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Gene Expression Patterns in Suspended Animation

Image credit: Kim et al. 2016 (https://dmm.biologists.org/content/9/2/115)

Jamila Aug 06, 2020
Are there any gene expression patterns that are conserved across different types of suspended animation?
Suspended animation is when biological functions are slowed down or even stopped completely! Brunet and colleagues research diapause in the African turquoise killifish (Nothobranchius furzeri). The killifish is native to Mozambique and Zimbabwe and resides in ponds that experience severe drought; the pond is only available for four months a year. The killifish have adapted to this by having accelerated aging and mating whilst the pond is there and then the resulting embryos enter “diapause” during the drought. Therefore, the killifish embryos can survive during the drought. It has been suggested that diapause can for last months and even years, and it does not have any known negative effects on lifespan or biological function.

The researchers from the Brunet laboratory have found that the gene expression of autophagy, lipid metabolism, and nucleotide metabolism-related genes was significantly upregulated during diapause. Whereas, the gene expression of genes associated with cellular proliferation and organ development was reduced during diapause. Furthermore, the genes EZH1, CBX7, and PCGF5 are involved in the regulation of chromatin, these genes were found to be highly upregulated during diapause.

It would be interesting to see whether diapause and other methods of suspended animation (torpor and hibernation) share any gene expression patterns. This would help to determine if there are common features of suspended animation and help our understanding of how suspended animation works.

[1]Brunet, Anne. "Old and new models for the study of human ageing." Nature Reviews Molecular Cell Biology (2020): 1-3.

[2]Hu, Chi-Kuo, et al. "Vertebrate diapause preserves organisms long term through Polycomb complex members." Science 367.6480 (2020): 870-874.

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PcG in hibernating animals and link across suspended animation, calorie conservation, and longevity

Shubhankar Kulkarni
Shubhankar Kulkarni Aug 10, 2020
Polycomb group of proteins (PcG) suppress the expression of potassium channels in the brain and in cultured neurons. This channel arrest that suppresses the cell membrane permeability to ions is a phenomenon observed in hibernation. This provides neuroprotection in the hypoxia-tolerant, calorie conserving, and hibernating species. [1] Both EZH2 ( (Enhancer of Zeste) and CBX7 are members of the Polycomb group of proteins. Interestingly, Polycomb group of proteins also help delay and/or inhibit senescence and can be used as targets for therapy. A PcG gene Bmi1 (also called PCGF4) is a key requirement for self-renewing cell divisions of both adult hematopoietic stem cells (HSC) and neural stem cells. Several studies demonstrate a role for Bmi1 in preventing senescence. Bmi1–/– fetal liver cells transplanted in mice could differentiate correctly but did not self-renew. [2] Human fetal lung fibroblasts were shown to have downregulated Bmi1 during senescence but not quiescence. [3] Bmi1 overexpression in fibroblasts increases life span of mice and man. [4] Wild-type mouse embryo fibroblasts undergo senescence after 7 to 8 passages in culture, but those from Bmi1–/– undergo only three passages before senescence. It was also shown that re-expression of Bmi1 reversed the premature senescence phenotype and overexpression of Bmi1 increased life span. Also, Sirtuin-2, a longevity protein, is also closely associated with EZH2 and is a part of the Polycomb repressive complex. [2] These studies suggest a link across suspended animation, calorie conservation, and longevity. References: 1. Stenzel-Poore MP, Stevens SL, Xiong Z, Lessov NS, Harrington CA, Mori M, et al. Effect of ischaemic preconditioning on genomic response to cerebral ischaemia: similarity to neuroprotective strategies in hibernation and hypoxia-tolerant states. Lancet [Internet]. 2003 Sep;362(9389):1028–37. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0140673603144121 2. Mishra K, Mishra RK. Polycomb Group of Genes and the Epigenetics of Aging. In: Epigenetics of Aging [Internet]. New York, NY: Springer New York; 2010. p. 135–50. Available from: http://link.springer.com/10.1007/978-1-4419-0639-7_8 3. Vonlanthen S, Heighway J, Altermatt HJ, Gugger M, Kappeler A, Borner MM, et al. The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression. Br J Cancer [Internet]. 2001 May 15;84(10):1372–6. Available from: http://www.nature.com/doifinder/10.1054/bjoc.2001.1791 4. Jacobs JJL, Kieboom K, Marino S, DePinho RA, van Lohuizen M. The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature [Internet]. 1999 Jan;397(6715):164–8. Available from: http://www.nature.com/articles/16476

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