Tuesday, January 21, 2020

Barja, an aside

I quite enjoyed Barja's review

The Cell Ageing Regulatory System (CARS)

but found this section a little uncomfortable:







Hmmmmmm. Plant based, healthy fruit and vegetables, bad animal fats. Not my sort of outlook really.

In another of his publications here

Highly resistant macromolecular components and low rate of
generation of endogenous damage: Two key traits of longevity

there is this comment

"It was also found that 6–7 weeks of dietary restriction are enough to decrease MitROS production and 8-oxodG in mtDNA and nDNA in rat liver (Gredilla et al., 2001a )".

Gredialla et al (incl Barja) 2001a is

Effect of short-term caloric restriction on H2O2 production and oxidative DNA damage in rat liver mitochondria and location of the free radical source

Here they found, by eyeball, an approximately 50% reduction of in 8-oxodG in mitochondrial DNA after those six weeks of quite severe caloric restriction:























Now let's compare this with the degree of damage reduction (this time using the term 8-OHdG as the marker rather than oxo-8dG, which appears to be the same thing).

Here's the change in mtDNA damage marker in brain mitochondria using F3666, one of the worst ketogenic diets around:























Just by eyeball I make the drop in mtDNA damage out to be greater than 50% by two days and something like 75% by three weeks. On ad-lib food consumption. No hunger.

Considering that F3666 does not extend longevity in mice (it doesn't shorten lifespan either, despite causing liver damage and it does actually improve health during ageing in rodents) this does, for me, slightly knock some of Barjas core ideas.

Sad but true.

Peter

7 comments:

  1. Spouting the vegan mantra might help keep grant money flowing - but sort of means he hasn't seen papers like:

    http://www.plosone.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pone.0088278&representation=PDF

    or the Epic oxford papers - there are also some Japanese papers that found correlative dangers in vegan diets..

    The vegan meme is a popular ungrounded narrative - glad they are leaving more meat and fish for me - buy I worry about their children's brains - growing brains need good fats and the sort of stuff found in meats - kids in the third world with poor vegan diets don't seem to recover even if they get a better diet later.

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  2. Unfortunately, the growing popularity of veganism implies less demand for meat and thus lowered production.

    For instance, here in India, the doctors give hysterical advice about dangers of eating mutton and have lowered the demand significantly. Result is mutton is three times as expensive as chicken.

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  3. What is fatty acid composition of F3666?

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  4. F3666: see Table 1 on page 3 at https://link.springer.com/content/pdf/10.1186%2F1743-7075-2-28.pdf

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  5. @cavenewt:

    https://www.dailywire.com/news/british-scientist-may-have-found-cure-for-cancer-by-accident

    https://www.nature.com/articles/s41590-019-0578-8.epdf?referrer_access_token=kFu_NrWFIkpIHCkKGRnOl9RgN0jAjWel9jnR3ZoTv0NjOoBZR7tEtwlsa1xeSU1tSn9OqKp9tJ7vTk8p7vCmAQ8qq7tpdMDkkCOdHvdAnN49xW6X-XeBi6gqyGM3xYT8dkedMZCypj-TFzhNCGomCoo_SlMlW12mWlhHFh5Mw

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  6. @altavista

    Thanks, I've got the whole article now. It'll be interesting to see if this makes worldwide headlines (I haven't had time to look at the paper yet, to see how exaggerated the dailywire article might be).

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  7. No surprise, I had the same reaction.

    CR only seems to actually work on lab animals fed a crappy diet. I've seen comments that it doesn't work in wild-type mice, and it doesn't work in primates fed a non-crappy diet, as it's never been tried.

    That aside...

    "(this time using the term 8-OHdG as the marker rather than oxo-8dG, which appears to be the same thing)"

    Yes, I think you're right. I wish these scientists could do consistent abbreviations.

    So what would Barja's dietary recommendations look like if he knew this?

    "Linoleic acid hydroperoxides (LOOH) formed 8-oxo-dG at a higher level than H2O2 in guanosine or double-stranded DNA...

    "In a lipid micelle, LOOH markedly produced 8-oxo-dG at a concentration one-tenth of that of H2O2....

    "Employing HepG2 cells after pretreated with glutathione peroxidase inhibitor, LOOH formed 8-oxo-dG more abundantly than H2O2."

    "Lipid peroxides as endogenous oxidants forming 8-oxo-guanosine..."

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933685/

    So by all means replace animal fats with what appears to be the leading exogenous cause of DNA damage. Sigh.

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