Stem cells
© Nissam BenvenishtyHuman embryonic stem cells remain alive and attempt to repair themselves after death.
Even after someone is declared dead, life continues in the body, suggests a surprising new study with important implications.

Gene expression — when information stored in DNA is converted into instructions for making proteins or other molecules — actually increases in some cases after death, according to the new paper, which tracked postmortem activity and is published in the journal Open Biology.

"Not all cells are 'dead' when an organism dies," senior author Peter Noble of the University of Washington and Alabama State University told Seeker. "Different cell types have different life spans, generation times and resilience to extreme stress." In fact, some cells seem to fight to live after the organism has died. "It is likely that some cells remain alive and are attempting to repair themselves, specifically stem cells," Noble said.

Signs of Cellular Life

The international team of scientists, led by Alex Pozhitkov, studied zebrafish and mice and believe that the phenomenon occurs in all animals, including humans.

Gene transcription — the first step of gene expression, where a segment of DNA is copied into RNA — associated with stress, immunity, inflammation, cancer and other factors increased after death. And this could happen within hours or even days after the individual as a whole was declared dead.

Interestingly, gene transcription linked to embryonic development also increased. It's as though parts of the body essentially go back in time, exhibiting cellular characteristics of very early human development.

The Twilight of Death

The researchers identified a "step-wise shutdown" after death where some gene transcriptions diminished while others became more abundant. While the precise steps have yet to be defined, the scientists do not believe the process is random.

"Death is a time-dependent process," Noble remarked. "We have framed our discussion of death in reference to 'postmortem time' because on the one hand, there is no reason to suspect that minutes after an animal dies, gene transcription will abruptly stop."

"On the other hand," he added, "we know that within hours to days, the animal's body will eventually decompose by natural processes and gene transcription will end." The authors referred to the window of time between "death and the start of decomposition as the 'twilight of death' — when gene expression occurs, but not all of the cells are dead yet."

For years, researchers have noted that recipients of donor organs, such as livers, often exhibit increased risk of cancer following a transplant. The authors indicate there could be a link between "twilight of death" gene transcription and this increased cancer risk. "It might be useful to prescreen transplant organs for increased cancer gene transcripts," Noble said, which might offer some insight on the health of the organ, though more research is needed.

If such a connection is established, the findings could help to explain why the donated organs of people who were young and healthy before death — for example, if they died in a sudden accident — could still lead to increased risk of cancer in the organ recipient.

Since gene transcription associated with cancer and inflammation also can increase postmortem, analyzing those activities and patterns could shed light on how these health problems arise in the living and how the body reacts once they have been established.

Ashim Malhotra, an assistant professor at Pacific University Oregon who was not involved with the study, said "one would expect genes involved in immunity and inflammation to [increase in response to a stimulus] right after... death because some cells remain alive for a short time and the transcriptional machinery is still operating in 'life mode.'"

Malhotra was nevertheless surprised that the process happened between 24 to 48 hours after death. The researchers concluded their investigations after that upper time limit, so the transcription could potentially go on for longer than two days.

Perhaps certain cells live longer than we think, but there could be another explanation that has not yet been considered. Noble likens studying the dead to analyzing building collapses, in that both investigations can reveal what the original underlying structure was.

"Like the twin towers on 9-11, we can get a lot of information on how a system collapses by studying the sequence of events as they unfold through time," he said. "In the case of the twin towers, we saw a systematic collapse of one floor at a time that affected the floors underneath it. This gives us an idea of the structural foundations supporting the building and we see a similar pattern in the shutdown of animals."

Putting Death on Hold

Malhotra hopes that the experiments of Noble, Pozhitkov and their team could be repeated with more sampling times—possibly going beyond 48 hours—in order to better understand the identified transcriptional dynamics. Since the new study is the first comprehensive investigation to assess changes in genetic transcription after organismal death, many questions remain.

Malhotra even raised the big question of raising the presumed dead. He wonders now if it might be possible to "put a hold on death" if the molecular processes underlying cellular death could be further determined and if scientists could develop specific ways to "interrupt the shutdown."

Arne Traulsen of the Max Planck Institute for Evolutionary Biology also expressed excitement over future related research. "I think this could be the start of a much more detailed analysis on how processes are being shut down after organismal death," Traulsen explained to Seeker.

"In spirit, death is probably more like turning a computer off and much less like turning a light bulb off," he added, referring to the computer-like step-by-step shutdown and intricacies involved. "We will see the consequences of this at some point, but I would not be surprised if this (new research) provides entirely new insights on the function of complex biological systems."