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Aging-dependent mit...
Aging-dependent mitochondrial bioenergetic impairment in the skeletal muscle of NNT-deficient mice
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- Navarro, Claudia D.C. (author)
- University of Campinas
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- Francisco, Annelise (author)
- Lund University,Lunds universitet,Diabetes och hjärnans funktion,Forskargrupper vid Lunds universitet,Diabetes and Brain Function,Lund University Research Groups,University of Campinas
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- Costa, Ericka F.D. (author)
- University of Campinas
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- Dalla Costa, Ana P. (author)
- University of Campinas
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- Sartori, Marina R. (author)
- University of Campinas
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- Bizerra, Paulo F.V. (author)
- University of Campinas
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- Salgado, Andréia R. (author)
- University of Campinas
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- Figueira, Tiago R. (author)
- University of São Paulo
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- Vercesi, Anibal E. (author)
- University of Campinas
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- Castilho, Roger F. (author)
- University of Campinas
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Experimental Gerontology. - 0531-5565. ; 193
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Keyword
- Age-related muscle dysfunction
- Locomotor impairment
- Mitochondrial bioenergetics
- Nicotinamide nucleotide transhydrogenase
- NNT deficiency
- Oxidative stress
Publication and Content Type
- art (subject category)
- ref (subject category)
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Navarro, Claudia ...
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Francisco, Annel ...
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Costa, Ericka F. ...
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Dalla Costa, Ana ...
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Sartori, Marina ...
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Bizerra, Paulo F ...
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Salgado, Andréia ...
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Figueira, Tiago ...
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Vercesi, Anibal ...
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Castilho, Roger ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
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Experimental Ger ...
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Lund University