[-SB-]

So - I haven't any further questions - all problems solved - nothing much more to do until people wake up. The entire biomedical push (find gene -> find drug) is nonsense - we require a psychosocial change to alleviate disease not a biomedical approach to ensuring human health.

[-SB-]

--- SUMMARY/CONCLUSION/END-POINT ---

All that you need to know is that everything will be OK if people can simply understand that the mind is designed to know right from wrong objectively/correctly/rationally - and although it's harder than it might be, it's not too difficult.

I'm not entirely sure it was worth the effort of losing the last 20 years of life online to tens of thousands of posts as SB_UK on:
[[1]]http://www.addforums.com/forums/index.php - Forum (mental health)
[[2]]http://www.toequest.com/forum/ - Forum (Theory of Everything)
[[3]]http://richarddawkins.net/forum/ - Forum (Philosophy)
[[4]]http://www.guardian.co.uk/users/sbuk - Forum (Current events)
[[5]]http://disqus.com/SB_UK/ (The Telegraph and Independent newspapers)
[[6]]http://www.thenakedscientists.com/forum/ - Forum (Science)
[[7]]https://www.facebook.com/sumit.acharyya.73 - Forum (Political activism with TVP/TZM and SPGB/WSM)
Note anonymity - this isn't my name.
[[8]]https://www.longecity.org/forum/ - Forum (Healthy Ageing)
[[9]]http://seqanswers.com/forums/ - Forum (Molecular Medicine)
[[10]]https://www.facebook.com/groups/cambridgeclt/ - Forum (Sustainable living)

So - if the species understands ToE [[2]] and thereby generates a mind (/ie/ wisdom where the wise mind is the mind of scientist [[6]] /ie/ the two terms are synonymous if they're to be used correctly) which understands its own context (/ie/ how evolution works) - then the species settles into social structure formation /ie/ into an actual social species [[3]] through simple communication of the idea (generalized Theory of Everything or mechanism of God / Love) [[10]]. The transition from love of learning/money to love of learning which then occurs with social species formation (/ie/ an actual change in motivation from love of money/power to love of learning) - corrects the dysfunction which we see in the psychiatric spectrum of the informationally sensitive [[1]] being bombarded by excess information (google 'SB_UK SEN EMP SYS' for more). An actual social species just won't suffer the problems which're described in the newspaper [[4,5]]. Problems will have been prevented. Through social species formation (species-wide enlightenment) there will be a change in appetite/preference towards a healthy life-style including towards sustainable living, towards equality of man [[7]] and towards a certain food intake and exercise profile which will give rise to an underlying physiological change which'll ensure healthy ageing [[8]]. As a consequence of all of this /ie/ preventing problems (notably including the diseases of Western (now global) living) - we do not need to apply the biomedical approach of 'cure' [[9]] though may still use molecular genetics to validate health promoting interventions. So - to use molecular genetics to define what might make us **super** healthy (the optimal profile of life) as opposed to how to reverse sickness (when it's too late /eg/ when your teeth have fallen out from decay, regeneration is not possible).

These ideas rely heavily on the science of pattern/nature of maths (why Maths works), the Theory of Everything (Physics), ketone (Chemistry), mitochondrial biogenesis (Biology) and information recognition (Psychology). I'm emphasizing the sciences as the transition we're in the middle of might be seen as a Science -> Art transition in that the crowing glory of Science is species-wide enlightenment. 'Science' will continue afterwards - but not to explain how reality works, more so in helping us generate technologies which improve the collective experience of life.

[-SB-]

Great post. Thank you for the links

No - thank you for reading.

Love NGS - one day we'll get to use it for defining the lifestyle changes to supraphysiological state - and then - we'll be there.

A happy healthy species.

[michealsclark]

Great post. Thank you for the links

[-SB-]

If I were to describe where I'm at.

[Q1] I would need some evidence on what the ideal FASTing regime is (? 4 days each week ?)
[Q2] And whether it's best to remain in ketosis for life or [Q2b] whether we should drop out from time to time.

The ridiculously over-sized A3 page above is the experiment I'd need to attempt.

NGS can be used to define how to make human beings better than normal - rather than how to study frank pathophysiological states.
If we're supra-normal - of course the issue of disease won't come up.

Why do I think it might be good to step out of ketosis occasionally ie ? a monthly feast of :-) ... ... wait for it ... ... bread!! - just wondering whether the dedifferentiation into stem cells need be redifferentiated in an IIS environment ie that we need engage IIS with a few slices of bread - drop out of ketosis and re-instate any cells we've removed.

