Molecular hallmarks of heterochronic parabiosis at single-cell resolution

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.

Automated summary

Slowing or reversing biological ageing can have significant implications for disease risk reduction and maintaining vitality. However, there is still much to explore regarding the effectiveness of interventions on various cell types and molecular pathways. Through single-cell RNA sequencing on 20 organs, this study identified specific cell types, such as adipose mesenchymal stromal cells, haematopoietic stem cells, and hepatocytes, that respond to young and aged blood. Additionally, it was found that young blood not only reverses established ageing patterns but also activates new gene sets, particularly highlighting the role of mitochondrial function in rejuvenation.