It has been suggested that reactive oxygen species (ROS) are involved in the generation of altered proteins that are reported to increase with advancing age. Among chemical modifications of proteins, carbonyls are their useful markers that can be determined and characterized by the spectroscopic and immunological analyses of protein samples derivatized with the carbonyl reagent 2,4-dinitrophenylhydrazine. The age-associated accumulation of altered proteins can be caused not only by the age- related increase in ROS generation, but also by the decline of protein degradation. In fact, half-lives of proteins including oxidatively modified proteins in cells from old mice were shown to be significantly longer than those in cells from young mice. A decrease in proteasome activity appears to be primarily responsible for an age-related decline in the degradation of oxidatively modified proteins. Importantly, proteasome itself was suggested to alter with age by its decreased specific activity (the activity per intensity of immunological signals for the subunits), thus likely contributing to form a vicious cycle of accumulation of altered proteins.
Alterations in the oxidative stress resistance of human embryonic lung fibroblasts during aging in vitro and human skin fibroblasts during aging in vivo were examined. Human embryonic lung fibroblasts were serially cultivated, and early- and late-passage cells were used as young and old cells in vitro, respectively. On the other hand, human skin fibroblasts were obtained from young and old donors, and young and old donor’s cells were used as young and old cells in vivo, respectively. Resistance of late-passage cells to oxidative stress caused by hydrogen peroxide, linoleic acid hydroperoxide, or a hypoxanthine-xanthine oxidase system decreases as compared with early-passage cells. Reduced glutathione concentration and catalase activity are lower in late-passage cells than in early-passage cells. The in vitro life span of human embryonic lung fibroblasts is perturbed by oxidative stress. The life span extends and shortens depending on an increase and decrease, respectively, in cellular reduced glutathione concentration. In addition, it shortens by treatment of either hyperbaric oxygen or the catalase inhibitor 3-amino-1H-1,2,4-triazole. On the other hand, resistance of old donor’s skin fibroblasts to oxidative stress caused by hydrogen peroxide, linoleic acid hydroperoxide, or ultraviolet light B is enhanced as compared with young donor’s fibroblasts. Glutathione peroxidase activity is much higher in old donor’s cells than in young donor’s cells. These results suggest that human fibroblasts become resistant to oxidative stress during aging in vivo, while they become vulnerable during aging in vitro, and that their primary defense against oxidative stress appears to be the reduced glutathione-glutathione peroxidase system.
Serum nutritional components and food intake were examined in Nepalese (127 males and 163 females aged 4 to 72 years) living in a remote hilly village (area A and B, area A is located at a relatively lower altitude and is warmer) in the eastern region of Nepal. Mean values of height and weight for the groups covering ages 4 to 19 of both sexes and in both areas increased with age. The mean BMI value for each age group was mostly under 22, and the BMI correlated with age, and with systolic and diastolic blood pressure. The mean values of serum components were about the same levels in both sexes. Mean values of triglyceride (TG) of over 150 mg/dl were found in males 20–50 years old and in females over 50 years old in area A, and generally the mean values of TG of the subjects tended to be in the higher range of normal. The main foods consumed in both areas were rice, maize, potatoes, pulses, milk and dairy products, and vegetables, with a difference in the amounts consumed. Milk and dairy products were almost the sole food source of animal origin. The rather higher serum TG levels of the subjects may be due to large amounts of consumption of cereals containing a lot of carbohydrate, which transformed into lipids in the metabolic pathway. The present food intake study revealed that the amounts of food consumed were not adequate resulting in a latent and chronic deficiency of nutrients, especially such as calcium (Ca), iron (Fe), and fat-soluble vitamins. These results suggest that improvement of the nutritional status is needed in this people group.