The neuron-specific IIS/FOXO transcriptome in aged animals reveals regulatory mechanisms of cognitive aging

eLife, Journal Year: 2024, Volume and Issue: 13

Published: April 8, 2024

Cognitive decline is a significant health concern in our aging society. Here, we used the model organism C. elegans to investigate impact of IIS/FOXO pathway on age-related cognitive decline. The daf-2 Insulin/IGF-1 receptor mutant exhibits extension learning and memory span with age compared wild-type worms, an effect that dependent DAF-16 transcription factor. To identify possible mechanisms by which mutants maintain while worms lose neuronal function, carried out neuron-specific transcriptomic analysis aged animals. We observed downregulation genes upregulation transcriptional regulation neurons. By contrast, exhibit distinct alterations response aging, including stress specific insulin signaling genes. tested roles significantly transcriptionally-changed regulating functions, identifying novel regulators memory. In addition other mechanistic insights, comparison vs young transcriptome revealed new set potentially neuroprotective upregulated; instead simply mimicking state, may enhance resilience accumulation harm take more active approach combat aging. These findings suggest potential mechanism for function offer insights into therapeutic targets

Language: Английский

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Male-specific behavioral and transcriptomic changes in aging C. elegans neurons

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109910 - 109910

Published: May 8, 2024

Aging is a complex biological process with sexually dimorphic aspects. Although cognitive aging of

Language: Английский

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Optimising Age‐Specific Insulin Signalling to Slow Down Reproductive Ageing Increases Fitness in Different Nutritional Environments

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

ABSTRACT The developmental theory of ageing proposes that age‐specific decline in the force natural selection results suboptimal levels gene expression adulthood, leading to functional senescence. This explicitly predicts optimising adulthood can ameliorate senescence and improve fitness. Reduced insulin/IGF‐1 signalling (rIIS) extends reproductive lifespan Caenorhabditis elegans at cost reduced reproduction. Here, we show adulthood‐only rIIS improves late‐life reproduction without any detrimental effects on other life‐history traits both benign stressful conditions. Remarkably, additively when animals are exposed a fluctuating food environment—intermittent fasting (IF)—resulting intake early adulthood. Full factorial genome‐wide RNA‐Seq across life course demonstrated IF modulate pro‐longevity genes. IF, combined + treatment downregulated genes involved biosynthesis differentially regulated immunity later life. Importantly, uniquely large cluster mid‐life associated with immune response. These suggest decelerate increase

Language: Английский

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Administration of Polyphenol-Rich Sugarcane Extract Alleviates Deficits Induced by Amyloid-Beta1–42 (Aβ1–42) in Transgenic C. elegans

Journal of Ageing and Longevity, Journal Year: 2025, Volume and Issue: 5(2), P. 12 - 12

Published: April 2, 2025

Polyphenol-Rich Sugarcane Extract (PRSE), derived from Saccharum officinarum, demonstrates significant neuroprotective effects against amyloid-beta (Aβ1–42)-induced deficits associated with Alzheimer’s disease (AD). This study utilized transgenic C. elegans expressing Aβ1–42 to investigate PRSE’s impact on lifespan, sensory behavior, learning, memory, and amyloid fibril accumulation. Supplementation 5 mg/mL of PRSE extended the mean lifespan worms by 11% (17.78 ± 0.36 days) reduced levels 34% in aged compared untreated worms. also improved a 27% increase naïve chemotaxis at day 8. Memory were mitigated, PRSE-treated showing 21% 30% reductions short-term associative memory loss after 1 h intervals days 8 12, respectively. These improvements can be polyphenolic compounds PRSE, which aid reducing aggregation. The findings highlight potential as dietary supplement address AD-related symptoms pathologies. Further studies are needed understand its mechanisms confirm effectiveness mammals, supporting use natural preventative for related neurodegenerative diseases.

Language: Английский

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Effect of structural changes of Rehmannia glutinosa polysaccharide before and after processing on anti-aging activity

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 309, P. 143168 - 143168

Published: April 14, 2025

Language: Английский

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WormCNN-Assisted Establishment and Analysis of Glycation Stress Models in C. elegans: Insights into Disease and Healthy Aging

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9675 - 9675

Published: Sept. 6, 2024

Glycation Stress (GS), induced by advanced glycation end-products (AGEs), significantly impacts aging processes. This study introduces a new model of GS Caenorhabditis elegans feeding them Escherichia coli OP50 cultured in glucose-enriched medium, which better simulates human dietary compared to previous single protein–glucose cross-linking methods. Utilizing WormCNN, deep learning model, we assessed the health status and calculated Healthy Aging Index (HAI) worms with or without GS. Our results demonstrated accelerated group, evidenced increased autofluorescence altered gene expression key regulators, daf-2 daf-16. Additionally, observed elevated pharyngeal pumping rates AGEs-fed worms, suggesting an addictive response similar patterns. highlights profound effects on worm underscores critical role computer vision accurately assessing aiding establishment disease models. The findings provide insights into glycation-induced offer comprehensive approach studying

Language: Английский

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Adult single-nucleus neuronal transcriptomes of insulin signaling mutants reveal regulators of behavior and learning

Cell Genomics, Journal Year: 2024, Volume and Issue: unknown, P. 100720 - 100720

Published: Dec. 1, 2024

Language: Английский

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