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Heterochronic parabiosis reprograms the mouse brain transcriptome by shifting aging signatures in multiple cell types

ABSTRACT: Heterochronic parabiosis reprograms the mouse brain transcriptome by shifting aging signatures in multiple cell types

PROVIDER: PRJNA922313 | ENA |

REPOSITORIES: ENA

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Heterochronic parabiosis reprograms the mouse brain transcriptome by shifting aging signatures in multiple cell types

Project description:Aging is a complex process involving transcriptomic changes associated with deterioration across multiple tissues and organs, including the brain. Recent studies using heterochronic parabiosis have shown that various aspects of aging-associated decline are modifiable or even reversible. To better understand how this occurs, we performed single-cell transcriptomic profiling of young and old mouse brains following parabiosis. For each cell type, we catalogued alterations in gene expression, molecular pathways, transcriptional networks, ligand-receptor interactions, and senescence status. Our analyses identified gene signatures demonstrating that heterochronic parabiosis regulates several hallmarks of aging in a cell-type-specific manner. Brain endothelial cells were found to be especially malleable to this intervention, exhibiting dynamic transcriptional changes that affect vascular structure and function. These findings suggest novel strategies for slowing deterioration and driving regeneration in the aging brain through approaches that do not rely on disease-specific mechanisms or actions of individual circulating factors.

2023-01-14 | GSE222510 | GEO

Molecular hallmarks of heterochronic parabiosis at single cell resolution

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Molecular hallmarks of heterochronic parabiosis at single cell resolution

Project description:Single-cell RNA sequencing data of Mus Musculus heterochronic parabionts

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Characterizing expression changes in noncoding RNAs during aging and heterochronic parabiosis across mouse tissues

Project description:Molecular mechanisms of organismal and cell aging remain incompletely understood. We, therefore, generated a body-wide map of noncoding RNA (ncRNA) expression in aging (16 organs at ten timepoints from 1 to 27 months) and rejuvenated mice. We found molecular aging trajectories are largely tissue-specific except for eight broadly deregulated microRNAs (miRNAs). Their individual abundance mirrors their presence in circulating plasma and extracellular vesicles (EVs) whereas tissue-specific ncRNAs were less present. For miR-29c-3p, we observe the largest correlation with aging in solid organs, plasma and EVs. In mice rejuvenated by heterochronic parabiosis, miR-29c-3p was the most prominent miRNA restored to similar levels found in young liver. miR-29c-3p targets the extracellular matrix and secretion pathways, known to be implicated in aging. We provide a map of organism-wide expression of ncRNAs with aging and rejuvenation and identify a set of broadly deregulated miRNAs, which may function as systemic regulators of aging via plasma and EVs.

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DNA methylation changes in mice induced by mock parabiosis

Project description:Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. We characterized several models in which biological age, assessed primarily through analysis of DNA methylation, undergoes reversible changes. Heterochronic parabiosis is one such example.

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DNA methylation changes in mice induced by parabiosis and recovery [RRBS]

Project description:Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. We characterized several models in which biological age is perturbed. Heterochronic parabiosis and recovery from this procedure is one such example.

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Gene expression changes in mice induced by parabiosis and recovery [RNA-seq]

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Characterizing expression changes in noncoding RNAs during aging and heterochronic parabiosis across mouse tissues

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DNA methylation changes in mice induced by parabiosis and recovery [HorvathMammalMethylChip40]

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Gene expression profile in Liver of old mice after 5 weeks of Heterocronic parabiosis with Yg WT or Yg MANFHet mice

Project description:To ask whether MANF contributes to the rejuvenating effects of heterochronic parabiosis, we generated heterochronic pairs in which 20 month old WT mice were combined with either 4 month old MANFHet (O-YgHet) or WT (O-YgWT) littermates, and maintained for 5 weeks before analysis. Control pairs in which old WT mice were combined together (O-O) were used. Livers were collected from each animal in the pair and RNA was sequenced for 5 independent animals/condition.

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