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Aging and its aligned loss of muscle mass are associated with higher levels of DNA damage and deteriorated antioxidant defence. To improve the body's overall resistance against DNA damage, maintaining a healthy and active lifestyle is desirable, especially in the elderly. As people age, many have to change their residence from home living to an institution, which is often accompanied by malnutrition, depression and inactivity. The current study aimed at investigating the effect of a 6-month progressive resistance training (RT), with or without protein and vitamin supplementation (RTS), or cognitive training (CT), on DNA strand breaks in 105 Austrian institutionalised women and men (65-98 years). DNA damage was detected by performing the single cell gel electrophoresis (comet) assay. Physical fitness was assessed using the chair rise, the 6-min-walking and the handgrip strength test. In addition, antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were analysed. Basal DNA damage (lysis) increased significantly after 3 months of intervention in the RT group (T1 - T2 + 20%, P = 0.001) and the RTS group (T1 - T2 + 17%, P = 0.002) and showed a similar tendency in the CT group (T1 - T2 + 21%, P = 0.059). %DNA in tail decreased in cells exposed to H2O2 significantly in the RT (T1 - T2 - 24%, P = 0.030; T1 - T3 - 18%, P = 0.019) and CT (T1 - T2 - 21%, P = 0.004; T1 - T3 - 13%, P = 0.038) groups. Only RT and RTS groups showed significant differences overtime in enzyme activity (RT + 22% CAT-activity T1 - T3, P = 0.013; RTS + 6% SOD-activity T2 - T3, P = 0.005). Contrary to the time effects, no difference between groups was detected for any parameter at any time point. Our results suggest that both CT and RT improve resistance against H2O2 induced DNA damage and that a nutritional supplement has no further protective effect in institutionalised elderly.

Rat liver cells express the multispecific organic anion transporter (cmoat, cmrp, mrp2) and P-glycoprotein (Pgp) in their canalicular membranes, proteins that are homologous to the multidrug-resistance related protein (MRP) and multidrug resistance (MDR) gene products in multidrug resistant tumor cells. We tested whether genistein, a modulator of drug resistance in tumor cells, affects biliary secretion of substrates of canalicular multispecific organic anion transporter (cmoat) (glucuronides of bilirubin and rhodamine, glutathione conjugate of bromsulphthalein) and of P-glycoprotein (Pgp) (rhodamine), respectively. Using the isolated perfused rat liver of control Wistar rats (TR+) and of a mutant strain (TR-) that expresses Pgp but not cmoat, we show that genistein effectively inhibits the secretion of anionic substrates of cmoat in Wistar rats but stimulates secretion of cationic rhodamine in TR- rats. Genistein is subject to glucuronidation and sulfatation and secretion of genistein and its metabolites stimulates bile flow in Wistar rats, but secretion is nearly absent in TR- rats. Because genistein and its metabolites are substrates for cmoat, inhibition of anion secretion by genistein is partially explained by competition for this transporter. Genistein is also a substrate of uridindiphosphate (UDP)-glucuronyltransferase isoenzyme(s). Inhibition of glucuronidation reduces the availability of bilirubin and rhodamine glucuronates for transport via cmoat, but unconjugated cationic rhodamine becomes available for transport via Pgp at an increased cellular concentration. Daidzein, a genistein analogue with no effect on protein tyrosine kinase (PTK) shows Similar effects on secretion of organic anions and cations supporting the conclusion that genistein affects transport in liver mainly through competition with other substrates at the sites of glucuronidation and transport via cmoat.