Hypothalamic circuits and aging: keeping the circadian clock updated

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(9), P. 1919 - 1928

Published: Dec. 14, 2023

Over the past century, age-related diseases, such as cancer, type-2 diabetes, obesity, and mental illness, have shown a significant increase, negatively impacting overall quality of life. Studies on aged animal models unveiled progressive discoordination at multiple regulatory levels, including transcriptional, translational, post-translational processes, resulting from cellular stress circadian derangements. The clock emerges key regulator, sustaining physiological homeostasis promoting healthy aging through timely molecular coordination pivotal stem-cell function, responses, inter-tissue communication, which become disrupted during aging. Given crucial role hypothalamic circuits in regulating organismal physiology, metabolic control, sleep homeostasis, rhythms, their dependence these strategies aimed enhancing pharmacological non-pharmacological approaches, offer systemic benefits for Intranasal brain-directed drug administration represents promising avenue effectively targeting specific brain regions, like hypothalamus, while reducing side effects associated with delivery, thereby presenting new therapeutic possibilities diverse conditions.

Language: Английский

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β‐Carotene Impacts the Liver microRNA Profile in a Sex‐Specific Manner in Mouse Offspring of Western Diet‐Fed Mothers: Results from Microarray Analysis by Direct Hybridization

Published: April 25, 2024

Maternal unbalanced diets cause adverse metabolic programming and affect the offspring's liver microRNA profile. The is a site of β-carotene (BC) metabolism target BC action. We studied interaction maternal Western diet (WD) early-life supplementation on epigenetic remodeling offspring’s microRNAs. Mouse offspring WD-fed mothers were given daily placebo (controls) or during suckling. miRNAome was analyzed in recently weaned animals by microarray hybridization. impacted differently male female offspring, with no overlap differentially expressed (DE) miRNAs between sexes more impact females. Bioinformatic analysis DE miRNA predicted genes revealed enrichment biological processes/pathways related to processes, regulation developmental growth circadian rhythm, homeostasis metabolism, insulin resistance, neurodegeneration, among others, differences sexes. Fifty five percent overlapping both identified targeted changed opposite directions males results identify sex-dependent responses expression profile suckling may sustain further investigations regarding long-term early postnatal life top an diet.

Language: Английский

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Short‐term exercise counteracts accelerated ageing impacts on physical performance and liver health in mice

Clinical and Experimental Pharmacology and Physiology, Journal Year: 2024, Volume and Issue: 51(12)

Published: Oct. 30, 2024

Senescence impairs liver physiology, mitochondrial function and circadian regulation, resulting in systemic metabolic dysregulation. Given the limited research on effects of combined exercise an ageing liver, this study aimed to evaluate its impact metabolism, rhythms senescence-accelerated mouse-prone 8 (SAMP8) mouse-resistant 1 (SAMR1) mice. Histological, reverse transcription quantitative polymerase chain reaction (RT-qPCR) immunoblotting analyses were conducted, supplemented by transcriptomic data sets AML12 hepatocyte studies. Sedentary SAMP8 mice exhibited decreased muscle strength, reduced complex I levels increased lipid droplet accumulation. In contrast, mitigated strength loss, upregulated proteins involved complexes (CIII, CIV, CV) Bmal1 messenger RNA (mRNA) expression liver. These molecular adaptations are associated with healthier phenotypes may influence cellular longevity. Notably, elevated content aged was post-exercise, indicating benefits even after a relatively short intervention. The regimen did not improve aerobic capacity, likely due low volume brief duration running. Moreover, no significant observed SAMR1 mice, possibly because training intensity insufficient for younger, animals. findings underscore potential endurance attenuate age-related dysfunction, particularly populations.

Language: Английский

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Impact of Long-Term Cannabidiol (CBD) Treatment on Mouse Kidney Transcriptome

Genes, Journal Year: 2024, Volume and Issue: 15(12), P. 1640 - 1640

Published: Dec. 21, 2024

Background: Cannabidiol, which is one of the main cannabinoids present in Cannabis sativa plants, has been shown to have therapeutic properties, including anti-inflammatory and antioxidant effects that may be useful for treatment various kidney conditions. Objectives: This article investigates effect long-term cannabidiol (CBD) on changes renal transcriptome a mouse model. The hypothesis was systematic CBD would affect gene expression associated with those processes kidney. Methods: study conducted male C57BL/6J mice. Mice experimental groups received daily intraperitoneal injections at doses 10 mg/kg or 20 body weight (b.w.) 28 days. After experiment, tissues were collected, RNA isolated, RNA-Seq sequencing performed. Results: results show CBD’s expression, regulation genes related circadian rhythm (e.g., Ciart, Nr1d1, Nr1d2, Per2, Per3), glucocorticoid receptor function Cyp1b1, Ddit4, Foxo3, Gjb2, Pck1), lipid metabolism Cyp2d22, Cyp2d9, Decr2 Hacl1, Sphk1), inflammatory response Cxcr4 Ccl28). Conclusions: obtained suggest beneficial purposes treating disease, its should further analyzed clinical trials.

Language: Английский

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