MicroRNA miR-128 represses LINE-1 (L1) retrotransposition by down-regulating the nuclear import factor TNPO1.

Repetitive elements, including LINE-1 (L1), comprise approximately half of the human genome. These elements can potentially destabilize the genome by initiating their own replication and reintegration into new sites (retrotransposition). In somatic cells, transcription of L1 elements is repressed by distinct molecular mechanisms, including DNA methylation and histone modifications, to repress transcription. Under conditions of hypomethylation (e.g. in tumor cells), a window of opportunity for L1 derepression arises, and additional restriction mechanisms become crucial. We recently demonstrated that the microRNA miR-128 represses L1 activity by directly binding to L1 ORF2 RNA. In this study, we tested whether miR-128 can also control L1 activity by repressing cellular proteins important for L1 retrotransposition. We found that miR-128 targets the 3' UTR of nuclear import factor transportin 1 (TNPO1) mRNA. Manipulation of miR-128 and TNPO1 levels demonstrated that induction or depletion of TNPO1 affects L1 retrotransposition and nuclear import of an L1-ribonucleoprotein complex (using L1-encoded ORF1p as a proxy for L1-ribonucleoprotein complexes). Moreover, TNPO1 overexpression partially reversed the repressive effect of miR-128 on L1 retrotransposition. Our study represents the first description of a protein factor involved in nuclear import of the L1 element and demonstrates that miR-128 controls L1 activity in somatic cells through two independent mechanisms: direct binding to L1 RNA and regulation of a cellular factor necessary for L1 nuclear import and retrotransposition

The impact of Rhodiola rosea on the gut microbial community of Drosophila melanogaster.

BackgroundThe root extract of Rhodiola rosea has historically been used in Europe and Asia as an adaptogen, and similar to ginseng and Shisandra, shown to display numerous health benefits in humans, such as decreasing fatigue and anxiety while improving mood, memory, and stamina. A similar extract in the Rhodiola family, Rhodiola crenulata, has previously been shown to confer positive effects on the gut homeostasis of the fruit fly, Drosophila melanogaster. Although, R. rosea has been shown to extend lifespan of many organisms such as fruit flies, worms and yeast, its anti-aging mechanism remains uncertain. Using D. melanogaster as our model system, the purpose of this work was to examine whether the anti-aging properties of R. rosea are due to its impact on the microbial composition of the fly gut.ResultsRhodiola rosea treatment significantly increased the abundance of Acetobacter, while subsequently decreasing the abundance of Lactobacillales of the fly gut at 10 and 40 days of age. Additionally, supplementation of the extract decreased the total culturable bacterial load of the fly gut, while increasing the overall quantifiable bacterial load. The extract did not display any antimicrobial activity when disk diffusion tests were performed on bacteria belonging to Microbacterium, Bacillus, and Lactococcus.ConclusionsUnder standard and conventional rearing conditions, supplementation of R. rosea significantly alters the microbial community of the fly gut, but without any general antibacterial activity. Further studies should investigate whether R. rosea impacts the gut immunity across multiple animal models and ages

Cinnamaldehyde Improves Lifespan and Healthspan in Drosophila melanogaster Models for Alzheimer's Disease.

Cinnamon extract has been reported to have positive effects in fruit fly and mouse models for Alzheimer's disease (AD). However, cinnamon contains numerous potential active compounds that have not been individually evaluated. The main objective of this study was to evaluate the impact of cinnamaldehyde, a known putative active compound in cinnamon, on the lifespan and healthspan of Drosophila melanogaster models for Alzheimer's disease, which overexpress Aβ42 and MAPT (Tau). We found that cinnamaldehyde significantly improved the lifespan of both AD and non-AD flies. Cinnamaldehyde also improved the healthspan of AD flies overexpressing the Tau protein by improving climbing ability, evaluated by rapid iterative negative geotaxis (RING), and improving short-term memory, evaluated by a courtship conditioning assay. Cinnamaldehyde had no positive impact on the healthspan of AD flies overexpressing the Aβ42 protein

Cinnamaldehyde Improves Lifespan and Healthspan in Drosophila melanogaster Models for Alzheimer’s Disease

Cinnamon extract has been reported to have positive effects in fruit fly and mouse models for Alzheimer’s disease (AD). However, cinnamon contains numerous potential active compounds that have not been individually evaluated. The main objective of this study was to evaluate the impact of cinnamaldehyde, a known putative active compound in cinnamon, on the lifespan and healthspan of Drosophila melanogaster models for Alzheimer’s disease, which overexpress Aβ42 and MAPT (Tau). We found that cinnamaldehyde significantly improved the lifespan of both AD and non-AD flies. Cinnamaldehyde also improved the healthspan of AD flies overexpressing the Tau protein by improving climbing ability, evaluated by rapid iterative negative geotaxis (RING), and improving short-term memory, evaluated by a courtship conditioning assay. Cinnamaldehyde had no positive impact on the healthspan of AD flies overexpressing the Aβ42 protein

Rhodiola rosea Improves Lifespan, Locomotion, and Neurodegeneration in a Drosophila melanogaster Model of Huntington's Disease.

