Gene expression in the twilight of death

Olaru

et al. 2023

IJMS

In the clinic, the death certificate is issued if brain electrical activity is no longer detectable. However, recent research has shown that in model organisms and humans, gene activity continues for at least 96 h postmortem. The discovery that many genes are still working up to 48 h after death questions our definition of death and has implications for organ transplants and forensics. If genes can be active up to 48 h after death, is the person technically still alive at that point? We discovered a very interesting parallel between genes that were upregulated in the brain after death and genes upregulated in the brains that were subjected to medically-induced coma, including transcripts involved in neurotransmission, proteasomal degradation, apoptosis, inflammation, and most interestingly, cancer. Since these genes are involved in cellular proliferation, their activation after death could represent the cellular reaction to escape mortality and raises the question of organ viability and genetics used for transplantation after death. One factor limiting the organ availability for transplantation is religious belief. However, more recently, organ donation for the benefit of humans in need has been seen as “posthumous giving of organs and tissues can be a manifestation of love spreading also to the other side of death”.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Induced Coma, Death, and Organ Transplantation: A Physiologic, Genetic, and Theological Perspective

Olaru

et al. 2023

IJMS

“…Death is the cessation of biological functions that maintain homeostasis and sustain a living organism [ 54 ]. The death of an animal means that its systems, organs, tissues, and cells stop functioning as a whole, which implies that the individual parts may still be alive at the time when the body dies [ 54 ].…”

Section: The Aging Of the Circadian Clock In Drosophila mentioning

confidence: 99%

The Development and Decay of the Circadian Clock in Drosophila melanogaster

2019

The way in which the circadian clock mechanism develops and decays throughout life is interesting for a number of reasons and may give us insight into the process of aging itself. The Drosophila model has been proven invaluable for the study of the circadian clock and development and aging. Here we review the evidence for how the Drosophila clock develops and changes throughout life, and present a new conceptual model based on the results of our recent work. Firefly luciferase lines faithfully report the output of known clock genes at the central clock level in the brain and peripherally throughout the whole body. Our results show that the clock is functioning in embryogenesis far earlier than previously thought. This central clock in the fly remains robust throughout the life of the animal and only degrades immediately prior to death. However, at the peripheral (non-central oscillator level) the clock shows weakened output as the animal ages, suggesting the possibility of the breakdown in the cohesion of the circadian network.

“…The investigation of post-mortem RNA dynamics can provide novel insights into the biology of death. Previous studies have suggested that there is some level of active post-mortem mRNA transcription 1 – 4 . Although most of the transcriptome is shutting down or degrading, approximately 1% of the brain transcriptome is turned on in response to death 2 .…”

Section: Introductionmentioning

confidence: 99%

Insights into how environment shapes post-mortem RNA transcription in mouse brain

Bonadio

Nunes

Moretti

et al. 2021

Sci Rep

Most biological features that occur on the body after death were already deciphered by traditional medicine. However, the molecular mechanisms triggered in the cellular microenvironment are not fully comprehended yet. Previous studies reported gene expression alterations in the post-mortem condition, but little is known about how the environment could influence RNA degradation and transcriptional regulation. In this work, we analysed the transcriptome of mouse brain after death under three concealment simulations (air exposed, buried, and submerged). Our analyses identified 2,103 genes differentially expressed in all tested groups 48 h after death. Moreover, we identified 111 commonly upregulated and 497 commonly downregulated genes in mice from the concealment simulations. The gene functions shared by the individuals from the tested environments were associated with RNA homeostasis, inflammation, developmental processes, cell communication, cell proliferation, and lipid metabolism. Regarding the altered biological processes, we identified that the macroautophagy process was enriched in the upregulated genes and lipid metabolism was enriched in the downregulated genes. On the other hand, we also described a list of biomarkers associated with the submerged and buried groups, indicating that these environments can influence the post-mortem RNA abundance in its particular way.