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Molecular and Neuromuscular Mechanisms in Skeletal Muscle Aging

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 1427

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Department of Neuroscience, Imaging and Clinical Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
Interests: muscle; skeletal
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is known that in humans, skeletal muscles account for about 40% of the body weight and are essential for overall health. With increasing age, muscle function declines, causing reduced mobility, thus leading to reduced independence and an increase in morbidity and mortality in the elderly. This age-related decline in muscle function is known as sarcopenia. Sarcopenia is a multifactorial disease that is defined as a progressive loss of muscle mass, strength, and function. It has attracted great research efforts to clarify its underlying mechanisms and potential treatments.

When aiming to discover hallmarks of aging, looking at shared age- and disease-related changes in cellular and muscular pathways such as apoptosis, cell cycle regulation, calcium handling, myokines, and catabolism can be helpful.

The aim of this Special Issue is essentially to collect new discoveries and study approaches to aging processes, mainly at the molecular and neuromuscular levels. For this Special Issue, we invite researchers to provide original research articles and review articles regarding results in the field of the new frontiers that can contribute to the understanding of the aging muscle process.

Dr. Rosa Mancinelli
Guest Editor

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Keywords

  • aging
  • sarcopenia
  • neuromuscular junction
  • molecular muscle modifications
  • myokines

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Published Papers (2 papers)

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Research

19 pages, 21062 KiB  
Article
Functional and Structural Changes in Diaphragm Neuromuscular Junctions in Early Aging
by Andrei N. Tsentsevitsky, Guzel V. Sibgatullina, Yulia G. Odoshivkina, Venera F. Khuzakhmetova, Anna R. Tokmakova, Anastasia A. Ponomareva, Vadim V. Salnikov, Guzalia F. Zakirjanova, Alexey M. Petrov and Ellya A. Bukharaeva
Int. J. Mol. Sci. 2024, 25(16), 8959; https://doi.org/10.3390/ijms25168959 - 17 Aug 2024
Viewed by 474
Abstract
Age-related impairment of the diaphragm causes respiratory complications. Neuromuscular junction (NMJ) dysfunction can be one of the triggering events in diaphragm weaknesses in old age. Prominent structural and functional alterations in diaphragm NMJs were described in elderly rodents, but NMJ changes in middle [...] Read more.
Age-related impairment of the diaphragm causes respiratory complications. Neuromuscular junction (NMJ) dysfunction can be one of the triggering events in diaphragm weaknesses in old age. Prominent structural and functional alterations in diaphragm NMJs were described in elderly rodents, but NMJ changes in middle age remain unclear. Here, we compared diaphragm muscles from young adult (3 months) and middle-aged (12 months) BALB/c mice. Microelectrode recordings, immunofluorescent staining, electron microscopy, myography, and whole-body plethysmography were used. We revealed presynaptic (i) and postsynaptic (ii) changes. The former (i) included an increase in both action potential propagation velocity and neurotransmitter release evoked by low-, moderate-, and high-frequency activity but a decrease in immunoexpression of synapsin 1 and synaptic vesicle clustering. The latter (ii) consisted of a decrease in currents via nicotinic acetylcholine receptors and the area of their distribution. These NMJ changes correlated with increased contractile responses to moderate- to high-frequency nerve activation. Additionally, we found alterations in the pattern of respiration (an increase in peak inspiratory flow and a tendency of elevation of the tidal volume), which imply increased diaphragm activity in middle-aged mice. We conclude that enhancement of neuromuscular communication (due to presynaptic mechanism) accompanied by improved contractile responses occurs in the diaphragm in early aging. Full article
(This article belongs to the Special Issue Molecular and Neuromuscular Mechanisms in Skeletal Muscle Aging)
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27 pages, 3498 KiB  
Article
Molecular Adaptations of BDNF/NT-4 Neurotrophic and Muscarinic Pathways in Ageing Neuromuscular Synapses
by Marta Balanyà-Segura, Aleksandra Polishchuk, Laia Just-Borràs, Víctor Cilleros-Mañé, Carolina Silvera, Anna Ardévol, Marta Tomàs, Maria A. Lanuza, Erica Hurtado and Josep Tomàs
Int. J. Mol. Sci. 2024, 25(15), 8018; https://doi.org/10.3390/ijms25158018 - 23 Jul 2024
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Abstract
Age-related conditions, such as sarcopenia, cause physical disabilities for an increasing section of society. At the neuromuscular junction, the postsynaptic-derived neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NT-4) have neuroprotective functions and contribute to the correct regulation of the exocytotic machinery. [...] Read more.
Age-related conditions, such as sarcopenia, cause physical disabilities for an increasing section of society. At the neuromuscular junction, the postsynaptic-derived neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NT-4) have neuroprotective functions and contribute to the correct regulation of the exocytotic machinery. Similarly, presynaptic muscarinic signalling plays a fundamental modulatory function in this synapse. However, whether or not these signalling pathways are compromised in ageing neuromuscular system has not yet been analysed. The present study analyses, through Western blotting, the differences in expression and activation of the main key proteins of the BDNF/NT-4 and muscarinic pathways related to neurotransmission in young versus ageing Extensor digitorum longus (EDL) rat muscles. The main results show an imbalance in several sections of these pathways: (i) a change in the stoichiometry of BDNF/NT-4, (ii) an imbalance of Tropomyosin-related kinase B receptor (TrkB)-FL/TrkB-T1 and neurotrophic receptor p 75 (p75NTR), (iii) no changes in the cytosol/membrane distribution of phosphorylated downstream protein kinase C (PKC)βI and PKCε, (iv) a reduction in the M2-subtype muscarinic receptor and P/Q-subtype voltage-gated calcium channel, (v) an imbalance of phosphorylated mammalian uncoordinated-18-1 (Munc18-1) (S313) and synaptosomal-associated protein 25 (SNAP-25) (S187), and (vi) normal levels of molecules related to the management of acetylcholine (Ach). Based on this descriptive analysis, we hypothesise that these pathways can be adjusted to ensure neurotransmission rather than undergoing negative alterations caused by ageing. However, further studies are needed to assess this hypothetical suggestion. Our results contribute to the understanding of some previously described neuromuscular functional age-related impairments. Strategies to promote these signalling pathways could improve the neuromuscular physiology and quality of life of older people. Full article
(This article belongs to the Special Issue Molecular and Neuromuscular Mechanisms in Skeletal Muscle Aging)
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