Molecular hallmarks of heterochronic parabiosis at single-cell resolution

Róbert Pálovics, Andreas Keller (), Nicholas Schaum, Weilun Tan, Tobias Fehlmann, Michael Borja, Fabian Kern, Liana Bonanno, Kruti Calcuttawala, James Webber, Aaron McGeever, Jian Luo, Angela Oliveira Pisco, Jim Karkanias, Norma F. Neff, Spyros Darmanis (), Stephen R. Quake () and Tony Wyss-Coray ()
Additional contact information
Róbert Pálovics: Stanford University School of Medicine
Andreas Keller: Stanford University School of Medicine
Nicholas Schaum: Stanford University School of Medicine
Weilun Tan: Chan Zuckerberg Biohub
Tobias Fehlmann: Saarland University
Michael Borja: Chan Zuckerberg Biohub
Fabian Kern: Saarland University
Liana Bonanno: Stanford University School of Medicine
Kruti Calcuttawala: Stanford University School of Medicine
James Webber: Chan Zuckerberg Biohub
Aaron McGeever: Chan Zuckerberg Biohub
Jian Luo: Veterans Administration Palo Alto Healthcare System
Angela Oliveira Pisco: Chan Zuckerberg Biohub
Jim Karkanias: Chan Zuckerberg Biohub
Norma F. Neff: Chan Zuckerberg Biohub
Spyros Darmanis: Chan Zuckerberg Biohub
Stephen R. Quake: Chan Zuckerberg Biohub
Tony Wyss-Coray: Stanford University School of Medicine

Nature, 2022, vol. 603, issue 7900, 309-314

Abstract: Abstract The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality1. Although an increasing number of interventions show promise for rejuvenation2, 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.

Date: 2022
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DOI: 10.1038/s41586-022-04461-2

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