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

• Published in: Biomolecules (Basel, Switzerland) Vol. 14; no. 8; p. 909
• Main Authors: Sanchez-Roman, Ines, Ferrando, Beatriz, Myrup Holst, Camilla, Mengel-From, Jonas, Hoei Rasmussen, Signe, Thinggaard, Mikael, Bohr, Vilhelm A, Christensen, Kaare, Stevnsner, Tinna
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.07.2024; MDPI
• Subjects: Activities of daily living; Age; Aged, 80 and over; Aging; Aging - genetics; Bioenergetics; Biomarkers; Biomarkers - blood; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - blood; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Centenarians; Cognitive ability; Copy number; Disability; DNA; DNA Copy Number Variations; DNA damage; DNA repair; DNA Repair - genetics; DNA, Mitochondrial - genetics; DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics; DNA-(Apurinic or Apyrimidinic Site) Lyase - metabolism; Elbow; Electron transport; Energy Metabolism - genetics; Ethylenediaminetetraacetic acid; Female; Frailty; Genomic instability; Geriatrics; grip strength; Hand Strength; Humans; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Male; mitochondria; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial DNA; NAD - blood; NAD - metabolism; Oldest old people; Oxygen consumption; Oxygen Consumption - genetics; Peripheral blood mononuclear cells; Pharmaceutical industry; physical function; Protein Carbonylation; Respiration; Denmark; United States; Germany; grip strength; physical function; DNA repair; mitochondria; centenarians
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom14080909

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 ( < 0.05). In centenarian females, grip strength had a positive association with mtDNA copy number ( < 0.05), and a borderline positive trend for activity of the central DNA repair enzyme, APE 1 ( = 0.075), while a negative trend was found with circulating protein carbonylation ( = 0.07) in the entire cohort. Lastly, a trend was observed for a negative association between BDNF and activity of daily living disability score ( = 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.