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Donor type linked to distinct gene activity in human livers

Activity of 1,548 genes differed between livers donated after brain death and circulatory death, including patterns linked to senescence, when cells stop dividing.

Paper by Adam M. Thorne, Sabrina Stimmeder, Kirill Ustyantsev, +6 more authorsVincent Erwin de Meijer · University Medical Center Groningen Groningen the Netherlands
Graphical abstract from Aging Cell
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Graphical abstract. Thorne et al., CC BY

Our read

Mechanisms
Studied:
Cross-sectional study of 66 people (Independent replication, registered NCT03272841)
In the record:
One of 4 papers on donation after circulatory death on record: 2 with results in people.

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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Sixty-six human donor livers were compared before transplantation in an observational analysis: 24 donated after brain death and 42 after circulatory death. Median donor ages were 55 and 67 years, respectively. Tissue samples were collected after transport in cold storage.

The researchers measured gene activity, including patterns associated with senescence. These patterns differed by donor type and overlapped with injury responses. Livers donated after circulatory death showed stronger gene activity patterns related to immune activation and injury. Those donated after brain death showed stronger patterns related to metabolism, among other processes. Data from an independent cohort of 18 livers donated after circulatory death and 29 after brain death also showed differences by donor type, including in the available senescence-associated genes.

Why it matters

Senescence-associated signals may influence transplanted liver function, the authors suggest. They propose these signals as possible targets for drugs that kill senescent cells or modify their activity.

Caveats

The gene panels also captured inflammation and injury responses, so differences in these measures do not isolate senescence from those processes.

Where the evidence stands

Donation after circulatory death

Humans: a single group. Cells, worms or flies and mice: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

  • 1 lab

Angiogenesis

Cells, mice and humans: replicated by independent labs. Worms or flies: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 213 independent labs in 33 countries
  • 17 findings against
  • Funders: National Natural Science Foundation of China and others
  • 26 of 418 findings with company ties

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