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
Jamila Aug 06, 2020