Regulation of protein O-GlcNAcylation by circadian, metabolic, and cellular signals DOI Creative Commons
Xianhui Liu, Yao D. Cai, Joanna C. Chiu

et al.

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 300(2), P. 105616 - 105616

Published: Dec. 29, 2023

O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a dynamic post-translational modification that regulates thousands of proteins and almost all cellular processes. Aberrant O-GlcNAcylation has been associated with numerous diseases, including cancer, neurodegenerative cardiovascular type 2 diabetes. highly nutrient-sensitive since it dependent on UDP-GlcNAc, the end product hexosamine biosynthetic pathway (HBP). We previously observed daily rhythmicity protein in Drosophila model sensitive to timing food consumption. showed circadian clock pivotal regulating rhythms given its control feeding-fasting cycle hence nutrient availability. Interestingly, we reported also modulates rhythm by molecular mechanisms beyond regulation consumption time. A large body work now indicates likely generalized status effector as responds various signals conditions, such ER stress, apoptosis, infection. In this review, summarize metabolic through availability, HBP enzymes, O-GlcNAc processing enzymes. discuss emerging roles clocks rhythm. Finally, provide an overview other or conditions impact O-GlcNAcylation. Many these pathways are themselves regulated and/or metabolism. Our review highlights importance maintaining optimal restricting eating activity active period under physiological provides insights into potential therapeutic targets homeostasis pathological conditions.

Language: Английский

Molecular mechanisms and physiological importance of circadian rhythms DOI
Alina Patke, Michael W. Young, Sofia Axelrod

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 21(2), P. 67 - 84

Published: Nov. 25, 2019

Language: Английский

Citations

977
Association between circadian rhythms and neurodegenerative diseases DOI
Yue Leng, Erik S. Musiek, Kun Hu

et al.

The Lancet Neurology, Journal Year: 2019, Volume and Issue: 18(3), P. 307 - 318

Published: Feb. 12, 2019

Language: Английский

Citations

509
A systematic approach to quantitative Western blot analysis DOI Creative Commons
Lakshmi Pillai‐Kastoori,

Amy Schutz‐Geschwender,

Jeff A. Harford

et al.

Analytical Biochemistry, Journal Year: 2020, Volume and Issue: 593, P. 113608 - 113608

Published: Jan. 31, 2020

Attaining true quantitative data from WB requires that all the players involved in procedure are quality controlled including user. Appropriate protein extraction method, electrophoresis, and transfer of proteins, immunodetection blotted by antibodies, ultimate step imaging analyzing is nothing short a symphony. Like with any other technology life-sciences research, Western blotting can produce erroneous irreproducible data. We provide systematic approach to generate blot experiments incorporates critical validation steps identify minimize sources error variability throughout process.

Language: Английский

Citations

287
Defining the age-dependent and tissue-specific circadian transcriptome in male mice DOI Creative Commons
Christopher A. Wolff, Miguel A. Gutiérrez-Monreal, Lingsong Meng

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(1), P. 111982 - 111982

Published: Jan. 1, 2023

Cellular circadian clocks direct a daily transcriptional program that supports homeostasis and resilience. Emerging evidence has demonstrated age-associated changes in functions. To define age-dependent at the systems level, we profile transcriptome hypothalamus, lung, heart, kidney, skeletal muscle, adrenal gland three age groups. We find tissue-specific clock output changes. Aging reduces number of rhythmically expressed genes (REGs), indicative weakened control. REGs are enriched for hallmarks aging, adding another dimension to our understanding aging. Analyzing differential gene expression within tissue four different times day identifies distinct clusters differentially (DEGs). Increased variability across is common feature aged tissues. This analysis extends landscape aging highlights impact on function temporal expression.

Language: Английский

Citations

89
The wrinkling of time: Aging, inflammation, oxidative stress, and the circadian clock in neurodegeneration DOI Creative Commons
Brian V. Lananna, Erik S. Musiek

Neurobiology of Disease, Journal Year: 2020, Volume and Issue: 139, P. 104832 - 104832

Published: March 13, 2020

A substantial body of research now implicates the circadian clock in regulation an array diverse biological processes including glial function, metabolism, peripheral immune responses, and redox homeostasis. Sleep abnormalities other forms disruption are common symptoms aging neurodegeneration. Circadian may also influence pathogenesis neurodegenerative diseases. The specific mechanisms governing interaction between systems, aging, system still being uncovered. Here, we review evidence supporting a bidirectional relationship system. Further, explore hypothesis that age-related deterioration exacerbate multiple pathogenic processes, priming brain for

