Aging Fly Cell Atlas Identifies Exhaustive Aging Features at Cellular Resolution DOI Creative Commons
Tzu‐Chiao Lu, Maria Brbić, Ye-Jin Park

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Dec. 7, 2022

Abstract Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across organism remain unclear. Here, we present Fly Cell Atlas, single-nucleus transcriptomic map of whole aging Drosophila . We characterize 163 distinct cell types and perform an in-depth analysis composition, gene expression, identities. further develop clock models to predict fly age show that ribosomal expression conserved predictive factor for age. Combining all features, find unique type-specific patterns. This atlas provides valuable resource studying fundamental principles complex organisms.

Language: Английский

Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution DOI
Tzu‐Chiao Lu, Maria Brbić, Ye-Jin Park

et al.

Science, Journal Year: 2023, Volume and Issue: 380(6650)

Published: June 15, 2023

Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across organism remain unclear. Here, we present Fly Cell Atlas, single-nucleus transcriptomic map of whole aging

Language: Английский

Citations

67
The neuron-specific IIS/FOXO transcriptome in aged animals reveals regulatory mechanisms of cognitive aging DOI Creative Commons
Yifei Weng, Shiyi Zhou, Katherine Morillo

et al.

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

Citations

7
Adult Single-nucleus Neuronal Transcriptomes of Insulin Signaling Mutants Reveal Regulators of Behavior and Learning DOI Open Access
Jonathan St. Ange, Yifei Weng, Morgan E. Stevenson

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 7, 2024

Abstract The insulin/insulin-like signaling (IIS) pathway regulates many of C. elegans’ adult functions, including learning and memory 1 . While whole-worm tissue-specific transcriptomic analyses have identified IIS targets 2,3 , a higher-resolution single-cell approach is required to identify changes that confer neuron-specific improvements in the long-lived insulin receptor mutant, daf-2 To understand how behaviors are controlled by small number neurons change mutants, we used deep resolution single-nucleus RNA sequencing define each neuron type’s transcriptome wild-type mutants. First, found surprising differences between L4 larval young chemoreceptor expression, synaptic genes, genes. These Day transcriptomes allowed us AWC-specific regulators chemosensory function predict neuron-to-neuron peptide/receptor pairs. We then gene expression correlate with daf-2’s improved cognitive particularly AWC sensory controls associative 4 behavioral assays test their roles function. Combining single-neuron transcriptomics, genetic manipulation, enabled genes may single control behavior, conserved memory. One-Sentence Summary Single-nucleus elegans reveals functionally relevant transcriptional changes, chemosensation, learning,

Language: Английский

Citations

5
Considering Caenorhabditis elegans Aging on a Temporal and Tissue Scale: The Case of Insulin/IGF-1 Signaling DOI Creative Commons
Paola Fabrizio,

Allan Alcolei,

Florence Solari

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 288 - 288

Published: Feb. 5, 2024

The aging process is inherently complex, involving multiple mechanisms that interact at different biological scales. nematode

Language: Английский

Citations

4
Chromatin: the old and young of it DOI Creative Commons
Felicity J. Emerson, Siu Sylvia Lee

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Oct. 9, 2023

Aging affects nearly all aspects of our cells, from DNA to proteins how cells handle stress and communicate with each other. Age-related chromatin changes are particular interest because can dynamically respond the cellular organismal environment, many modifications at reversible. Changes occur during aging, evidence model organisms suggests that factors could play a role in modulating aging process itself, as altering work often affect lifespan yeast, worms, flies, mice. The field is rapidly expanding, high-resolution genomics tools make it possible survey environment or track implicated longevity precision was not previously possible. In this review, we discuss state research. We include examples Drosophila , mice, humans, but particularly focus on commonly used model, worm Caenorhabditis elegans which there modulate longevity. both age-related specific linked core histones, nuclear architecture, remodeling, histone modifications.

Language: Английский

Citations

8
The Neuron-specific IIS/FOXO Transcriptome in Aged Animals Reveals Regulatory Mechanisms of Cognitive Aging DOI Open Access
Yifei Weng, Shiyi Zhou, Katherine Morillo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 29, 2023

Abstract 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

Citations

4
Single-cell phylotranscriptomics of developmental and cell type evolution DOI
Fuqiang Ma, Chaogu Zheng

Trends in Genetics, Journal Year: 2024, Volume and Issue: 40(6), P. 495 - 510

Published: March 14, 2024

Language: Английский

Citations

1
Adult single-nucleus neuronal transcriptomes of insulin signaling mutants reveal regulators of behavior and learning DOI Creative Commons
Jonathan St. Ange, Yifei Weng, Rachel Kaletsky

et al.

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

Published: Dec. 1, 2024

Language: Английский

Citations

1
Bridge-Like Lipid Transfer Proteins (BLTPs) in C. elegans: From Genetics to Structures and Functions DOI Creative Commons
Taruna Pandey, Jianxiu Zhang, Bingying Wang

et al.

Contact, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

In eukaryotic cells, lipid transfer can occur at membrane contact sites (MCS) to facilitate the exchange of various lipids between two adjacent cellular organelle membranes. Lipid proteins (LTPs), including shuttle LTP or bridge-like (BLTP), transport MCS and are critical for diverse processes, metabolism, trafficking, cell signaling. BLTPs (BLTP1-5, ATG2 VPS13 family proteins) contain lipid-accommodating hydrophobic repeating β-groove (RBG) domains that allow bulk through MCS. Compared with vesicular LTP, have been only recently identified. Their functions regulatory mechanisms currently being unraveled in model organisms by approaches. this review, we summarize genetics, structural features, biological BLTP genetically tractable organism C. elegans. We discuss our recent studies findings on elegans LPD-3, a prototypical megaprotein ortholog BLTP1, identified evolutionarily conserved multicellular human cells. also highlight areas future research using complementary systems Given emerging links several diseases, Parkinson's disease Alkuraya-Kučinskas syndrome, discovering roles their regulation action should contribute new advances basic biology potential therapeutic development related disorders.

Language: Английский

Citations

3
The Neuron-specific IIS/FOXO Transcriptome in Aged Animals Reveals Regulatory Mechanisms of Cognitive Aging DOI Open Access
Yifei Weng, Shiyi Zhou, Katherine Morillo

et al.

Published: March 27, 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

Citations

0