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Comment by thebeastie | Hacker News Reader

Proponents of fasting will love this, since the idea is that not eating for a while will cause the body to scavenge for this old / damaged cell material.

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And is that nonsense or is there evidence that backs it up?

FYI: https://www.nih.gov/news-events/nih-research-matters/fasting...

But as to the mechanism... not a scooby.

> Long periods of fasting between meals helped male mice live longer and healthier lives, regardless of the content of their diets. More studies are needed to confirm these results and understand how different fasting periods may impact health.

I am sure fasting proponents promise way too many things, but the underlying cell cleanup mechanism [0] is very real and received the Nobel Prize in 2016 [1]

[0] https://en.wikipedia.org/wiki/Autophagy

[1] https://pubmed.ncbi.nlm.nih.gov/27912049/

The wiki page does not mention fasting.

> fasting and CR [calorie restriction] are the most potent non-genetic autophagy stimulators, and lack the undesirable side effects associated with alternative interventions.

> We conclude that both fasting and CR have a role in the upregulation of autophagy, the evidence overwhelmingly suggesting that autophagy is induced in a wide variety of tissues and organs in response to food deprivation

From: https://pubmed.ncbi.nlm.nih.gov/30172870/

I have multiple relatives who are aging researchers.

Fasting is healthy and normal. Many humans historically regularly "fasted" by today's standards just by going 12+ hours between modest meals.

We know that it slows signs of aging, but it can also depress the immune system (which might be why it slows aging), so it can still cause you to die young.

The effects of fasting on all-cause mortality are generally positive, but it's unclear right now whether that means people need to do uncomfortable levels of fasting or if most of us are just killing ourselves with eating too much and too often.

But here we want cells to eat themselves, not damaged organelles. I believe nuclear DNA isn't among the things cleaned up by autophagy.

> I believe nuclear DNA isn't among the things cleaned up by autophagy.

The ProNukes have gone too far this time.

Spermidine does this as well.

https://www.tandfonline.com/doi/full/10.1080/15548627.2018.1...

If you want to know how to increase it ask me how.

> Dietary spermidine is rapidly resorbed from the intestine and distributed in the body without degradation [37].

Not only by diet, we make spermidine endogenously.

https://www.researchgate.net/profile/Wesley-Brooks-2/publica...

B6 will increase ODC and AMD1 activity.

B2 for SMOX and PAO.

This will keep this pathyway functioning well.

> If you want to know how to increase it ask me how.

how?

Thanks for asking! The polyamines, including Spermidine, are created off of the urea cycle and increasing the urea cycle is dependent on lowering, or inhibiting Nitric Oxide Synthase. There are plenty of natural NOS inhibitors, like Black Tea and Ginger. This will mean instant of Arginine going to make Nitric Oxide it is instead shunted to the enzyme Arginase in the urea cycle. Arginase needs Manganese too increase function, so maybe mussels will help here since they are very high in manganese.

But we cannot stop here since this might just mean that you spin the urea cycle around and around. What we need to do is stimulate Orniothine Decarboxylase (ODC) to pull the ornithine out of the urea cycle to the polymaine pathway. ODC need B6 as a cofactor to increase activity so taking B6 or eating foods high in B6 will do well here.

Not that we have the ornithine going where it need we need to make sure we can turn it into spermidine by making sure we have enough of the coenzymes for those enzymes. The coenzyme here is SAMe.

And that's it. But be careful, because if you have messed up genetics like me you already make enough spermidine and it will cause great mental turmoil, even suicidal thoughts.

Here is the pathway: https://www.science.org/cms/10.1126/science.aan2788/asset/5e...

On mental illness and spermidine: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293545/

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