acids (Sohal and Weindruch, 1996). However, physical function is also a crucial component of healthy aging and longevity (Newman et al., 2001) and it is strongly related to the oxidative stress pathway (Sastre et al., 2003). In fact, physical performance has been reported to be associated with specific genetic variants related to oxidative stress in middle-aged people (Hadjigeorgiou et al., 2012; Gomez-Cabrera et al., 2008) and in elderly people (Dato et al., 2012a; Soerensen et al., 2012). Therefore, investigating the association between genetic variability in the proantioxidant pathways and functional status in very old age may be a promising strategy to identify new molecular markers of longevity, as well as potential targets for intervention to promote healthy aging. In this paper, we analyzed the association of 38 genes (311 SNPs) belonging to the proantioxidant pathways with physical and cognitive performances, by analyzing single SNP and gene-based associations with Hand Grip strength (HG), Activities of Daily Living (ADL), Walking Speed (WS), Mini Mental State Examination (MMSE) and Composite Cognitive Score (CCS) in a Cohort of 1089 Danish nonagenarians. Moreover, for each gene analyzed in the proantioxidant pathway, we tested the influence on longitudinal survival. Our results suggest that genetic variability in the proantioxidant pathway is able to modulate physical and cognitive performance after the ninth decade of life, finally influencing extreme survival.Acids, which are susceptible to lipid peroxidation (Halliwell, 2006), play a role in cognitive ability in older individuals. Studies have found that apolipoprotein E (APOE), catechol-O-methyl transferase (COMT), brain-derived neurotrophic factor (BDNF), and dystrobrevin binding protein 1 (DTNBP1) genes are involved in cognitive ability in older individuals, but these studies did not consider very old subjects. The sample population analyzed was aged around 85 years as a maximum (De Blasi et al., 2009; Lindenberger et al., 2008). ADL refers to Activity Daily Living, HG to Hand Grip, BMI to Body Mass Index, MMSE to Mini Mental State Examination, and CCS to Composite Cognitive Score. Survival data were calculated from a 12-year follow-up period. Participants were defined as not disabled if they were independent in all items and disabled if they were dependent in at least one item. Briefly, this population-based survey started in 1998 when 2,262 of the participants were 92-93.82 years of age (mean age 93.2). Survivors were subsequently re-assessed in 2000, 2003, and 2005 (Christensen et al., 2008; Nybo et al., 2001, 2003). Home-based questionnaires were submitted for the collection of socio-demographic information, assessment of physical, cognitive, depressive status, sensory impairments, medications, self-reported health status. DNA was sampled for each subject participating in the survey. Vital status was followed until death or January 1st, 2013, whichever came first. The mean follow-up time for survivors was 13.4 years (range: 13.2-13.6). Information on survival status was retrieved from the Danish Central Population Register (Pedersen et al., 2006). Preservation of functional ability, together with cognitive performance, is a well-recognized marker of longevity (Schupf et al., 2004). Consistently, predictors of functional status such as HG and disability are key components of frailty definition in old age (Dato et al., 2012a). Furthermore, analyses of longitudinal cohorts of Danish nonagenarians demonstrated that exceptional longevity does not result in excessive levels of disability (Christensen et al., 2008), suggesting a relationship between the general increase of life expectancy with good maintenance of individual activities of daily living. This evidence supports the hypothesis that factors influencing increased survival can also influence disability levels in older cohorts (Engberg et al., 2008), and so longevity and lower disability levels may have common causes at the organismal level. Permission to collect blood samples and usage of register-based information was granted by The Danish National Committee on Biomedical Research Ethics for both initial and follow-up study. In this study, we investigated the association between 311 single nucleotide polymorphisms (SNPs) at 38 genes belonging to the oxidative stress pathway with functional status at very old age through a gene-based approach. To this purpose, we analyzed 1,089 Danish nonagenarians drawn from the longitudinal 1905 Cohort Study, a well-characterized (Christensen et al., 2009; Nybo et al., 2001, 2003) and very suitable sample for genotype-phenotype association studies (Dato et al., 2010; Soerensen et al., 2010, 2012a,b, 2013) for the associations with physical and cognitive parameters. Physical parameters were represented by HG strength, ADL, WS, and cognitive parameters by MMSE and CCS.