No abstract

Chemical reagent Ex-527 is widely used as a major inhibitor of Sirtuin enzymes, which are a family of highly conserved protein deacetylases and have been linked with caloric restriction and aging by modulating energy metabolism, genomic stability, and stress resistance. However, the extent to which Ex-527 controls early developmental events of vertebrate embryos remains to be understood. Here, we report an examination of Ex-527 effects during Xenopus early development, followed by a confirmation of expressions of xSirt1 and xSirt2 in embryonic stages and enhancement of acetylation by Ex-527. First, we found that reductions in size of neural plate at neurula stages were induced by Ex-527 treatment. Second, tadpoles with short body length and large edematous swellings in the ventral side were frequently observed. Moreover, Ex-527-treated embryos showed severe gastrointestinal malformations in late tadpole stages. Taken together with these results, we conclude that the Sirtuin family start functioning at early embryonic stages and is required for various developmental events.

Calorie restriction (CR) by 30-40% decreases morbidity of age-related diseases and prolongs the lifespan of various laboratory animal species. Taurine (2-aminoethanesulfonic acid) is an important nutrient for lipid metabolism as it conjugates bile acids. Here, we investigated how taurine supplementation induces effects similar to the CR beneficial effects. Sprague Dawley rats were fed a diet containing different taurine concentrations (0, 0.5, 1.0, 3.0, 5.0%) to analyze the effects on growth, blood, and hepatic parameters. Rats fed a 5% taurine-supplemented diet showed a significant decrease in visceral fat weight, compared with control rats. Moreover, there were significant decreases in the serum total cholesterol, hepatic cholesterol and triglyceride concentrations in the taurine-supplemented groups compared with the control group in a dose-dependent manner. These results were associated with decreased mRNA expression of fatty acid synthase, and increased mRNA expression of carnitine palmitoyltransferase 1a. C57BL/6 mice were fed a 5.0% taurinesupplemented diet, and their response to 3-nitropropionic acid-induced oxidative stress was analyzed. The rate of weight loss due to oxidative stress decreased and the survival rate significantly increased in the taurine-supplemented groups compared with the control group. Finally, cells were treated with 100 mm taurine and their resistance to UV-induced oxidative stress was analyzed. We found that the p53-Chk1 pathway was less activated in taurine-treated cells compared with control cells. Furthermore, damage to cells evaluated by oxidative stress indicators revealed a reduction in oxidative damage with taurine treatment. These findings suggest that taurine partially acts as a CR mimetic.

Aim Caloric restriction (CR), which limits the caloric intake to 60–70% of ad libitum (AL) amounts in various experimental animals, delays aging and extends the lifespan. We previously showed that neuropeptide Y (NPY), an appetite‐stimulating peptide, is essential for the anti‐oxidative and life‐extending effects of CR. Here, we investigated whether a Japanese traditional herbal medicine, rikkunshito (RKT), which induces NPY activation, has CR‐like life‐extending effects. Methods First, we evaluated the life‐extending activity of RKT by examining the effect of long‐term RKT administration on wild‐type and NPY knockout mice. Furthermore, we tested whether RKT enhances CR‐mediated beneficial effects under AL conditions with a normal diet and under mild CR conditions with a high‐fat diet. We then used 3‐nitropropionic acid or doxorubicin to induce oxidative stress, and analyzed the differences in survival rate, weight loss, gene expression and cellular oxidative damage among groups. Results RKT administration did not extend the lifespan of wild‐type or NPY knockout mice. In the oxidative stress models, RKT treatment upregulated anti‐oxidative gene expression in the liver. Furthermore, RKT administration reduced the oxidative damage in the liver compared to the CR conditions alone. However, on induction of oxidative stress by 3‐nitropropionic acid or doxorubicin, RKT administration did not affect the survival rate. Conclusions These results show that RKT administration only partially mimics the effects of CR at the cellular level, but not at the organismal level to increase the lifespan of mice. Geriatr Gerontol Int 2019; ••: ••–••.

More than 80 years ago, McCay and colleagues first reported that limiting the amount of food provided to experimental animals (i.e. calorie restriction or CR) prolongs their lifespan and suppresses the onset and progression of various age-related diseases. Today, CR remains the most reliable method of delaying aging in experimental animals, and research into its underlying molecular mechanisms is ongoing. CR has been reported to have anti-aging and life-extension effects on primates, with progress being made toward applications for humans. Studies on mechanisms underlying the onset and prevention of lifestyle-related diseases such as diabetes have elucidated the cellular signaling pathways that regulate energy metabolism, and commonalities have been discovered between the targets of existing diabetes drugs and the signaling pathways affected by CR. This finding has led to research into the discovery of drugs that have the anti-aging effects of CR in the absence of food intake limitations, namely CR mimetics (CRM). Several drugs have been reported to extend the lifespan of experimental organisms, which may thus have the potential to also extend human lifespan. In this article, we outline and compare those drugs that have been reported to date and discuss the possibility of taurine as a CRM, which is a topic of our ongoing research.