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Molecular hallmarks of heterochronic parabiosis at single-cell resolution
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Molecular hallmarks of heterochronic parabiosis at single-cell resolution
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Journal Article
Molecular hallmarks of heterochronic parabiosis at single-cell resolution
2022
Overview
The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality
1
. Although an increasing number of interventions show promise for rejuvenation
2
, their effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. Here we performed single-cell RNA sequencing on 20 organs to reveal cell-type-specific responses to young and aged blood in heterochronic parabiosis. Adipose mesenchymal stromal cells, haematopoietic stem cells and hepatocytes are among those cell types that are especially responsive. On the pathway level, young blood invokes new gene sets in addition to reversing established ageing patterns, with the global rescue of genes encoding electron transport chain subunits pinpointing a prominent role of mitochondrial function in parabiosis-mediated rejuvenation. We observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it in select cell types. Together, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity.
A transcriptomics study demonstrates cell-type-specific responses to differentially aged blood and shows young blood to have restorative and rejuvenating effects that may be invoked through enhanced mitochondrial function.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
