Epigenetic changes may be causal in the ageing process and may be influenced by diet, providing opportunities to improve health in later life. The aim of this review is to provide an overview of several areas of research relevant to this topic and to explore a hypothesis relating to a possible role of epigenetic effects, mediated by sirtuin 1, in the beneficial effects of dietary restriction, including increased lifespan. Epigenetic features of ageing include changes in DNA methylation, both globally and at specific loci, which differ between individuals. A major focus of research on dietary influences on epigenetic status has been on nutrition in utero, because the epigenome is probably particularly malleable during this life-course window and because epigenetic marking by early exposures is a compelling mechanism underlying effects on lifelong health. We explore the potential of diet during adulthood, including the practice of dietary restriction, to affect the epigenetic architecture. We report progress with respect to deriving data to support our hypothesis that sirtuin 1 may mediate some of the effects of dietary restriction through effects on DNA methylation and note observations that resveratrol affects DNA methylation and other epigenetic features. Disentangling cause and effect in the context of epigenetic change and ageing is a challenge and requires better understanding of the underlying mechanisms and also the development of more refined experimental tools to manipulate the epigenetic architecture, to facilitate hypothesis-driven research to elucidate these links and thus to exploit them to improve health across the full life-course through dietary measures.
BackgroundIn diabetes mellitus, uncontrolled hyperglycemia has been reported to induce oxidative stress, which may lead to health complications. Vitamin D, however, acts as a non-enzymatic antioxidant to protect cells against oxidative stress and damage.ObjectiveTo investigate the antioxidative effect of vitamin D combined with calcium in streptozotocin (STZ)-induced diabetic rats.MethodsRats were divided into four groups (ten rats in each group). The first group (control) received a normal diet and water. The second group, including STZ-induced diabetic rats (diabetic controls), received a normal diet and water. The third group, also including STZ-induced diabetic rats, received vitamin D (2000 IU/day) with calcium (500 mg/kg/day) orally for 28 consecutive days. The fourth group consisted of STZ-induced diabetic rats that received insulin treatment for 28 consecutive days. Activities of superoxide dismutase (SOD), glutathione peroxidase (GPO) and catalase were measured in the liver tissues. The level of malonaldehyde (MDA) was measured in the plasma.ResultsDiabetic rats showed a significant decrease in the activities of SOD, GPO and catalase compared to normal rats. Oral administration of vitamin D with calcium to diabetic rats caused a significant increase in the activities of SOD, GPO and catalase compared with the untreated group. Furthermore, the plasma level of MDA was significantly elevated in diabetic rats compared to normal rats. Diabetic rats treated with vitamin D and calcium had a significantly reduced level of MDA, suggesting that vitamin D with calcium played a vital role in the protection of tissues from damage by free radicals.ConclusionOral supplementation with vitamin D and calcium may be a useful treatment for diabetic patients to reduce/prevent the pathological complications of diabetes.
Alzheimer’s disease is a major public brain condition that has resulted in many deaths, as revealed by the World Health Organization (WHO). Conventional Alzheimer’s treatments such as chemotherapy, surgery, and radiotherapy are not very effective and are usually associated with several adverse effects. Therefore, it is necessary to find a new therapeutic approach that completely treats Alzheimer’s disease without many side effects. In this research project, we report the synthesis and biological activities of some new thiazole-bearing sulfonamide analogs (1–21) as potent anti-Alzheimer’s agents. Suitable characterization techniques were employed, and the density functional theory (DFT) computational approach, as well as in-silico molecular modeling, has been employed to assess the electronic properties and anti-Alzheimer’s potency of the analogs. All analogs exhibited a varied degree of inhibitory potential, but analog 1 was found to have excellent potency (IC50 = 0.10 ± 0.05µM for AChE) and (IC50 = 0.20 ± 0.050 µM for BuChE) as compared to the reference drug donepezil (IC50 = 2.16 ± 0.12 µM and 4.5 ± 0.11 µM). The structure-activity relationship was established, and it mainly depends upon the nature, position, number, and electron-donating/-withdrawing effects of the substituent/s on the phenyl rings.