Just to illustrate how we're about to see a change in direction in medical research - take a look at Weissenbach - helped to generate our original maps of the genome - and has now shifted in true French style into studying the effects of diet on the gut biome where ... ... ... Partridge has shifted things on yet further.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988561/

-*-

What's the problem we're having ? The world's medical researchers don't want to offer the conclusion (as described in this thread) - because they're worried that they'll then be out of a job.
Now - for the record - all people will be out of a job.
And for the record medical researchers SHOULD fear unemployment - a training in medical research doesn't get you a job on the outside - perceived as too highly qualified to take ANY job.

Who's interested in sequence data outside of us ? Nobody.

[-SB-]

The problem is that we're looking at a NAND model.

NOT one network [FED IIS]
AND other network [FASTed ToR]

-- and so it's obvious that no drug can work - somehow the drug needs to switch off not one but a network of genes - and then switch on not one but another network of genes.

I'm afraid the somewhat appropriate phrase is - 'you can't have your cake and eat it' ... ... ... there's no way of inducing autophagy in the FED state.

[-SB-]

Thing is - that we all love epigenetics (particularly the CEGX contribution) or the dinky little machines coming out from Illumina, yes microarrays are pretty - and you can't beat a lovely biome study ... ... CRISPr provides us with a theoretically infinite capacity to generate data ... .. and the current drive towards dedifferentiation/differentiation in stem cells is wonderful too - but we now know all of the answers (we knew this day would come) if we'd just choose to put everything that we've accumulated to date together.

Simply - there's a process of autophagy which clears disease.
Being worked up in Oxford and Cambridge by Yun Zhang and David Rubinsztein, respectively.
All that's required is to study the biology of FASTing.
Valter Longo (Longevity Institute) has based his career on this idea.

Now ... ... simplifying into one line (all of the above techniques we love) and just to illustrate.

FED -> IIS network gene expression -> fixed in place through epigenetic modification -> altered biome (low diversity) -> disease (damage accumulation)
CEGX are working up the transition from one network being switched on to the other network being switched on ie the way that the 'switch' works or methylation -> removal of methylation.
FASTED -> ToR network gene expression -> fixed in place through epigenetic modification -> altered biome (diversity) -> health (via stem cell reactivation replenishment of damaged cells/components)

[-SB-]

Great post I would like to thank you.

:-)

Love science - and there's going to have to be a realization at some point - that we've stumbled upon the right answer.

There are 2 metabolic biochemical states (in effect 'FED' (high GI carb + protein or the Ins/IGF-1 promoting state) and 'FASTED' states (recapitulated through a certain profile of low GI veggie and certain types of oil)).

The right answer being a preventative scheme which'll eradicate disease. And that we're too complicated to 'fix' or 'cure' disease.
I'm sure there're a good few people on this forum that're going insane with the level of complexity that's found when we combine all of our current ultra-high throughput tools.

It was bad enough 30 years ago - but now we're drowning in data - and it's a relief that we've sufficient evidence in the background to suggest that there's another way around - a way that will work.

I've tried the idea out in real life with many scientists - all agree - but none can do anything because it's the opposite paradigm to the one which pays the bills.

I've continued this thread on the longecity forum - as the idea runs in parallel with the only proven mechanism for extending longevity in every eukaryotic model studied to date.

ps thread copied here also

http://www.addforums.com/forums/showthread.php?t=194392&fbclid=IwAR1v8c-ZIBeZT61d3O97h5gJJiE4MWWbqzuu8Y3Kd2DnEUDcVFaNluuumBw

-*-

pps Just looked at the first post - and I think Illumina have bought PacBio since - they've obviously spotted the problem.

[mysentimentsexactly]

Great post I would like to thank you.

[-SB-]

... ... Continuing ... ...

The Importance of (NGS in) longevity research

https://www.longecity.org/forum/topic/102584-importance-of-longevity-research-powerpoint/

[-SB-]

That particular moment when one realises that other people do know.

Oxford University waiting in the wings.

So far, abnormal autophagy has been reported to have association with the pathogenesis of coronary artery disease, neurodegenerative diseases, Type II diabetes, cancer and ageing.

The basis to human health is really ever so simple.

2 networks - mutually exclusive - FED and FASTED.

FASTED clears the damage set in FED state.

[-SB-]

And the 2018 Nobel prize in chemistry goes to ... ... ...

