The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old.
The free radical theory of aging states that reactive oxygen species (ROS) play a key role in age-related accumulation of cellular damage, and consequently influence aging and longevity. Therefore, variation in genes encoding proteins protecting against ROS could be expected to influence variation in aging and life span. The rs4880 and rs1050450 SNPs in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase 1 (GPX1) genes, respectively, are associated with age-related diseases and appear to affect the activities of the encoded variant proteins. In this study we genotyped these SNPs in 1650 individuals from the Danish 1905 cohort (follow-up time: 1998-2008, age at intake: 92-93 years, number of deaths: 1589 (96.3%)) and investigated the association with aging and longevity. We found decreased mortality of individuals holding either the MnSOD rs4880 C or the GPX1 rs1050450 T alleles (HR (MnSOD(CC/CT))=0.91, P=0, p=0.002 and HR (GPX1(TT/TC))=0.93, p=0.008). Furthermore, a synergetic effect of the alleles was observed (HR=0.76, p=0.001). Finally, moderate positive associations with good self rated health, decreased disability and increased cognitive capacity were observed. Our results thus indicate that genetic variation in MnSOD and GPX1 may be associated with aging and longevity.
Soerensen
Mette
M
Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark. msoerensen@health.sdu.dk
Christensen
Kaare
K
Stevnsner
Tinna
T
Christiansen
Lene
L
D000369:Aged, 80 and over; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D005787:Gene Frequency; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000235:genetics*; D000094765:Glutathione Peroxidase GPX1
D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human