title: Reactive oxygen species production and mitochondrial dysfunction in white blood cells are not valid biomarkers of ageing in the very old.
abstract: Reliable and valid biomarkers of ageing (BoA) are needed to understand mechanisms, test interventions and predict the timing of adverse health events associated with ageing. Since increased reactive oxygen species (ROS) production and mitochondrial dysfunction are consequences of cellular senescence and may contribute causally to the ageing of organisms, we focused on these parameters as candidate BoA. Superoxide levels, mitochondrial mass and mitochondrial membrane potential in human peripheral blood mononuclear cells (PBMCs) and subpopulations (lymphocytes and monocytes) were measured in participants from the Newcastle 85+ study, a population-based study of the very old (aged 85 years and older). The intra- and inter-assay precision expressed as coefficient of variation (CV) for all parameters was acceptable (3% to 12% and 5 to 22% respectively). All parameters were stable in the short-term (1 week interval) in a sample of control individuals in the PBMCs and lymphocyte subpopulation, however they were unstable in the monocyte subpopulation; this rendered monocytes unreliable for further analysis. There was a significant association between superoxide levels and mitochondrial mass (positive in lymphocytes, p = 0.01) and between superoxide levels and mitochondrial membrane potential (negative in PBMCs, p = 0.01; positive in lymphocytes, p = 0.05). There were also significant associations between superoxide levels and mitochondrial parameters with other markers of oxidative stress-induced cellular senescence (p≤0.04), however some were in the opposite direction to expected. No associations were found between the measured parameters and age-related outcomes, including cognitive impairment, disability, co-morbidity and survival - questioning the validity of these parameters as candidate BoA in the very old.
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Wiley
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Deepthi
authors.initials: D
authors.lastname: Ashok
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martin-Ruiz
authors.affiliation: Unilever Discover, Colworth Science Park, Sharnbrook, Bedfordshire, United Kingdom.
authors.forename: Duncan C S
authors.initials: DC
authors.lastname: Talbot
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Collerton
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kingston
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Davies
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Catt
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Carol
authors.initials: C
authors.lastname: Jagger
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Thomas B L
authors.initials: TB
authors.lastname: Kirkwood
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: von Zglinicki
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D002470:Cell Survival; D016922:Cellular Senescence; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015203:Reproducibility of Results; D013481:Superoxides / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D013481:Superoxides