This 2016 Finnish review subject was epigenetic effects of hypoxia:
“Ever since the Cambrian period, oxygen availability has been in the center of energy metabolism. Hypoxia stabilizes expression of hypoxia-inducible transcription factor-1α (HIF-1α), which controls expression of hundreds of survival genes related to enhanced energy metabolism and autophagy.
There are several other signals, mostly related to stresses, which can increase expression of HIF factors and thus improve cellular survival. However, a chronic activation of HIF factors can have detrimental effects, e.g. stimulate cellular senescence and tissue fibrosis commonly enhanced in age-related diseases.
Stabilization of HIF-1α increases expression of histone lysine demethylases (KDM). Hypoxia-inducible KDMs support locally the gene transcription induced by HIF-1α, although they can also control genome-wide chromatin landscape, especially KDMs which demethylate H3K9 and H3K27 sites (repressive epigenetic marks).”
Gene areas where HIF-1α is involved include:
Figure 1 above was instructive in that the reviewers pointed out the lack of a feedback mechanism in HIF-1α signaling. A natural lack of feedback to the HIF-1α signaling source contributed to diseases such as:
- “age-related macular degeneration
- cancer progression
- chronic kidney disease
- adipose tissue fibrosis
- detrimental effects which are linked to epigenetic changes.”
The point was similar to a study referenced in The PRice “equation” for individually evolving: Which equation describes your life? that:
“Evolution may preferentially mitigate damage to a biological system than reduce the source of this damage.”
This review subject has many interdependencies and timings within a complex network. Contexts are important:
“Cross-talk between NF-κB [nuclear factor kappa B] and HIF-1α in inflammation might be organized in cell type and context-dependent manner.
It seems that ROS [reactive oxygen species] affect HIF-1α signaling in a context-dependent manner.
Hypoxia stimulated expression of KDM3A and KDM4B genes in different cellular contexts. Given that KDM3A and KDM4B are the major histone demethylases which remove repressive H3K9 sites, their role as transcriptional cofactors seems to be important in activation of HIF-1α signaling. Members of KDM4 subfamily have a crucial role in DNA repair systems, although responses seem to be enzyme-specific and appear in a context-dependent manner.
Acute hypoxia can stimulate cell-cycle arrest but does not provoke cellular senescence in all contexts.”
It wasn’t mentioned that hypoxia evokes cellular Adaptations to stress encourage mutations in a DNA area that causes diseases.
The review was tailored for the publishing journal Aging and Disease, and the subject was best summed up by:
“HIF-1α can control cellular fate in adult animals, either stimulating proliferation or triggering cellular senescence, by regulating the expression of different KDMs in a context-dependent manner.”
This review covered hypoxic conditions during human development that are clearly origins of many immediate and later-life diseases. However, cited remedies only addressed symptoms.
That these distant causes can no longer be addressed is a hidden assumption of research and treatment of effects of health problems. Aren’t such assumptions testable here in the current year?
http://www.aginganddisease.org/article/2016/2152-5250/ad-7-2-180.shtml “Hypoxia-Inducible Histone Lysine Demethylases: Impact on the Aging Process and Age-Related Diseases”
2 thoughts on “Lack of oxygen’s epigenetic effects”
your recent piece on hypoxia can you write what you think it means to me? art janov
Hi Dr. Janov! Thanks for challenging me to make the post better.