The mitochondrial NAD+ transporter SLC25A51 is a fasting-induced gene

https://www.metabolismjournal.com/article/S0026-0495(22)00153-6/fulltext

by bilsbie • 4 years ago

106 58 4 years ago

metabolismjournal.com

aesthesia• 4 years ago

In mice, of course. What are the broader implications of this supposed to be?

thornjm• 4 years ago

Fatty liver and high fat in blood is a disease and a risk factor for serious disease respectively.

This study appears to show that fasting is related to inducing the gene Slc25a51 and improving those factors.

I guess this contributes to the body of science around the potential health benefits of fasting.

mistrial9• 4 years ago

ok - but the purpose of publicly identifying by name, a particular genetic component, is to own that function commercially somehow - am i wrong?

aydyn• 4 years ago

Mice are physiologically small humans with tails and fur. Findings in mice are very relevant to humans.

jjallen• 4 years ago

I’ve always wondered what percentage of mice (and other non human animal) findings turned out to be applicable to humans as well.

Anyone have an idea?

Symmetry• 4 years ago

For many things yes. But humans have been under much more intense selective pressure for longer lifespans so easy interventions along those lines that work in mice have a history of not panning out in humans.

alwillis• 4 years ago

One possibly obvious one:

Fasting in mice turns on SIRT3 which requires NAD+ and this newly discovered gene SLC25A51 is involved in transporting NAD+ to SIRT3. There's plenty of data that shows mice can live 30% longer when calorie-restricted due to sirtuins being activated..

Anyone who's ever listed to Dr. David Sinclair speak about longevity, he almost always talks about how NAD+ is possibly the most important chemical in the human body, since we'd be "dead in 30 seconds" without it.

Sirtuins are the longevity genes that are activated when organisms are under duress, which can be simulated by fasting. Your body doesn't know when you're going to eat again, so the sirtuins get activated.

I wouldn't be surprised if researchers and labs are looking for ways to activate SLC25A51 chemically to get the NAD+ flowing to SIRT3 without requiring fasting.

You can listen to David Sinclair and Rhonda Patrick get into the details of how all of this works: https://www.foundmyfitness.com/episodes/david-sinclair

ChrstnBonanno• 4 years ago

Polymorphisms in SLC25A51 might be linked to chronic fatigue or other mitochondria disorders. So that is pretty important.

Sinclair, IMHO, is all protein and zero enzyme and that is his problem. Without enough zinc NMNAT will not function and will slow the SIRT cycle. And increasing SIRT activity by shoving NAD in the cell with out zinc will end up depleting zinc.

TedDoesntTalk2• 4 years ago

Rhonda Patrick is amazing. Been a subscriber to her posts podcast for 3 years. But she has tons of free content on YouTube and elsewhere.

It was disappointing to hear David Sinclair makes his own resveratrol… can’t get it

rsync2• 4 years ago

"I wouldn't be surprised if researchers and labs are looking for ways to activate SLC25A51 chemically to get the NAD+ flowing to SIRT3 without requiring fasting."

To what end ?

Fasting would be cheaper, easier and less time-consuming and would include all of the related, broad-spectrum effects that we also believe fasting may produce.

I guess if you're a pharma investor or existing, entrenched player it makes sense to go that direction.

As a consumer, however, I wonder why (pills that might convey a subset of the benefits of fasting) would be interesting in any way.

caeril2• 4 years ago

Why does this tired argument always appear on HN?

We share 97% of our genes with mice. Our organ systems and metabolic pathways are extremely similar. Our homeostatic mechanisms are nearly identical.

Some mouse models don't carry over to us, to be sure. But the reality is that most do. Do we know for a fact that this paper applies to us? No. But it significantly updates our priors. And that's always noteworthy.

d0mine• 4 years ago

9 out 10 results in mice do not transfer to humans.

For example, fasting for several hours in mice and in humans are completely different things (a human would have to fast for days to get similar results).

Iwan-Zotow• 4 years ago

Would it help with treating anorexia?

ck2• 4 years ago

Paper is fascinating to the right interests but oddly extremely specific for HN?

Do some people just not have Slc25a51? Does this matter?

Is this supposed to be some kind of longevity insight?

pizzathyme• 4 years ago

I am also a long time hacker news reader and even a longevity and biology enthusiast, and I can confirm that I also have no idea what any of this means or why it is on the front page

maerF0x02• 4 years ago

I think this is relevant to the biohacker crowd and much of the NAD+ (and NMN) interested crowd (such as followers of David Sinclair or David Attia), and topics around the Yamanaka factors & Hormesis induced from existential threats (such as heat/cold or fasting, or fasting mimicking things like metformin inducing low blood glucose in otherwise healthy people)

I'm not a doctor or a researcher etc. Just a guy who likes to watch these things play out and barely understands what I hear :)

kbouck• 4 years ago

David Attia

Did you mean Peter Attia?

zahma• 4 years ago

NAD+/NADH is kind of an important energy transporter molecule in your body. If you do not have NAD+ to be reduced to NADH, your body cannot oxidize NADH to power the electron transport chain and drive forward ATP synthase.

