Aging-dependent mitochondrial bioenergetic impairment in the skeletal muscle of NNT-deficient mice.

Autor: Navarro CDC; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), 13083 887 Campinas, SP, Brazil., Francisco A; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), 13083 887 Campinas, SP, Brazil; Department of Experimental Medical Science, Faculty of Medicine, Lund University, 221 84 Lund, Sweden., Costa EFD; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), 13083 887 Campinas, SP, Brazil., Dalla Costa AP; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), 13083 887 Campinas, SP, Brazil., Sartori MR; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), 13083 887 Campinas, SP, Brazil., Bizerra PFV; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), 13083 887 Campinas, SP, Brazil., Salgado AR; Multidisciplinary Center for Biological Investigation on Laboratory Animals Science, University of Campinas, Campinas, SP, Brazil., Figueira TR; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo, 14040 900 Ribeirão Preto, SP, Brazil., Vercesi AE; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), 13083 887 Campinas, SP, Brazil., Castilho RF; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), 13083 887 Campinas, SP, Brazil. Electronic address: rogerc@unicamp.br.
Jazyk: angličtina
Zdroj: Experimental gerontology [Exp Gerontol] 2024 Aug; Vol. 193, pp. 112465. Date of Electronic Publication: 2024 May 25.
DOI: 10.1016/j.exger.2024.112465
Abstrakt: Overall health relies on features of skeletal muscle that generally decline with age, partly due to mechanisms associated with mitochondrial redox imbalance and bioenergetic dysfunction. Previously, aged mice genetically devoid of the mitochondrial NAD(P) + transhydrogenase (NNT, encoded by the nicotinamide nucleotide transhydrogenase gene), an enzyme involved in mitochondrial NADPH supply, were shown to exhibit deficits in locomotor behavior. Here, by using young, middle-aged, and older NNT-deficient (Nnt -/- ) mice and age-matched controls (Nnt +/+ ), we aimed to investigate how muscle bioenergetic function and motor performance are affected by NNT expression and aging. Mice were subjected to the wire-hang test to assess locomotor performance, while mitochondrial bioenergetics was evaluated in fiber bundles from the soleus, vastus lateralis and plantaris muscles. An age-related decrease in the average wire-hang score was observed in middle-aged and older Nnt -/- mice compared to age-matched controls. Although respiratory rates in the soleus, vastus lateralis and plantaris muscles did not significantly differ between the genotypes in young mice, the rates of oxygen consumption did decrease in the soleus and vastus lateralis muscles of middle-aged and older Nnt -/- mice. Notably, the soleus, which exhibited the highest NNT expression level, was the muscle most affected by aging, and NNT loss. Additionally, histology of the soleus fibers revealed increased numbers of centralized nuclei in older Nnt -/- mice, indicating abnormal morphology. In summary, our findings suggest that NNT expression deficiency causes locomotor impairments and muscle dysfunction during aging in mice.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that have or could be perceived to have influenced the work reported in this article.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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