Neuronal knockdown of Cullin3 as a Drosophila model of autism spectrum disorder DOI Creative Commons
Samantha J. Tener,

Zhi Lin,

Scarlet J. Park

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 17, 2024

Abstract Mutations in Cullin-3 ( Cul3 ), a conserved gene encoding ubiquitin ligase, are strongly associated with autism spectrum disorder (ASD). Here, we characterize ASD-related pathologies caused by neuron-specific knockdown Drosophila . We confirmed that neuronal causes short sleep, paralleling sleep disturbances ASD. Because defects and ASD linked to metabolic dysregulation, tested the starvation response of flies; they starved faster had lower triacylglyceride levels than controls, suggesting homeostasis. is also characterized increased biomarkers oxidative stress; found sensitivity hyperoxia, an exogenous stress. Additional hallmarks deficits social interactions learning. Using courtship suppression assay measures memory prior courtship, reduced learning compared controls. Finally, depletion alters anatomy mushroom body, brain region required for sleep. Taken together, phenotypes flies establish these as genetic model study molecular cellular mechanisms underlying pathology, including stress dysregulation neurodevelopment.

Language: Английский

Hallmarks of aging: An expanding universe DOI Creative Commons
Carlos López‐Otín, Marı́a A. Blasco, Linda Partridge

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(2), P. 243 - 278

Published: Jan. 1, 2023

Language: Английский

Citations

2817
Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice DOI
Victoria A. Acosta-Rodríguez, Filipa Rijo‐Ferreira,

Mariko Izumo

et al.

Science, Journal Year: 2022, Volume and Issue: 376(6598), P. 1192 - 1202

Published: May 5, 2022

Caloric restriction (CR) prolongs life span, yet the mechanisms by which it does so remain poorly understood. Under CR, mice self-impose chronic cycles of 2-hour feeding and 22-hour fasting, raising question if is calories, or time day that cause this increased span. We show here 30% CR was sufficient to extend span 10%; however, a daily fasting interval circadian alignment acted together 35% in male C57BL/6J mice. These effects were independent body weight. Aging induced widespread increases gene expression associated with inflammation decreases genes encoding components metabolic pathways liver from ad libitum-fed at night ameliorated these aging-related changes. Our results interventions promote longevity provide perspective further explore aging.

Language: Английский

Citations

253
Nutrition, longevity and disease: From molecular mechanisms to interventions DOI Creative Commons
Valter D. Longo, Rozalyn M. Anderson

Cell, Journal Year: 2022, Volume and Issue: 185(9), P. 1455 - 1470

Published: April 1, 2022

Diet as a whole, encompassing food composition, calorie intake, and the length frequency of fasting periods, affects time span in which health functional capacity are maintained. Here, we analyze aging nutrition studies simple organisms, rodents, monkeys, humans to link longevity conserved growth metabolic pathways outline their role age-related disease. We focus on feasible nutritional strategies shown delay and/or prevent diseases through epidemiological, model organism, clinical, centenarian underline need avoid malnourishment frailty. These findings integrated define diet based multi-pillar approach adjusted for age status optimize lifespan healthspan humans.

Language: Английский

Citations

222
Dietary regulation in health and disease DOI Creative Commons
Qi Wu,

Zhijie Gao,

Xin Yu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 23, 2022

Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan delaying ageing various species such as yeast, drosophila, rodent, primate human. It emerges develop precision-nutrition therapeutics slow age-related biological processes treat diverse diseases. However, nutritive advantages frequently diversify among individuals well organs tissues, which brings challenges this field. In review, we summarize different forms of dietary interventions extensively prescribed improvement disease treatment pre-clinical or clinical. We discuss nutrient-mediated mechanisms including metabolic regulators, metabolism pathways, epigenetic circadian clocks. Comparably, describe diet-responsive effectors by influence endocrinic, immunological, microbial neural states responsible improving health preventing multiple diseases humans. Furthermore, expatiate patterns dietotheroapies, fasting, calorie-restricted diet, ketogenic high-fibre plants-based protein restriction diet with specific reduction amino acids microelements, potentially affecting morbid states. Altogether, emphasize profound nutritional therapy, highlight crosstalk explored critical factors individualized therapeutic approaches predictors.