In other words, you will die literally from exhaustion.

adrian_b• 4 years ago

And humans and the other animals make these substances from the various forms of vitamin B3, e.g. niacin or nicotinamide, which must be provided by the food.

Insufficient intake of this vitamin causes the disease named pellagra (which was frequent at people who ate almost only corn, i.e. maize, with too little of other vegetable or animal food).

upsidesinclude4• 4 years ago

NAD & NMN are recent developments in the world of supplements. Read about them a bit, they are natural compounds in the body. Over time our ability to generate them decreases. Each can have profound effect on things like muscle & tissue repair or lifespan.

This is effectively stating the mechanism for utilizing these is shown to be linked to fasting.

The efficacies are already proven. A new study which accounts for the activation of the gene and utilization of the supplements will likely show a major therapeutic potential or life extension therapy

ramraj072• 4 years ago

Citations please?

Here’s a snippet from WebMD:

While there is some evidence that suggests NADH supplements might reduce blood pressure, lower cholesterol, help chronic fatigue syndrome by providing energy, and increase nerve signals for people with Parkinson's disease, there isn't enough information to know for sure how or if these supplements work.

threeseed• 4 years ago

This is one of the companies that sells NAD supplements: https://www.elysiumhealth.com

I can't speak to any of their claims but the company is legitimate.

upsidesinclude4• 4 years ago

WebMD is not a great resource when it comes to new medicine or even old medicine for that matter, I digress...

Found this on the first Google search: https://www.nmn.com/topic

Are they selling something, sure, but the studies are all linked.

The wide research interest alone should be some indication of the promise these compounds hold

Steve446• 4 years ago

My wife was recently diagnosed with metabolic myopathy and they ( NHS in the UK) are currently trying to identify what actual problem is; so far it's something to do with ATP and Phosphates affecting how the muscles convert fuel into energy I believe.

My chemistry and biology knowledge are fairly limited, but I di like to understand things and so started looking into this and found [1]. For my level of knowledge I feel it gave a great balance between what I could understand whilst also showing how incredibly complex human chemistry is.

There is currently a related discussion here in "A physical wiring diagram for the human immune system" / https://news.ycombinator.com/item?id=32381790 but the link to biochemical-pathways.com is way over my head.

I found that BBC link useful and thought others may do as it's related but simple.

[1] https://www.bbc.co.uk/bitesize/guides/z2vbb9q/revision/1

Madmallard3• 4 years ago

How did they even get to that point to diagnose that?

I suspect taking ciprofloxacin 8 years ago caused metabolic myopathy in me as well because of its known deleterious effects on mtdna and oxidative stress well established in research, but doctors have never been helpful at even going in that direction. I had a loss of 35% VO2 max in the first year alone afterward.

Steve446• 4 years ago

She was being treated for osteoporosis but as that was settling down her muscle spasms were getting worse. We had assumed they were related to the osteoporosis and so hadn't discussed much about them until the bones had 'healed', the endocrinologist wasn't that aware that they were becoming a problem. She started looking into Hyperparathyroidism as a possibly cause.

As that was progressing slowly we went privately to see a consultant neurologist; he examined her and looking at things like jaw strength concluded it was metabolic myopathy related to a problem with the muscle cells and phosphate. He said he'd only seen it a couple of times before and it's very rare and not surprising it hadn't been picked up earlier. We're now going in for muscle tests, DNA tests, and all sorts to try and identify what is wrong and how/if it can be fixed.

The thought is her osteoporosis was likely caused by the cells leaching nutrients from the bones as they couldn't get them normally, that has been stabilised by traditional Alendronic acid, calcium, and Vit.D.

caeril2• 4 years ago

but doctors have never been helpful at even going in that direction

Yeah it's really weird that when doctors profit from pathologically over-prescribing antibiotics, they're hesitant to consider the long term effects of doing so.

It's almost as if "It is difficult to get a man to understand something, when his salary depends on his not understanding it".

Really, really strange.

thesaintlives• 4 years ago

I can't really comment on the article but I can comment on taking a NAD supplement. I take NAD every day and magnesium L threonate every few days (whenever I feel like a need a mental boost). The NAD really makes me feel better. I have no idea what it does but when I don't take it I have more difficulty getting up early in the morning. NAD, magnesium and zinc. Those are my basic supplements and I always take them. Give it a go!

mzmoen• 4 years ago

What brand do you take?

zamalek2• 4 years ago

NAD supplementation is a contested area of research, and there are many studies showing that it doesn't achieve anything useful. Further, NAD supplementation puts stress on the methylation cycle and given that you have a 10-25% chance of an MTHFR mutation (depending on your demographic) you should be very careful with NAD supplementation.

motive• 4 years ago

Can you elaborate on the MTHFR mutation? I did supplementation in the past with similar results to the above commenter.

valarauko• 4 years ago

MTHFR mutation

I'm a geneticist and I still read that as a curse word ...

The mitochondrial NAD+ transporter SLC25A51 is a fasting-induced gene

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