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

• Published in: Nature communications Vol. 7; no. 1; p. 13363
• Main Authors: Rebo, Justin, Mehdipour, Melod, Gathwala, Ranveer, Causey, Keith, Liu, Yan, Conboy, Michael J., Conboy, Irina M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.11.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/100; 13/51; 13/62; 13/95; 631/1647; 631/443/7; 64; 64/60; Aging; Animal cognition; Animals; Blood; Blood circulation; Blood Transfusion; Cellular Senescence; Circulatory system; Exchanging; Humanities and Social Sciences; Male; Mice; Mice, Inbred C57BL; multidisciplinary; Muscles; Myogenesis; Neurogenesis; Organs; Parabiosis; Physical Endurance; Plasma; Rejuvenation; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; Stem Cells - physiology; Tissues; United States > US; California
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13363

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. Joining the circulatory system of an old with a young animal has been shown to rejuvenate old tissues. Here the authors describe a comparatively simple blood infusion system that allows for the controlled exchange of blood between two animals, and study the effects of a single exchange on various tissues.