genetic and individual differences in exercise capacity and performance, particularly in aging athletes. Overall, it comprehensively explores skeletal muscle plasticity in response to different modes of exercise and its translation from molecules to medals.
PHYSIOLOGICAL REVIEWS
(2023)
Article
Endocrinology & Metabolism
Svenia Schmid, Barbara Heim-Kupr, Joaquin Perez-Schindler, Shivani Mansingh, Markus Beer, Nitish Mittal, Nikolaus Ehrenfeuchter, Christoph Handschin
Summary: This study reveals the role of PGC-1β in the regulation of catabolic pathways in muscle-specific loss-of-function mouse models. PGC-1β plays a crucial role in protein breakdown, muscle mass preservation, and function.
MOLECULAR METABOLISM
(2022)
Article
Physiology
Aurel B. Leuchtmann, Yasmine Afifi, Danilo Ritz, Christoph Handschin
Summary: Exercise promotes and preserves various functions in the body but the molecular mechanisms behind these adaptations are not well understood. To study specific exercise adaptations, standardized training interventions are necessary. In this study, we examined the changes and adaptations in mice following low-resistance and high-resistance wheel running. Both groups showed improvements in body composition and oxygen uptake, but there were differences in running performance and muscle strength between the two interventions. Thus, the study suggests that different training modalities have varying effects on specific aspects of fitness.
PHYSIOLOGICAL REPORTS
(2023)
Article
Multidisciplinary Sciences
Laura M. de Smalen, Anastasiya Borsch, Aurel B. Leuchtmann, Jonathan F. Gill, Danilo Ritz, Mihaela Zavolan, Christoph Handschin
Summary: Sarcopenia, the age-related loss of skeletal muscle mass and function, can significantly impact quality of life and mortality. This study found that mitochondrial proteostasis plays an important role in muscle aging and highlights the positive effects of exercise on mitochondrial protein synthesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Marco Thurkauf, Shuo Lin, Filippo Oliveri, Dirk Grimm, Randall J. Platt, Markus A. Ruegg
Summary: This study establishes a highly efficient somatic gene deletion system by combining Cre-mediated skeletal muscle fiber-specific Cas9 expression with myotropic adeno-associated virus-mediated sgRNA delivery. Using this system, specific genes can be locally or systemically inactivated, replicating the phenotype of traditional gene-knockout mouse models and unraveling the function of individual genes or entire signaling pathways in adult skeletal muscle fibers.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Judith R. Reinhard, Emanuela Porrello, Shuo Lin, Pawel Pelczar, Stefano C. Previtali, Markus A. Ruegg
Summary: LAMA2-related muscular dystrophy is a severe congenital muscular dystrophy caused by mutations in the LAMA2 gene. Expressing mini-agrin and alpha LNNd proteins in mice can improve the condition and prevent hind limb paralysis, which are the most affected areas in LAMA2 MD. This research is crucial for developing gene therapy for LAMA2 MD patients.