title: Oxidative stress and frailty: A systematic review and synthesis of the best evidence.
abstract: OBJECTIVE
  Oxidative stress (OS) is associated with accelerated aging. Previous studies have suggested a possible relationship between OS and frailty but this association remains unclear. We conducted a systematic review to investigate potential interactions between OS and frailty.
  
  
  METHODS
  A systematic literature search of original reports providing data on 'OS and antioxidant' parameters and frailty was carried out across major electronic databases from inception until May 2016. Cross-sectional/case control and longitudinal studies reporting data on the association between frailty and anti-oxidants-OS biomarkers were considered for inclusion. Results were summarized with a synthesis based on the best evidence.
  
  
  RESULTS
  From 1856 hits, 8 studies (cross-sectional/case control) were included (N=6349; mean age of 75±12years; 56.4% females). Overall, there were 588 (=9.3%) frail, 3036 pre-frail (=47.8%), 40 (=0.6%) pre-frail/robust, and 2685 (=42.3%) robust subjects. Six cross-sectional/case control studies demonstrated that frailty was associated with an increase in peripheral OS biomarkers, including lipoprotein phospholipase A2 (1 study), isoprostanes (2 studies), malonaldehyde (2 studies), 8-hydroxy-20-deoxyguanosine (2 studies), derivate of reactive oxygen metabolites (2 studies), oxidized glutathione/glutathione (1 study), 4-hydroxy-2,3-nonenal (1 study), and protein carbonylation levels (1 study). In addition, preliminary evidence points to lower anti-oxidant parameters (vitamin C, E, α-tocopherol, biological anti-oxidant potential, total thiol levels) in frailty.
  
  
  CONCLUSIONS
  Frailty and pre-frailty appear to be associated with higher OS and possibly lower anti-oxidant parameters. However, due to the cross-sectional design, it is not possible to disentangle the directionality of the relationships observed. Thus, future high-quality and in particular longitudinal research is required to confirm or refute these relationships and to further elucidate pathophysiological mechanisms.
authors.affiliation: Kayseri Education and Research Hospital, Geriatric Center, Kayseri, Turkey; Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London Box SE5 8AF, United Kingdom.
authors.forename: Pinar
authors.initials: P
authors.lastname: Soysal
authors.affiliation: Center for Aging Brain and Dementia, Department of Geriatric Medicine, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey; Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London Box SE5 8AF, United Kingdom.
authors.forename: Ahmet Turan
authors.initials: AT
authors.lastname: Isik
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London Box SE5 8AF, United Kingdom.
authors.forename: Andre F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, Geelong, Australia; Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London Box SE5 8AF, United Kingdom.
authors.forename: Brisa S
authors.initials: BS
authors.lastname: Fernandes
authors.affiliation: Department of Neurosciences, University of Padova, Padova, Italy; National Health Care System, Padova Local Unit ULSS 17, Italy; Institute for Clinical Research and Education in Medicine, I.R.E.M., Padua, Italy; Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London Box SE5 8AF, United Kingdom.
authors.forename: Marco
authors.initials: M
authors.lastname: Solmi
authors.affiliation: Health, Social Care and Education, Anglia Ruskin University, Chelmsford, United Kingdom; Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London Box SE5 8AF, United Kingdom.
authors.forename: Patricia
authors.initials: P
authors.lastname: Schofield
authors.affiliation: Institute for Clinical Research and Education in Medicine, I.R.E.M., Padua, Italy; Geriatrics Division, Department of Medicine-DIMED, University of Padova, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Veronese
authors.affiliation: Health, Social Care and Education, Anglia Ruskin University, Chelmsford, United Kingdom; Institute of Clinical Research and Education in Medicine (IREM), Padova, Italy; Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AZ, United Kingdom; Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London Box SE5 8AF, United Kingdom. Electronic address: Brendon.stubbs@kcl.ac.uk.
authors.forename: Brendon
authors.initials: B
authors.lastname: Stubbs
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D003430:Cross-Sectional Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D016330:Frail Elderly; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D028421:Isoprostanes / Q000378:metabolism; D008137:Longitudinal Studies; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D000447:Aldehydes; D015415:Biomarkers; D028421:Isoprostanes; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D000080242:8-Hydroxy-2'-Deoxyguanosine; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D003849:Deoxyguanosine; D005978:Glutathione; D024502:alpha-Tocopherol; C027576:4-hydroxy-2-nonenal; D019803:Glutathione Disulfide
keywords: Anti-oxidant; Frail; Frailty; Oxidative stress