Markers of Mitochondrial Function and DNA Repair Associated with Physical Function in Centenarians

  1. Sánchez Román, Inés 12
  2. Ferrando Forés, Beatriz 125
  3. Myrup Holst, Camilla 12
  4. Mengel-From, Jonas 23
  5. Hoei Rasmussen, Signe 234
  6. Thinggaard, Mikael 23
  7. Bohr, Vilhelm A. 6
  8. Christensen, Kaare 23
  9. Stevnsner, Tinna 12
  1. 1 Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark
  2. 2 Danish Aging Research Center, Department of Public Health, University of Southern Denmark, 5230 Odense, Denmark
  3. 3 Epidemiology, Biostatistics and Biodemography, University of Southern Denmark, 5230 Odense, Denmark
  4. 4 Geriatric Research Unit, Department of Clinical Research, University of Southern Denmark, 5230 Odense, Denmark
  5. 5 Facultad de Humanidades y Ciencias Sociales, Universidad Isabel I, 09003 Burgos, Spain
  6. 6 Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
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Revista:
Biomolecules

ISSN: 2218-273X

Año de publicación: 2024

Volumen: 14

Número: 8

Páginas: 909

Tipo: Artículo

DOI: 10.3390/BIOM14080909 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Biomolecules

Resumen

Mitochondrial dysfunction and genomic instability are key hallmarks of aging. The aim of this study was to evaluate whether maintenance of physical capacities at very old age is associated with key hallmarks of aging. To investigate this, we measured mitochondrial bioenergetics, mitochondrial DNA (mtDNA) copy number and DNA repair capacity in peripheral blood mononuclear cells from centenarians. In addition, circulating levels of NAD+/NADH, brain-derived neurotrophic factor (BDNF) and carbonylated proteins were measured in plasma and these parameters were correlated to physical capacities. Centenarians without physical disabilities had lower mitochondrial respiration values including ATP production, reserve capacity, maximal respiration and non-mitochondrial oxygen-consumption rate and had higher mtDNA copy number than centenarians with moderate and severe disabilities (p < 0.05). In centenarian females, grip strength had a positive association with mtDNA copy number (p < 0.05), and a borderline positive trend for activity of the central DNA repair enzyme, APE 1 (p = 0.075), while a negative trend was found with circulating protein carbonylation (p = 0.07) in the entire cohort. Lastly, a trend was observed for a negative association between BDNF and activity of daily living disability score (p = 0.06). Our results suggest that mechanisms involved in maintaining mitochondrial function and genomic stability may be associated with maintenance of physical function in centenarians.

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Información de financiación

Financiadores

  • Novo Nordisk Foundation
  • Faculty of Health Sciences, University of Southern Denmark
  • The Health Foundation
    • 16-B-0271
  • Danish Interdisciplinary Research Council
  • National Institute on Aging
  • Velux Foundation

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