View Full Version : DNA methylomes of newborns vs centenarians


SB_UK
10-05-13, 04:27 AM
continued from here ... ...

http://www.addforums.com/forums/showthread.php?p=1549319&posted=1#post1549319

SB_UK
10-05-13, 04:39 AM
http://www.pnas.org/content/109/26/10522.long

The unmasked DNA methylation landscape shows that DNA obtained from a 103-y-old donor was more unmethylated overall than DNA from the same cell type obtained from a neonate. So - the major mechanism of epigenetics is really simple to understand in overview.

http://en.wikipedia.org/wiki/Epigenetics#DNA_methylation_and_chromatin_remodeli ng
It's divided into either DNA modification or histone modification ie sticking a little bit eg methyl group onto DNA or sticking a little bit eg acetyl group onto a histone.

The histone is the (lesser known + charged counterpart/) binding partner (stabilizes) (negatively charged) DNA.

-*-

So - we've general 'loss' of methylation of DNA in ageing (see PNAS paper above).
And - we've a beautiful parallel in:
http://en.wikipedia.org/wiki/Histone_deacetylase_inhibitor

- or the prevention of loss of acetyl groups in eg cancer prevention (which is, in turn - related (ie cancer incidence) to ageing).

-*-

Simple explanation :

We've these eg methyl-DNA, acetyl-histone epigenetic modifications which 'protect' our genome
- and with ageing - they're stripped.

We can think of them as a protective shield eg in Star Trek where Kirk is forever being told that the shields are at 50%, 20% under Romulan bombardment - and that 'hull breach' (DNA exposed to harm) will occur in 60 seconds ... ...

As they're stripped (these small carbon chain shields of our DNA and histones) our genomes are exposed ... ... and when they're fully exposed
- our mortal coil fails.

-*-

Obvious question
- how do we prevent carbon chain modifications to DNA/histones from 'falling off'.

eg increased vulnerability to oxidative stress and a decreased capacity for methylation
How do we prevent oxidative stress ?


In the UK, there's a major initiative to discover the basis to healty ageing (supported by the BBSRC) (http://www.bbsrc.ac.uk/funding/priorities/bbuh-ageing.aspx)
- it's the only consideration which medical/biological research should be holding -

- where we know the basis to healthy ageing.

It's simply stress elimination through the generation of a fair society (as proven by medical and social epidemiologists Marmot, Wilkinson and Pickett)

- where stress operates through cortisol
- cortisol exerts itself by driving oxidative damage
eg paper reference (http://www.ncbi.nlm.nih.gov/pubmed/23490070) <- just read first sentence
and
eg paper reference (http://www.ncbi.nlm.nih.gov/pubmed/23989608) <- just read title and sentence beginning 'Mechanistically ... ... ...'
(chronic) oxidative damage leads to premature ageing.

SB_UK
10-05-13, 04:50 AM
What's the solution ?

Love is all you need.

Explain what that means ?

Development of the social reward system (at the level of the anterior cingulate gyrus)
- development of the mirror neurone system / development of empathic capacity
- such that the mirror neurones of the reward system

ie neurochemical reward from 'giving rather than receiving'

- is in full swing

... ... whereby - you love your neighbour

- with a mind which is rationally/morally construed in a manner that you'll support/actively drive social change
- to generate a fair societal infrastructure

- one which does not stress out your fellow man.

Resulting in the alleviation of suffering (with disease eg disease of Western living being a subset/end-point of suffering).

-- Game Over --

SB_UK
10-05-13, 04:56 AM
Can't see the wood for the trees
- you don't need to know what each and every modification of DNA and histone does

- we need to see that the gradual loss of small chain aliphatic modifications results in exposure of the genome to 'harm' - and so we have to delay the process (eliminate oxidative stress).

Where - I think the mechanism is something as simple as these small chain modifications assisting 'condensation' (ie tight coiling) of histone and DNA
- and that removal of these DNA/histone modifications
- simply results in unravelling of the complex ie

|| = DNA
()() = histone

from

(|)(|)
to
|()()|<- EXPOSED

- thereby exposing DNA (the genome itself) to harms way (oxidative free radicals)

- where we know (eg 2 hit hypothesis) - that only 2 strategic hits in the genome can turn a cell into a cancer.

IE - we're exposing DNA through epigenome stripping to mutagenesis from chronic oxidative stress through (particularly) (di)stress exposure in an unequal (global) society
- supported by the systems of money and law.

SB_UK
10-05-13, 05:04 AM
Love your neighbor as yourself

... ... ... but you gotta' know how ... ... ...

a personal enquiry into / and real world application of morality.

SB_UK
10-05-13, 05:12 AM
Oxygen is a violently reactive molecule - we need to protect ourselves by optimising aerobic metabolism.

This requires a rock steady blood glucose level.

Cortisol (stress) drives massive fluctuation in blood glucose levels.

Since cortisol leads to oxidative damage
- we can infer that it's (through blood glucose variation) resulting in unmanageable stress to the mitochondria.

The single major cause of stress which we're subject to
- is the stress of living with a hierarchical society for access to the basic essentials for survival.

Make basic essentials available to all people for free
- by their own efforts
- and we'll solve the fundamental causal problem on human suffering overnight.

It's happening:
http://www.transitioncambridge.org/thewiki/wiki-uploads/TTEDAP.HomePage/Vision2030.pdf

Now to ensure that it happens by Sunday week.

ADDers don't wait.

SB_UK
10-05-13, 05:13 AM
23 Haikus
We conclude this visioning document with eleven haikus (short Japanese poems) that describe
some of the first things that came to mind when we envisioned Cambridge in 2030. The authors
have kindly given permission for them to be published here.

I cycle to work
to teach others to cycle
no cars go past me

Home-made energy
Slow convivial supper
Nourishes the soul

We value our resources
Cuba is our inspiration
Growing and sharing our food

No food is processed
We share in preparing it
We know what we eat

Family near by
close community will help
whatever you need

Silence. A quiet breeze
Sounds of people and nature
Gone oil powered transport

Helping my neighbours
in gardens where cars once were
time free and unfixed

Local fruit and veg
Grown in small well-tended fields
All I can buy now

Footpaths are wending
where once concrete scarred the earth
the roads are blooming

Working actively at all ages
Dog sleeping in the road by night <- as long as they've been potty trained
children playing in the street by day

Farming in the Fen
Silence is all around us
the world is so peaceful.

SB_UK
10-05-13, 05:19 AM
But my dog wants to sleep next to me ... ... ... ?

It's a minor quibble.

Cats however are considerably more adventurous.