Navarro 2024 Exp Gerontol
| Navarro CDC, Francisco A, Costa EFD, Dalla Costa AP, Sartori MR, Bizerra PFV, Salgado AR, Figueira TR, Vercesi AE, Castilho RF (2024) Aging-dependent mitochondrial bioenergetic impairment in the skeletal muscle of NNT-deficient mice. Exp Gerontol 193:112465. https://doi.org/10.1016/j.exger.2024.112465 |
Navarro Claudia DC, Francisco Annelise, Costa Ericka FD, Dalla Costa Ana P, Sartori Marina R, Bizerra Paulo FV, Salgado Andreia R, Figueira Tiago R, Vercesi Anibal E, Castilho Roger F (2024) Exp Gerontol
Abstract: 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. • Keywords: Age-related muscle dysfunction, Locomotor impairment, Mitochondrial bioenergetics, NNT deficiency, Nicotinamide nucleotide transhydrogenase, Oxidative stress • Bioblast editor: Plangger M • O2k-Network Lab: BR Campinas Castilho R
Labels: MiParea: Respiration, Genetic knockout;overexpression
Pathology: Aging;senescence
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: ET, LEAK, OXPHOS
Pathway: N, S, CIV, ROX
HRR: Oxygraph-2k
2024-05
