Short report Expression of mRNA for ROS-generating NADPH oxidases in the aging stomach Nathalie Salles a, * , Ildiko Szanto a , Franc ¸ois Herrmann a , Berge Armenian a , Michael Stumm b , Edouard Stauffer c , Jean-Pierre Michel a , Karl-Heinz Krause a a Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland b Department of Research, Basel University Hospital, Basel, Switzerland c Department of Pathology, Berne University Hospital, Berne, Switzerland Received 17 December 2003; received in revised form 7 January 2005; accepted 13 January 2005 Available online 10 February 2005 Abstract Oxidative damage is thought to play a key role in the aging of various organ systems. In this study, we have therefore analyzed mRNA expression of ROS-generating NADPH oxidases in the aging stomach. Gastric biopsies of hospitalized geriatric patients were analyzed for histology (Sidney classification), and real-time PCR was used to quantify mRNA expression of the superoxide-generating NADPH oxidases NOX1, NOX2, and NOX5. We found that stomach biopsies of elderly patients expressed NOX5 and NOX2 mRNA, but not NOX1. The mRNA expression of NOX5 (a lymphocyte NADPH oxidase) neither depended on age nor on the results of the stomach histology. In contrast, mRNA expression of NOX2 (phagocyte NADPH oxidase) was a function of two variables. Increased NOX2 mRNA levels were observed in biopsies with signs of chronic inflammation (pZ0.01). Interestingly, however, there was also an age-dependent increase in NOX2 mRNA levels (pZ0.01). We conclude that in elderly patients the gastric mRNA expression of the ROS-generating enzyme NOX2 increases as a function of age, possibly contributing to stomach aging and gastric vulnerability of the elderly. q 2005 Elsevier Inc. All rights reserved. Keywords: ROS-generating NADPH oxidase; Real-time PCR; mRNA 1. Introduction There is increasing evidence that reactive oxygen species (ROS), play a key role in tissue damage and aging (Beckman and Ames, 1998). ROS seem to exert such function through diverse mechanisms including non-selective damage of various molecules, induction of programmed cell death, but also through activation of redox-sensitive transcription factors and signaling molecules (Finkel, 2000). The molecu- lar sources of ROS that contribute to the aging process are still a matter of debate. ROS generation by mitochondria has been consistently implied (Lenaz et al., 2002), but more recently the role of the NOX family of superoxide-generating NADPH oxidases (Lambeth, 2002; Zekry et al., 2003) is receiving increased attention. NADPH oxidases expressed in the vascular system (NOX1, NOX2, and NOX4) appear to be involved in vascular aging (Cai et al., 2003), and NOX2 might play a role in age-associated loss of neurons (Zekry et al., 2003). NOX4 expression has been shown to directly induce cellular senescence (Geiszt et al., 2000). Little is known about NADPH oxidase expression in the stomach and its relationship with the aging process. Expression of NOX1 in gastric pit cells of guinea pig has been suggested (Teshima et al., 2000), but Northern blot analysis of human stomach did not show NOX1 expression (Banfi et al., 2000). It was the aim of this study to investigate mRNA expression of NOX in human gastric biopsies from elderly patients. 2. Methods 2.1. Clinical samples Patients (i) older than 75, (ii) hospitalized in the Department of Rehabilitation and Geriatrics, and (iii) having 0531-5565/$ - see front matter q 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.exger.2005.01.007 Experimental Gerontology 40 (2005) 353–357 www.elsevier.com/locate/expgero * Corresponding author. Address: De ´partement de Ge ´riatrie, Centre Hospitalo-Universitaire de Bordeaux, Ho ˆpital Xavier Arnozan, 33604 Pessac, France. Tel.: C33 557 656 610; fax: C33 557 656 224. E-mail address: nathalie.salles@chu-bordeaux.fr (N. Salles).