Molecular hallmarks of heterochronic parabiosis at single-cell resolution

Molecular hallmarks of heterochronic parabiosis at single-cell resolution. Pálovics, R., Keller, A., Schaum, N., Tan, W., Fehlmann, T., Borja, M., Kern, F., Bonanno, L., Calcuttawala, K., Webber, J., Mcgeever, A., Consortium, T. T. M., Luo, J., Pisco, A. O., Karkanias, J., Neff, N. F., Darmanis, S., Quake, S. R., & Wyss-Coray, T. Nature, 603:1-6, 03, 2022.

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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.

@article{safjrt5362,
	author = {Pálovics, Róbert and Keller, Andreas and Schaum, Nick and Tan, Weilun and Fehlmann, Tobias and Borja, Michael and Kern, Fabian and Bonanno, Liana and Calcuttawala, Kruti and Webber, James and Mcgeever, Aaron and The Tabula Muris Consortium and Luo, Jian and Pisco, Angela Oliveira and Karkanias, Jim and Neff, Norma F. and Darmanis, Spyros and Quake, Stephen R. and Wyss-Coray, Tony},
	year = {2022},
	month = {03},
	pages = {1-6},
	title = "{Molecular hallmarks of heterochronic parabiosis at single-cell resolution}",
	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.}",
	volume = {603},
	journal = {Nature},
	doi = {10.1038/s41586-022-04461-2},
	URL = {https://www.nature.com/articles/s41586-022-04461-2},
}

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