RT Journal Article T1 Markers of Mitochondrial Function and DNA Repair Associated with Physical Function in Centenarians A1 Sánchez-Román Rojas, Inés A1 Ferrando, Beatriz A1 Myrup Holst, Camilla A1 Mengel-From, Jonas A1 Hoei Rasmussen, Signe A1 Thinggaard, Mikael A1 Bohr, Vilhelm A. A1 Christensen, Kaare A1 Stevnsner, Tinna AB 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. PB MDPI SN 2218-273X YR 2024 FD 2024-07-26 LK https://hdl.handle.net/20.500.14352/115374 UL https://hdl.handle.net/20.500.14352/115374 LA eng NO Sánchez Román, I., Ferrando Forés, B., Myrup Holst, C., Mengel-From, J., Hoei Rasmussen, S., Thinggaard, M., Bohr, V. A., Christensen, K., & Stevnsner, T. (2024). Markers of Mitochondrial Function and DNA Repair Associated with Physical Function in Centenarians. Biomolecules, 14(8), 909. https://doi.org/10.3390/BIOM14080909 NO The work was supported by the Novo Nordisk Foundation; the Faculty of Health Sciences, University of Southern Denmark; The Health Foundation (Helsefonden) (Grant nr. 16-B-0271); the Danish Interdisciplinary Research Council and the Intramural Program of the National Institute on Aging, NIH, USA. The Danish Aging Research Center is supported by a grant from the Velux Foundation. NO Novo Nordisk Foundation NO University of Southern Denmark NO The Health Foundation (Dinamarca) NO Danish Interdisciplinary Research Council NO National Institute on Aging NO The Danish Aging Research Center NO The Velux Foundation DS Docta Complutense RD 6 abr 2025