Reduced pulmonary function is age-dependent in the rat lung in normoxia

BACKGROUND: Oxygen transport is optimized at the cellular level, since oxygen serves as the terminal electron acceptor in mitochondrial oxidative phosphorylation and several enzymatic processes require molecular oxygen as substrate. During development and aging, redundant cells and exhausted cells are eliminated, respectively, whereas others can adapt to the stressful environment and survive. OBJECTIVE: The study investigated the molecular mechanisms activated in the lung during normal aging, through the expression of hypoxia inducible factor (HIF), vascular endothelial growth factor (VEGF), p53, p66(Shc), putative cysteine protease (CPP32) and kinaseB-α phosphorylation (pIkB-α). MATERIALS AND METHODS: Twelve male Wistar rats divided into two age-groups, each consisting of 6 animals, 3 and 24 months old, were used. The rats were anesthetized with Nembutal (40 mg/kg, ip) and the lungs were excised from each rat and processed for TUNEL and Western blotting analyses. RESULTS: The expressions of p53, p66(Shc )and CPP32 were significantly increased in the old normoxic rat lung specimens, when compared with the young ones. In parallel, expressions of VEGF and pIkBα were increased in old rather than young rats. CONCLUSIONS: Aging leads to increased expressions of p53, p66(Shc )and CPP32, suggesting that apoptosis is in progress. At the same time, the lung tries to counteract apoptosis through the production of VEGF and pIkB-α to adapt itself to a stressful situation. The aging lung creates a life-support system in order to counteract the apoptotic process.