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Journal Club July – Diluting Blood Plasma Rejuvenates Old Mice

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The Journal Club returns this Tuesday, July 28th, at 12:00 PM EDT / 5 PM UK, with your host Dr. Oliver Medvedik, livestreamed to our Facebook page. We will be taking a look at the recent study published by Dr. Irina Conboy and her team [1].

The study showed that by replacing half of the blood plasma in old mice with a saline and albumin mixture, with the albumin replacing the lost protein of the original plasma, they could achieve similar or even greater rejuvenation effects in brain, liver, and muscle tissues as joining two mice together through parabiosis or giving old mice young blood.

Heterochronic blood sharing rejuvenates old tissues, and most of the studies on how this works focus on young plasma, its fractions, and a few youthful systemic candidates. However, it was not formally established that young blood is necessary for this multi-tissue rejuvenation. Here, using our recently developed small animal blood exchange process, we replaced half of the plasma in mice with saline containing 5% albumin (terming it a “neutral” age blood exchange, NBE) thus diluting the plasma factors and replenishing the albumin that would be diminished if only saline was used. Our data demonstrate that a single NBE suffices to meet or exceed the rejuvenative effects of enhancing muscle repair, reducing liver adiposity and fibrosis, and increasing hippocampal neurogenesis in old mice, all the key outcomes seen after blood heterochronicity. Comparative proteomic analysis on serum from NBE, and from a similar human clinical procedure of therapeutic plasma exchange (TPE), revealed a molecular re-setting of the systemic signaling milieu, interestingly, elevating the levels of some proteins, which broadly coordinate tissue maintenance and repair and promote immune responses. Moreover, a single TPE yielded functional blood rejuvenation, abrogating the typical old serum inhibition of progenitor cell proliferation. Ectopically added albumin does not seem to be the sole determinant of such rejuvenation, and levels of albumin do not decrease with age nor are increased by NBE/TPE. A model of action (supported by a large body of published data) is that significant dilution of autoregulatory proteins that crosstalk to multiple signaling pathways (with their own feedback loops) would, through changes in gene expression, have long-lasting molecular and functional effects that are consistent with our observations. This work improves our understanding of the systemic paradigms of multi-tissue rejuvenation and suggest a novel and immediate use of the FDA approved TPE for improving the health and resilience of older people.

Join us live on Tuesday 28th July at 12:00 EDT on our Facebook page, where we will review the study and discuss the findings. As additional background, you may also wish to read our interview with Drs. Irina and Michael Conboy, which we did shortly after the study was published.

As usual, the Lifespan Heroes, our monthly patrons, will have the opportunity to join us live on the call to join in with the discussion directly. If you are interested in becoming a Lifespan Hero, you can learn more about that here.

Literature

[1] Mehdipour, M., Skinner, C., Wong, N., Lieb, M., Liu, C., Etienne, J., … & Conboy, I. M. (2020). Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin. Aging (Albany NY), 12(10), 8790.

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