Protecting against oxidative damage and improving healthspan

Protecting against oxidative damage and improving healthspan
 


Researchers have tried to increase the global antioxidant capacity of the cells, rather than just one or a few antioxidant enzymes. To achieve this global improvement in the total antioxidant capacity, researches have focused on increasing the levels of NADPH, a relatively simple molecule that is of key importance in antioxidant reactions and that, however, had not been studied to date in relation to ageing.

The researchers used a genetic approach to increase NADPH levels. In particular, they generated transgenic mice with an increased expression throughout their bodies of one of the most important enzymes for the production of NADPH, namely, glucose-6-phosphate dehydrogenase (or G6PD).

The results, published today in the journal Nature Communications, indicate that an increase in G6PD and, therefore, in NADPH, increases the natural antioxidant defences of the organism, protecting it from oxidative damage, reducing ageing-related processes, such as insulin resistance, and increasing longevity.

Furthermore, when researchers analysed long-lived transgenic animals, they noted that their levels of oxidative damage were lower than in non-transgenic animals of the same age. They also studied the propensity of these animals to develop cancer and found no difference, suggesting that enhancing G6PD activity does not have an important effect on the development of cancer.

The greatest surprise for the team was when they measured the ageing process in the transgenic mice: the animals with a high G6PD expression and, therefore, high levels of NADPH, delayed their ageing, metabolised sugar better and presented better movement coordination as they aged. In addition, transgenic females lived 14% longer than non-transgenic mice, while no significant effect on the longevity of males was observed.

Perhaps the key is that the researchers involved in this paper enhanced all antioxidant enzymes in a comprehensive manner. "Compared to the traditional approach of administering antioxidants that react directly with oxygen, we have stimulated all the cell's natural antioxidant mechanisms by raising G6PD levels, and its by-product, NADPH," said the author.

Based on these results, the authors of the study point to the use of pharmacological agents or nutritional supplements that increase NADPH levels as potential tools for delaying the ageing process in humans and age-related diseases, such as diabetes, among others. More specifically, vitamin B3 and its derivatives are responsible for the synthesis of NADPH precursors and are suitable candidates for future studies.

http://www.cnio.es/ing/publicaciones/a-global-increase-in-antioxidant-defences-of-the-body-may-delay-ageing-and-its-diseases
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