Thread by @Jopo_dr

I went to med school to be a medical geneticist (went off piste) but always been fascinated by it. One way the environment interacts with our genome is through methylation - the addition of methyl groups to certain points in the dna string

This physical/chemical manipulation changes how the dna string folds and how easy it is for transcription machinery to access it. We have the same genome as ourselves as an egg, but clearly have organs and limbs now - methylation helped the egg produce these changes

An ENT surgeon friend sent me this epigenetic study on Japanese centenarians - they show less age related methylation at expected genes such as cancer and neuropsychiatric but the surprise was they are undermethylated for anti inflammatory genes eg TGFb

thelancet.com/journals/lanhl…

I found this interesting for four reasons 1) in med school I remember aspirin randomly decreasing bowel cancer rates - could it alter methylation? (It does) …lepigeneticsjournal.biomedcentral.com/articles/10.11…

2) my hypothesis would be stress is a profound methylator- psychological or biological, so I looked at early and mid life stress methylation pubmed.ncbi.nlm.nih.gov/29943663/

I think it was already somewhat known that maternal mothering and grooming can permanently affect infant mice stress responses (mice are not human though and methylation varies with species) but the phenotype is seen in humans

For example injured soldiers with and without PTSD have different rates of age related diseases such as T2DM and arterial elasticity, coronary artery disease

Interestingly in the mice the social defeat stress (arguably probably nhs workers?!) changes an area in the X chromosome which suggests an inter generational hereditary component to parental stress

Anyway 3) biological stress. We have all long observed there is chronological and biological age. The latter seems related to genes, deprivation, alcohol or substance use, stress etc…and INTENSIVE CARE (of course these patients probably pre select the above issues often)

A near death experience has biological and psychological effects on people. My experience at an ICU follow up clinic kind of humbled me with respect to the effect that delirium had and has on their lives.

They have ongoing memory deficits, cognitive processing disorders, high rates of trauma and even suicide. Many aren’t back at work 1 year later :( We don’t magically “fix” people.

Delirium obviously relates to mortality biologically too because they can’t comply with optimal medicine/lines/drugs and the inflammatory axis is out of kilter - brain does have an immune system after all (microglia) and the hippocampus is damaged by cortisol

I looked up dna methylation in icu survivors and it’s quite recently studied - not a lot but there is some skeletal muscle stuff which surprise surprise has different methylation ncbi.nlm.nih.gov/pmc/articles/P…

A slight tangent is the effect of metabolism in the sense things called sirtuins which are influenced by fed:fasting cell states alter epigenetic patterns - a potential long term interaction from icu feeding and hyperglycaemia

Anyway 4) if critical illness or major inflammatory responses are linked to longevity and altered methylation are there therapies we should be delivering along side life support to protect the integrity of the genome? (Not vitamin C 🥸) #FOAMed #criticalcare #icu