title: Lower antioxidant capacity and elevated p53 and p21 may be a link between gender disparity in renal telomere shortening, albuminuria, and longevity.
abstract: It is well documented that females live longer than males and more renal damage occurs in males. However, the underlying mechanisms are not fully understood. The aim of this study was to define aging effects on albuminuria and kidney telomere length from male and female rats and to determine mechanisms, which may explain any observed differences. Cellular senescence is known to play a major role in nephropathology, and as such, a range of senescence markers were compared in male and female renal tissue. Oxidative stress has been shown to accelerate telomere shortening and elicit cellular growth arrest. Thus major antioxidants, MnSOD, glutathione peroxidase I, and glutathione reductase, were also evaluated. Urinary albumin excretion increased with age in both sexes, but the increase was greater in males than females. In the cortex and medulla of both male and female rats, age-related telomere shortening occurred, the effect being more pronounced in males than in females. The cortical region had more short telomeres than the medulla in both genders. p53 And p21 expression over time significantly increased in males, but not in females. MnSOD expression was elevated in female vs. male cortex. Gxp1 and glutathione reductase levels were increased in the older female cortex compared with males. Our findings indicate that a reduction in oxidative damage protection may be responsible for accelerated telomere shortening over time, resulting in increased cellular senescence, loss of renal function, and death in male rats.
authors.affiliation: Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Box 232, Hills Road, Cambridge, CB2 2QR, UK. jane.adkins@ntlworld.com
authors.forename: Jane L
authors.initials: JL
authors.lastname: Tarry-Adkins
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
authors.forename: Anthony
authors.initials: A
authors.lastname: Norden
authors.forename: Hanane
authors.initials: H
authors.lastname: Cherif
authors.forename: C Nicholas
authors.initials: CN
authors.lastname: Hales
mesh_terms: D000419:Albuminuria / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007672:Kidney Cortex / Q000201:enzymology / Q000378:metabolism*; D007679:Kidney Medulla / Q000201:enzymology / Q000378:metabolism*; D008136:Longevity; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D015238:Sulfotransferases; D013482:Superoxide Dismutase / Q000378:metabolism; D016615:Telomere / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D002135:Calcium-Binding Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat