9 ms·

A dietary supplement makes old mice youthful, but will it work in people?

160 points by gscott 9y ago

pmoriarty 9y ago
"In the latest advance, biologists reported on Thursday that a molecule already sold by supplement makers (even as scientists scramble to understand it) restored youthfulness to blood vessels in 20-month-old mice, an age comparable to 70 years in people..." So which supplement is it? If it's already sold by supplement makers, have there been any reports of similar effects in people?
- mrfusion 9y ago
  The amazon reviews are pretty positive fwiw .. probably not much.
- ridgeguy 9y ago
  From the article: "The new study, in Cell, found that boosting mice’s levels of the naturally occurring molecule NMN, which humans also have, increased levels of another called NAD+." NMN is nicotinamide mononucleotide, available on Amazon.
- deleted 9y ago
  [deleted]
- kurthr 9y ago
  It's NMN (NICOTINAMIDE MONONUCLEOTIDE) and sold through everyone including Wal-Mart and Amazon. Whether it works... on humans? I don't know and I'm not aware of any (completed) human studies.
- bitL 9y ago
  There was a thread a year or so ago on HN where some people mentioned that they narrowed down their supplements to NMN and something else and were happy about that.
  - zspade 9y ago
    I believe it was NMN and Resveratrol (or Pterostilbene.).
mhuffman 9y ago
A link[1] to the actual research says "Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels." [1] http://www.cell.com/cell/fulltext/S0092-8674(18)30152-1 http://www.cell.com/cell/fulltext/S0092-8674(18)30152-1
1024core 9y ago
The compound in question is nicotinamide mononucleotide (NMN). Back in 2016, Keio university in Japan started a human study on its effects on aging: https://www.keio.ac.jp/en/press-releases/2016/Dec/27/49-19313/ https://www.keio.ac.jp/en/press-releases/2016/Dec/27/49-1931... I haven't heard anything since about what happened to the study.
- trakam 9y ago
  Sounds like a good origin story for Kaiju
- AstralStorm 9y ago
  Exactly nothing. NMN failed exploratory trials multiple times. (Similar to resveratrol.) It is just that the regulations ate not being published due to not being interesting to investors and sponsors. NMN might be useful for people with niacin metabolism issues perhaps.
reasonattlm 9y ago
If you are old enough to remember the hype about resveratrol and sirtuins, that eventually resolved to nothing at all of any great use for human medicine, this is basically the same people singing the same song about roughly the same area of biochemistry. On the face of past events, they can't really be trusted to tell you how great it is and how promising it is, so just read the facts and compare with other studies. About the most one can say about this is that manipulation of NAD+ levels is a better exercise mimetic than manipulation of sirtuins proved to be. What it helps to do is explain some of the underpinnings of studies that show a great deal of muscle loss is secondary aging - i.e. disuse. It also suggests that loss of capillaries is a more important mechanism in sarcopenia than other groups believe to be the case, though I think it very possible that this is secondary to stem cell activity loss. The evidence for stem cell decline to be the primary cause of sarcopenia is very good. [1] There is a faction that thinks capillary loss is important in all tissues. [2] Go look at the studies showing resistance training to be pretty effective in seniors before getting excited about NAD+ boosters. The resistance training is probably cheaper and better. One still has studies such as the one showing that dietary nicotinamide doesn't do a great deal in mice [3] - like sirtuin manipulations, it helps fat mice a little, but is distinctly unimpressive otherwise. Remember that calorie restriction extends life by 40% in mice, but probably five years or less in humans - the effects of all these stress response related mechanisms of metabolic manipulation work through a few overlapping core processes, and scale down with species longevity. That's why I see them as a dead end in comparison to other strategies. [1]: https://www.urmc.rochester.edu/news/story/4788/stem-cells-may-be-the-key-to-staying-strong-in-old-age.aspx https://www.urmc.rochester.edu/news/story/4788/stem-cells-ma... [2]: https://doi.org/10.1159/000477402 https://doi.org/10.1159/000477402 [3]: https://doi.org/10.1016/j.cmet.2018.02.001 https://doi.org/10.1016/j.cmet.2018.02.001
- xcavier 9y ago
  There are quite a few supplements that operate to boost NAD+ levels. The one I take personally is https://www.iherb.com/pr/Thorne-Research-Niacel-250-Nicotinamide-Riboside-60-Veggie-Capsules/69577 https://www.iherb.com/pr/Thorne-Research-Niacel-250-Nicotina... For general background on the science + nutrition approaches, see https://www.selfhacked.com/blog/nad-important-increase/ https://www.selfhacked.com/blog/nad-important-increase/
KaoruAoiShiho 9y ago
I'm not a biologist so here's a dumb question. There's a lot of talk about replicating the study experimentally but do we simply not understand biology well enough to make a theoretical analysis? Basically can we not understand on a fundamental level why it works in mice and why it might or might not work for humans?
- taneq 9y ago
  > do we simply not understand biology well enough to make a theoretical analysis? Correct. We understand bits and pieces of biology but we don't understand the entire system well enough to predict anything with any confidence.
- toolbox 9y ago
  The short answer here is yes. We're constantly working to get more complete models, but surprisingly big effects can come from surprisingly small pieces of the puzzle. We still don't even really understand how Tylenol/Paracetamol/Acetaminophen works! A great example of the gap between our current models and what would be sufficient comes from the COX-2 inhibitors (Vioxx/Celebrex). Ibuprofin (Motrin/Advil) and other NSAIDs modulate both COX-1 and COX-2 receptors in the body to reduce inflammation, but inhibiting COX-1 also causes stomach damage. The early COX-2-specific inhibitors were designed from the ground up using our best models, which were thought to be well-understood. Unfortunately, after several years on the market, it was discovered that this also came with a large increased risk of heart attacks and strokes. The body just has so so many moving pieces, and while we're getting better, it's going to be some time before we are able to base these studies entirely on theory, and when we get there we'll be able to skip the mice entirely!
  - ethbro 9y ago
    As my dad (pathologist) put it, "Nature is a lazy bitch. She'd rather repurpose the same thing 50 times than develop something novel." So add up random biochemical pathway * X million years of evoltion, and one begins to understand the fun of drug discovery and testing. "We know this is the pathway involved in heart disease. We know this chemical compound is effective against that pathway. ... Now why are all our mouse models getting erections?"
wakkaflokka 9y ago
So if one were to try taking NMN as a supplement but had no idea which brands were legitimate, what should they do? Go off Amazon reviews? Recommendations anybody?
- shurth 9y ago
  I use Amazon reviews but I try to stay conscious that sexy labels/marketing influences people. When in doubt, stick with the high quality, no additives, stuff like Thorne.
  - CodeWriter23 9y ago
    Yeah also pay attention to the review dates. I wanted to buy a lightning / audio split cable for my iPhone. I noticed the vendor had 800+ 5 star reviews and none for 1-4 stars. Then I noticed all the reviews had been entered in the previous 3 days. /fakereviews
  - amelius 9y ago
    I read a lot of complaints about counterfeits on Amazon (not this particular product), so I'm avoiding them especially when it comes to food and supplements.
stevenwoo 9y ago
I heard about this on NPR last week - even if it could make old people's blood vessels youthful, it seems like it would be better to just make the person change their diet and their exercise regimen, assuming exercise was possible. This chemical only affected blood vessel health. This is only one component of health. Bone density requires load bearing exercise. Another recent study pointed out lack of exercise led to nerves to major muscle groups fading away with lack of use - led to muscle loss - one has to use those muscles to use the nerves, age related muscle loss can be staved off by exercise of the muscle groups in question.
- themodelplumber 9y ago
  The supplement or the pill has magical abilities though. Many people who will say "I die when I die" when told to diet or exercise will take a pill with no complaints. And as a hobby dieter & big loser: Once you realize diet is something requiring long-term conscientiousness, the truth and enormity of the change can hit very hard. It is an emotional roller coaster that can just as easily make people more fat than when they started.
  - NIL8 9y ago
    "And as a hobby dieter & big loser" - I love this.
  - jack_pp 9y ago
    If they don't care about their own health and longevity I would argue their lives shouldn't be extended against their own will. Should we also give free houses and luxury cars to people who refuse to work?
    - thriftwy 9y ago
      Shoud we sell stuff to people who refuse to work out? The answer is obvious yet you're not seeing it.
    - distances 9y ago
      > Should we also give free houses and luxury cars to people who refuse to work? I know you meant this as a rhetorical question, but yes, I think society should provide free basic housing for those that can't afford it, whatever the reason.
kuwze 9y ago
I think the future of age-related research is going to focus on inflammation. There is already a term for it: Inflamm-aging[0]. [0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963991/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963991/
- reasonattlm 9y ago
  A good recent paper on sources of inflammation in aging: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850851/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850851/ As it points out, the most obvious and promising of current prospects for reducing inflammation is the selective destruction of senescent cells. Though I think that the clearance and recreation of the entire immune system, to remove all of the senescent, exhausted, misconfigured, etc, immune cells is also a promising path, albeit further away from being safe enough to apply to old people.
Empact 9y ago
This article prompted me to research and write a plea for my friends to take this supplement (I've been on it for a few months, before that took Nicotinamide Riboside, NMN's precursor): Please consider taking NMN for health and longevity. Nicotinamide Mononucleotide (NMN) is a direct precursor of NAD+ which broadly activates/energizes the Sirtuin pathways. Previous interventions either activated only one of these pathways[1] or activated them less effectively[2]. Why all the fuss about Sirtuin pathways? Well, it makes sense that your body would have a built-in maintenance system, right? It seems the seven Sirtuins are that. Take SIRT6, for example. Evidence points to it being essential to / directly enabling DNA repair[3], and telomere maintenance[4], while reducing gluconeogensis[5] and inflammation. SIRT2 supports insulin sensitivity through multiple pathways[6], and helps regulate proper cell division, i.e. in the ordinary case, helps prevent the formation of tumors[7]. IMPORTANT NOTE This may only be beneficial if you don't already have cancer - in the other case more SIRT2 could help to stabilize your cancer cells in their division and increase proliferation.[8] So please, talk to your doctor. One more, because I'm enjoying this: for SIRT3, researchers studied a population and found that genes enhancing its production where "virtually absent" in men older than 90.[9] Mice bred to lack SIRT3 developed breast cancer, and the researchers proposed "that SIRT3 is ideally situated to function as a mitochondrial fidelity protein, and by extension, loss of function could result in a damage permissive and tumorigenic cellular environment" [10] That's three of seven. Other multi-SIRT effects include: * possibly preventing stroke and improving recovery in its aftermath [11] * being essential to retinal function / vision [12] So Sirtuins are important, and they're powered by NAD+, but NAD+ availability declines as we age, reducing their ability to play that role, and contributing to consequent decline and dysfunction with age. Supplementing NMN helps offset that decline, to keep those systems working as they should. So I'm calling it here. My best minimal health / longevity stack is: NMN, Kado-3, and Magnesium. If you want to add another for good measure, look at bioflavonoids Quercetin or Apigenin, both inhibitors of CD38, one probable cause of age-related NAD+ decline.