Impaired response to oxidative stress in senescent cells may lead to accumulation of DNA damage in mesothelial cells from aged donors

Abstract

The accumulation of 8-hydroxy-2′-deoxyguanosine (8-OH-dG) exemplifies oxidative DNA injury, which is strongly implicated in ageing. We show that human peritoneal mesothelial cells (HPMCs) from donors >75 years have lower proliferative capacity but increased 8-OH-dG content compared with cells from individuals <25 years. We detected a positive relationship between the donor’s age and the 8-OH-dG level in early-passage HPMCs, and an inverse relationship between those 8-OH-dG levels and subsequent replicative lifespan of HPMCs ( n = 30). In early-passage cells from donors >75 years, the repair of oxidant-induced 8-OH-dG was delayed compared to cells from donors <25 years. This was coupled with prolonged removal of reactive oxygen species and faster decline in superoxide dismutase activity. Similar effects were observed in HPMCs rendered senescent in vitro. These results indicate that increased 8-OH-dG levels in HPMCs from aged individuals may reflect the in vivo presence of senescent cells with increased vulnerability to oxidative stress-induced DNA damage.