Language: Английский

Citations

99
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
Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases DOI Creative Commons

Shuaifei Ji,

Mingchen Xiong,

Huating Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 14, 2023

Abstract The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition deteriorated disorders. Rejuvenation refers giving aged cells or organisms youthful characteristics through various techniques, such as reprogramming and epigenetic regulation. great leaps in rejuvenation prove that not one-way street, many rejuvenative interventions have emerged delay even reverse the process. Defining mechanism by which roadblocks signaling inputs influence complex programs essential for understanding developing strategies. Here, we discuss intrinsic extrinsic factors counteract cell rejuvenation, targeted core mechanisms involved this Then, critically summarize latest advances state-of-art strategies of rejuvenation. Various methods also provide insights treating specific ageing-related diseases, including reprogramming, removal senescence (SCs) suppression senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune heterochronic transplantation, etc. potential applications therapy extend cancer treatment. Finally, analyze detail therapeutic opportunities challenges technology. Deciphering will further into anti-ageing disease treatment clinical settings.

Language: Английский

Citations

79
Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals DOI Creative Commons
Shaunak Deota, Terry Lin, Amandine Chaix

et al.

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(1), P. 150 - 165.e4

Published: Jan. 1, 2023

Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention that involves a daily cycle of and fasting. In both animals humans, TRF has pleiotropic health benefits arise from multiple organ systems, yet the molecular basis TRF-mediated not well understood. Here, we subjected mice to isocaloric ad libitum (ALF) or western diet examined gene expression changes in samples taken 22 organs brain regions collected every 2 h over 24-h period. We discovered profoundly impacts expression. Nearly 80% all genes show differential rhythmicity under at least one tissue. Functional annotation these revealed tissue- pathway-specific TRF. These findings resources provide critical foundation for future mechanistic studies will help guide human time-restricted eating (TRE) interventions treat various disease conditions with without pharmacotherapies.

Language: Английский

Citations

68
When a calorie is not just a calorie: Diet quality and timing as mediators of metabolism and healthy aging DOI Creative Commons
Maria M. Mihaylova, Amandine Chaix, Mirela Delibegović

et al.

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(7), P. 1114 - 1131

Published: June 30, 2023

Language: Английский

Citations

50
The microbiome stabilizes circadian rhythms in the gut DOI Creative Commons

Yueliang Zhang,

Yongjun Li, Annika F. Barber

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(5)

Published: Jan. 23, 2023

The gut microbiome is well known to impact host physiology and health. Given widespread control of by circadian clocks, we asked how the interacts with rhythms in Drosophila gut. did not cycle flies fed ad libitum, timed feeding (TF) drove limited cycling only clockless per01 flies. However, TF loss influenced composition transcriptome, independently together. Moreover, both interventions increased amplitude rhythmic gene expression, effects at least partly due changes histone acetylation. Contrary expectations, rendered animals more sensitive stress. Analysis function revealed that germ-free reset rapidly shifts light:dark cycle. We propose stabilizes prevent rapid fluctuations changing environmental conditions.

Language: Английский

Citations

42
Spermidine is essential for fasting-mediated autophagy and longevity DOI Creative Commons
Sebastian J. Hofer, Ioanna Daskalaki, Martina Bergmann

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(9), P. 1571 - 1584

Published: Aug. 8, 2024

Abstract Caloric restriction and intermittent fasting prolong the lifespan healthspan of model organisms improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection reduced incidence cardiovascular neurodegenerative diseases across species borders. Here, we asked whether cellular physiological consequences caloric depend on metabolism. We report that levels increased upon distinct regimens or in yeast, flies, mice volunteers. Genetic pharmacological blockade endogenous synthesis fasting-induced nematodes cells. Furthermore, perturbing pathway vivo abrogated lifespan- healthspan-extending effects, as well cardioprotective anti-arthritic fasting. Mechanistically, mediated these effects via induction hypusination translation regulator eIF5A. In summary, polyamine–hypusination axis emerges a phylogenetically conserved metabolic control hub for fasting-mediated enhancement longevity.

Language: Английский

Citations

32