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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE224442 | GEO | 2023/04/21

REPOSITORIES: GEO

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

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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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.

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Molecular hallmarks of heterochronic parabiosis at single cell resolution

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