A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood

Justin Rebo, Melod Mehdipour, Ranveer Gathwala, Keith Causey, Yan Liu, Michael J. Conboy () and Irina M. Conboy ()
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Justin Rebo: 174 Stanley Hall, University of California, Berkeley, Berkeley, California 94720-3220, USA
Melod Mehdipour: 174 Stanley Hall, University of California, Berkeley, Berkeley, California 94720-3220, USA
Ranveer Gathwala: 174 Stanley Hall, University of California, Berkeley, Berkeley, California 94720-3220, USA
Keith Causey: SENS Research Foundation, 110 Pioneer Way, Suite J
Yan Liu: 174 Stanley Hall, University of California, Berkeley, Berkeley, California 94720-3220, USA
Michael J. Conboy: 174 Stanley Hall, University of California, Berkeley, Berkeley, California 94720-3220, USA
Irina M. Conboy: 174 Stanley Hall, University of California, Berkeley, Berkeley, California 94720-3220, USA

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract Heterochronic parabiosis rejuvenates the performance of old tissue stem cells at some expense to the young, but whether this is through shared circulation or shared organs is unclear. Here we show that heterochronic blood exchange between young and old mice without sharing other organs, affects tissues within a few days, and leads to different outcomes than heterochronic parabiosis. Investigating muscle, liver and brain hippocampus, in the presence or absence of muscle injury, we find that, in many cases, the inhibitory effects of old blood are more pronounced than the benefits of young, and that peripheral tissue injury compounds the negative effects. We also explore mechanistic explanations, including the role of B2M and TGF-beta. We conclude that, compared with heterochronic parabiosis, heterochronic blood exchange in small animals is less invasive and enables better-controlled studies with more immediate translation to therapies for humans.

Date: 2016
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DOI: 10.1038/ncomms13363

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