Huntington's disease (HD) is a dominant, late-onset disease characterized by choreiform movements, cognitive decline, and personality disturbance. It is caused by a polyglutamine repeat expansion in the Huntington's disease gene encoding for the Huntingtin protein (Htt) which functions as a scaffold for selective macroautophagy. Mutant Htt (mHtt) disrupts vesicle trafficking and prevents autophagosome fusion with lysosomes, thus deregulating autophagy in neuronal cells, leading to cell death. Autophagy has been described as a therapeutic target for HD, owing to the key role Htt plays in the cellular process. Rhodiola rosea, a plant extract used in traditional medicine in Europe and Asia, has been shown to attenuate aging in the fly and other model species. It has also been shown to inhibit the mTOR pathway and induce autophagy in bladder cancer cell lines. We hypothesized that R. rosea, by inducing autophagy, may improve the phenotype of a Huntington's disease model of the fly. Flies expressing HttQ93 which exhibit decreased lifespan, impaired locomotion, and increased neurodegeneration were supplemented with R. rosea extract, and assays testing lifespan, locomotion, and pseudopupil degeneration provided quantitative measures of improvement. Based on our observations, R. rosea may be further evaluated as a potential therapy for Huntington's disease

Rhodiola rosea Improves Lifespan, Locomotion, and Neurodegeneration in a Drosophila melanogaster Model of Huntington’s Disease

Huntington’s disease (HD) is a dominant, late-onset disease characterized by choreiform movements, cognitive decline, and personality disturbance. It is caused by a polyglutamine repeat expansion in the Huntington’s disease gene encoding for the Huntingtin protein (Htt) which functions as a scaffold for selective macroautophagy. Mutant Htt (mHtt) disrupts vesicle trafficking and prevents autophagosome fusion with lysosomes, thus deregulating autophagy in neuronal cells, leading to cell death. Autophagy has been described as a therapeutic target for HD, owing to the key role Htt plays in the cellular process. Rhodiola rosea, a plant extract used in traditional medicine in Europe and Asia, has been shown to attenuate aging in the fly and other model species. It has also been shown to inhibit the mTOR pathway and induce autophagy in bladder cancer cell lines. We hypothesized that R. rosea, by inducing autophagy, may improve the phenotype of a Huntington’s disease model of the fly. Flies expressing HttQ93 which exhibit decreased lifespan, impaired locomotion, and increased neurodegeneration were supplemented with R. rosea extract, and assays testing lifespan, locomotion, and pseudopupil degeneration provided quantitative measures of improvement. Based on our observations, R. rosea may be further evaluated as a potential therapy for Huntington’s disease

The impact of Rhodiola rosea on the gut microbial community of Drosophila melanogaster

Abstract Background The root extract of Rhodiola rosea has historically been used in Europe and Asia as an adaptogen, and similar to ginseng and Shisandra, shown to display numerous health benefits in humans, such as decreasing fatigue and anxiety while improving mood, memory, and stamina. A similar extract in the Rhodiola family, Rhodiola crenulata, has previously been shown to confer positive effects on the gut homeostasis of the fruit fly, Drosophila melanogaster. Although, R. rosea has been shown to extend lifespan of many organisms such as fruit flies, worms and yeast, its anti-aging mechanism remains uncertain. Using D. melanogaster as our model system, the purpose of this work was to examine whether the anti-aging properties of R. rosea are due to its impact on the microbial composition of the fly gut. Results Rhodiola rosea treatment significantly increased the abundance of Acetobacter, while subsequently decreasing the abundance of Lactobacillales of the fly gut at 10 and 40 days of age. Additionally, supplementation of the extract decreased the total culturable bacterial load of the fly gut, while increasing the overall quantifiable bacterial load. The extract did not display any antimicrobial activity when disk diffusion tests were performed on bacteria belonging to Microbacterium, Bacillus, and Lactococcus. Conclusions Under standard and conventional rearing conditions, supplementation of R. rosea significantly alters the microbial community of the fly gut, but without any general antibacterial activity. Further studies should investigate whether R. rosea impacts the gut immunity across multiple animal models and ages