--- example --- Imagine if TNFa (the current #1 selling drug is anti-TNFa) is essential for infectious disease clearance, tumour surveillance in 'FASTED' state ie is essential for health in the 'FASTED' state and we introduce an inhibitor for it - we're destroying our own capacity to 'clean' ourselves.

ooopsy !

Bicycle (4) Therapeutics

We recently identified physical exercise as a newly defined inducer of autophagy in vivo.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463459/

NF-κB Activation Represses Tumor Necrosis Factor-α-induced Autophagy

http://www.jbc.org/content/281/41/30373

[-SB-]

Ruby on autophagy.

https://www.bbc.co.uk/news/health-44005092

- the idea in this thread is of such great importance.

The interest which lead to NGS emerging is based around the money it was hoped would be made through diagnostics and therapeutics.
Pharma dreaming of blockbusters to power their exec's lavish lifestyles.

The idea put forwards in this thread squarely rejects the idea of both Dx and Rx and suggests that lifestyle change is absolutely required for human health ... ... that is - that we've 2 mutually exclusive Systems Networks ... ... therefore only natural and not artificial intervention can work to switch us from one into the other.

This idea (ie need to have a very large number of susceptibility loci) was the basis to the statistical model of the quantitative trait exactly 100 years ago.

An infinite (large) number of loci each contributing either a positive (+1) or a negative (-1) effect on a quantitative trait. Arrange all loci randomly to Hardy Weinberg Equilibrium and a quantitative trait results. So ... ... an infinite (large) number of loci giving rise to quantitative variation in any given trait.

Fisher’s article (1918)[1] and its easier to understand summary [2] are landmark papers that founded the field of quantitative genetics, or in modern parlance, complex trait genetics.
[Their purpose] to derive the theory of the resemblance between relatives due to their genetic covariance at 1, 2 and many loci

https://academic.oup.com/ije/advance...dyx129/3977804

Happy 100th birthday pretty much today (early October 1918).

http://www.indiana.edu/~curtweb/L567...Fisher1918.pdf

A very big deal - perhaps the most important publication in genetics ? alongside Galton's & Mendel's publications both from 1868.

Oh my ... ... Happy 150 years of age to these papers also !

The idea in this thread vindicates Fisher at least in the sense that the complex trait arises through whole genome-wide distribution; there're no key loci - and the solution to the problem (of disease) - arises through embracing the existence of 2 system-wide networks and living one's life accordingly.

Lots of articles on accessing autophagy/apoptosis on the internet.
eg https://greatist.com/live/autophagy-fasting-exercise

Is there an easier way ?
Nah. But there’s a lot money to be made if researchers can distill the benefits of autophagy into a pill, so you can be sure they’re trying.

If we strengthen physiological resilience - we never actually acquire disease - hence diagnostics/therapeutics are no longer required.

As the research proposal above suggests - we can reinvent NGS as a measure of how frightfully healthy we are ... ... which'd be nice to know.
At least to validate interventions - is 15 mins HIIT (FASTed state) as good as an hour run (FASTed state) ?
But as far as disease research - well - we have the solution to disease now.

What we needed was the realization that we absolutely need to make lifestyle changes ... that the combination of detection / therapeutic can not work - such that we'd make the necessary changes to make disease a thing of the past.

Bye bye disease hello ever increasing health - as measured by NGS.

[-SB-]

Thanks for the links!

:-)

A zillion other links if you like.

It's what happens when you're bored out of your skull in the usual lab meeting watching people infer the Universe from failed Western blots.

When we started all of this - we had thought that disease genes 'd fall out of the genome. Didn't happen. And because where 'if all you have is a hammer ... ... ...' meets 'the definition of insanity is doing the same thing over and over and ... ... ...' - this sort of 'science' happens - I think it was announced yesterday.

https://www.genomicsengland.co.uk/matt-hancock-announces-5-million-genomes-within-five-years/

Ironically, the genomics revolution was sold as the silver bullet towards identifying targets for intervention - it has (instead!) identified just how very complicated human beings are.
The complexity is impressive - however we need not focus on the complexity - simply the existence of 2 tracks - cellular damage accumulation and cellular damage clearance.

The science of assessing health improvement rather than microscopic analysis of the disease state; if we focus on health improvement - then the disease state never will arise.

The solution to disease arises through making the connection between biochemistry and genetics through metabolic profile arising as a consequence of lifestyle (essentially quantity and quality of food, exercise and moral/social functioning) choices.

[luc]

Thanks for the links!