Triazole-based thiosemicarbazone derivatives (6a–u) were synthesized then characterized by spectroscopic techniques, such as 1HNMR and 13CNMR and HRMS (ESI). Newly synthesized derivatives were screened in vitro for inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All derivatives (except 6c and 6d, which were found to be completely inactive) demonstrated moderate to good inhibitory effects ranging from 0.10 ± 0.050 to 12.20 ± 0.30 µM (for AChE) and 0.20 ± 0.10 to 14.10 ± 0.40 µM (for BuChE). The analogue 6i (IC50 = 0.10 ± 0.050 for AChE and IC50 = 0.20 ± 0.050 µM for BuChE), which had di-substitutions (2-nitro, 3-hydroxy groups) at ring B and tri-substitutions (2-nitro, 4,5-dichloro groups) at ring C, and analogue 6b (IC50 = 0.20 ± 0.10 µM for AChE and IC50 = 0.30 ± 0.10 µM for BuChE), which had di-Cl at 4,5, -NO2 groups at 2-position of phenyl ring B and hydroxy group at ortho-position of phenyl ring C, emerged as the most potent inhibitors of both targeted enzymes (AChE and BuChE) among the current series. A structure–activity relationship (SAR) was developed based on nature, position, number, electron donating/withdrawing effects of substitution/s on phenyl rings. Molecular docking studies were used to describe binding interactions of the most active inhibitors with active sites of AChE and BuChE.
Dietary restriction (DR) increases lifespan robustly in diverse species (1) . Effects of the dietary polyphenol resveratrol consistent with delayed ageing and/or extension of lifespan have been reported (1) . The protein Sirt1 is involved in the longevity response to DR and can be activated by resveratrol. Sirt1 deacetylates a range of cellular substrates that includes histone proteins (1) , identifying epigenetic processes as a pathway that may mediate the effects of both DR and dietary resveratrol in delaying ageing and/or extending lifespan.We investigated the hypothesis that resveratrol brings about histone deacetylation to oppose changes in histone modification that accompany ageing. A secondary hypothesis, based on a degree of structural similarity between resveratrol and 17 b-oestradiol, is that epigenetic effects of resveratrol are mediated through the oestrogen receptor (ER).Human intestinal Caco-2 cells or human MCF-7 breast cancer cells were treated with resveratrol (10 mM) for 72 h in the presence or absence of the ER antagonist fulvestrant (0.1 mM), then semi-purified histone proteins or total cell lysate were analysed by western blotting using an antibody specific for histone 4 (H4) acetylated at Lys16 or using antibodies immunoreactive against H4 or H3 irrespective of acetylation status. Where total cell lysate was analysed, blots were probed with an antibody immunoreactive against a-tubulin to correct for protein loading/transfer. Where histone proteins were extracted before analysis, equal loading was confirmed by staining a duplicate gel with Coomassie Brilliant Blue. Quantitative data were derived by densitometric quantification of band intensities and are expressed as mean (SEM) normalised to control.Both anti-H4 antibodies revealed a marked reduction in the H4 signal after the treatment of Caco-2 cells with resveratrol (0.13 (0.06), P < 0.01, n 3 for H4-Lys16, and 0.25 (0.13), P < 0.05, n 3 for total H4 protein; both based on analysis of total extracted histone protein), indicating that resveratrol treatment reduces H4 protein expression, rather than affecting acetylation status. Similarly, the intensity of the immunoreactive band detected using the anti-H3 antibody was reduced by treatment of MCF-7 cells with resveratrol (0.67 (0.13), P < 0.05, n 3, based on the analysis of total cell protein and corrected based on the signal for a-tubulin). This effect of resveratrol was attenuated by the ER antagonist fulvestrant (1.06 (0.03), n 3), indicating that resveratrol reduced histone H3 expression via an ER-dependent mechanism. Preliminary data also reveal attenuation by fulvestrant of the reduction in H4 observed in Caco-2 cells in response to resveratrol.In support of our hypothesis that resveratrol affects ageing through reversing ageing-associated changes in histone proteins, higher levels (P < 0.05) of H4 expression were detected by western blotting in the small intestine of old (38 months) C57Bl6 mice (8.01 (2.88), n 3) than in younger (12 months) mice (1.00 (0.62), n 3). Similar changes...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.