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Molecular hallmarks of heterochronic parabiosis at single-cell resolution
Róbert Pálovics1, Andreas Keller2,3, Nicholas Schaum1
1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
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.
Insights
Reversing biological aging is possible. Young blood can rejuvenate specific cell types and restore gene expression, highlighting the role of mitochondrial function in the aging process.
Area of Science:
- Gerontology and molecular biology
- Cellular and molecular mechanisms of aging
Background:
- Interventions for rejuvenation show promise but their effects on diverse cell types and molecular pathways are not fully understood.
- Biological aging impacts disease risk and vitality, making rejuvenation a key research area.
Purpose of the Study:
- To investigate cell-type-specific responses to young and aged blood using heterochronic parabiosis.
- To explore the molecular pathways involved in parabiosis-mediated rejuvenation.
Main Methods:
- Single-cell RNA sequencing was performed on cells from 20 organs.
- Heterochronic parabiosis was used to analyze the effects of young and aged blood.
Main Results:
- Adipose mesenchymal stromal cells, hematopoietic stem cells, and hepatocytes showed significant responsiveness to young blood.
- Young blood reversed aging patterns by restoring gene expression, particularly for electron transport chain subunits, indicating a role for mitochondrial function.
- Aged blood reduced global gene expression, while young blood restored it in specific cell types.
Conclusions:
- Young blood can rejuvenate specific cell types and restore gene expression patterns associated with aging.
- Mitochondrial function plays a crucial role in parabiosis-mediated rejuvenation.
- Blood-borne factors significantly influence cellular integrity and aging processes.