Language: Английский

Citations

106
Daily blue-light exposure shortens lifespan and causes brain neurodegeneration in Drosophila DOI Creative Commons
Trevor R. Nash,

Eileen S. Chow,

Alexander D. Law

et al.

npj Aging and Mechanisms of Disease, Journal Year: 2019, Volume and Issue: 5(1)

Published: Oct. 17, 2019

Light is necessary for life, but prolonged exposure to artificial light a matter of increasing health concern. Humans are exposed increased amounts in the blue spectrum produced by light-emitting diodes (LEDs), which can interfere with normal sleep cycles. The LED technologies relatively new; therefore, long-term effects across lifespan not understood. We investigated model organism, Drosophila melanogaster, and determined that flies maintained daily cycles 12-h darkness had significantly reduced longevity compared constant or white wavelengths blocked. Exposure adult 12 h per day accelerated aging phenotypes causing damage retinal cells, brain neurodegeneration, impaired locomotion. report locomotor impairments do depend on degeneration retina, as these were evident under genetically ablated eyes. Blue induces expression stress-responsive genes old young, suggesting cumulative acts stressor during aging. also several known blue-light-sensitive proteins acting pathways mediating detrimental effects. Our study reveals unexpected fly establishes investigate at cellular organismal level.

Language: Английский

Citations

80
Transcriptome profiling of aging Drosophila photoreceptors reveals gene expression trends that correlate with visual senescence DOI Creative Commons
Hana Hall,

Patrick Medina,

Daphne Cooper

et al.

BMC Genomics, Journal Year: 2017, Volume and Issue: 18(1)

Published: Nov. 21, 2017

Aging is associated with functional decline of neurons and increased incidence both neurodegenerative ocular disease. Photoreceptor in Drosophila melanogaster provide a powerful model for studying the molecular changes involved senescence since decreased visual behavior precedes retinal degeneration. Here, we sought to identify gene expression genomic features differentially regulated genes photoreceptors that contribute senescence.To could lead senescence, characterized aging transcriptome sensory highly enriched photoreceptors. We profiled nuclear genetically-labeled over 40 day time course identified stress DNA damage response, required neuronal function. further show combinations promoter motifs robustly age-regulated genes, suggesting transcription factors are important driving However, long, expressed heavily spliced also more likely be downregulated age, indicating other mechanisms at these genes. Lastly, circular RNAs (circRNAs) strongly increase during photoreceptors.Overall, account senescence. Further, predict age-related changes, potential targeted slow rate age-associated decline.

Language: Английский

Citations

83
Molecular Connections Between Circadian Clocks and Aging DOI
Patrick-Simon Welz, Salvador Aznar Benitah

Journal of Molecular Biology, Journal Year: 2019, Volume and Issue: 432(12), P. 3661 - 3679

Published: Dec. 27, 2019

Language: Английский

Citations

70
Circadian Regulation of Adult Stem Cell Homeostasis and Aging DOI Creative Commons
Salvador Aznar Benitah, Patrick-Simon Welz

Cell stem cell, Journal Year: 2020, Volume and Issue: 26(6), P. 817 - 831

Published: June 1, 2020

Language: Английский

Citations

70
Genetic regulation of gene expression and splicing during a 10-year period of human aging DOI Creative Commons
Brunilda Balliu, Matthew G. Durrant,

Olivia de Goede

et al.

Genome biology, Journal Year: 2019, Volume and Issue: 20(1)

Published: Nov. 4, 2019

Molecular and cellular changes are intrinsic to aging age-related diseases. Prior cross-sectional studies have investigated the combined effects of age genetics on gene expression alternative splicing; however, there has been no long-term, longitudinal characterization these molecular changes, especially in older age.We perform RNA sequencing whole blood from same individuals at ages 70 80 quantify how expression, splicing, their genetic regulation altered during this 10-year period advanced a population individual level. We observe that more similar own profiles later life than other age. identify 1291 294 genes differentially expressed alternatively spliced with age, as well 529 outlying trajectories. Further, we strong correlation splicing between two ages, small subset tested showing reduction associations age.These findings demonstrate that, although transcriptome its is mostly stable late life, dynamic characterized by regulation, most likely due increasing environmental variance

Language: Английский

Citations

67