[13] Thanks for reading. Live long and prosper. Disclaimer: I'm an engineer, not a scientist or a doctor, so my preference is to support actions which I expect to work, rather than ones which I know with certainty will work. Ergo, this is not medical advice, this is my judgment based on my limited and potentially misguided analysis of the human body as a system. Footnotes: [1] As with Resveratrol, which activates SIRT1 [2] As with Nicotinamide Riboside, which is the precursor to NMN and externally mediated by NAMPT, etc. NMN needs no co-factor. [3] "SIRT6 is [...] is required for normal base excision repair of DNA damage in mammalian cells. Deficiency of SIRT6 in mice leads to abnormalities that overlap with aging-associated degenerative processes." https://en.wikipedia.org/wiki/Sirtuin_6 https://en.wikipedia.org/wiki/Sirtuin_6 [4] "We propose that SIRT6 contributes to the propagation of a specialized chromatin state at mammalian telomeres, which in turn is required for proper telomere metabolism and function. Our findings constitute the first identification of a physiological enzymatic activity of SIRT6, and link chromatin regulation by SIRT6 to telomere maintenance and a human premature ageing syndrome." https://www.ncbi.nlm.nih.gov/pubmed/18337721 https://www.ncbi.nlm.nih.gov/pubmed/18337721 [5] As with Metformin, which has evidence for longevity effects. [6] "SIRT2 inhibits adipogenesis by deacetylating FOXO1 and thus may protect against insulin resistance. SIRT2 sensitizes cells to the action of insulin by physically interacting with and activating Akt and downstream targets." https://en.wikipedia.org/wiki/Sirtuin_2 https://en.wikipedia.org/wiki/Sirtuin_2 [7] "SirT2-deficient animals exhibit genomic instability and chromosomal aberrations and are prone to tumorigenesis" http://genesdev.cshlp.org/content/early/2013/03/04/gad.211342.112 http://genesdev.cshlp.org/content/early/2013/03/04/gad.21134... [8] "Our data suggest that SIRT2 is the sirtuin predominantly involved in breast tumourigenesis and prognosis. It indicates that SIRT2 acts as a tumour suppressor or tumour promoter dependent upon breast tumour grade." https://www.ncbi.nlm.nih.gov/pubmed/24183459 https://www.ncbi.nlm.nih.gov/pubmed/24183459 [9] https://www.sciencedirect.com/science/article/pii/S0888754304003088?via%3Dihub https://www.sciencedirect.com/science/article/pii/S088875430... [10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711519/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711519/ [11] "NMN and NAD treatment also enhanced proliferation and differentiation of cultured neural stem cells in vitro. Knockdown of sirtuin deacetylases (SIRT1, SIRT2, or SIRT6) significantly reduced the proneuro-genesis effect[...]. Thus, we provide the first evidence that Nampt–NAD cascade is not only crucial against acute brain ischemic injury but also important for postischemic regeneration." http://stroke.ahajournals.org/content/strokeaha/46/7/1966.full.pdf http://stroke.ahajournals.org/content/strokeaha/46/7/1966.fu... [12] "We further demonstrate that the NAD+-dependent mitochondrial deacylases SIRT3/SIRT5 play important roles in retinal homeostasis and that NAD+ deficiency causes SIRT3 dysfunction. These findings demonstrate that NAD+ biosynthesis is essential for vision" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104206/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104206/ [13] "These findings suggest that the efficacy of NAD+ precursors may be enhanced by co-supplementation with CD38 inhibitors" https://www.sciencedirect.com/science/article/pii/S1550413116302443 https://www.sciencedirect.com/science/article/pii/S155041311... http://www.timelesslifemag.com/index.php/2016/06/29/quercetin-apegenin-may-slow-down-the-escalating-nad-consumption-by-cd38-as-we-age/ http://www.timelesslifemag.com/index.php/2016/06/29/querceti...
FlyingSideKick 9y ago
I’ve been considering taking these supplements but I’m concerned about increased risk of cancer. Have there been updates on this since the publication of this study? https://siteman.wustl.edu/pathway-linked-slower-aging-also-fuels-brain-cancer/ https://siteman.wustl.edu/pathway-linked-slower-aging-also-f...
- partiallypro 9y ago
  Just skimmed the article, and it seems to me that they are more looking into this to find a treatment for brain cancer than making a direct causality from the supplement itself. Basically when someone does have brain cancer, they could limit NAMPT to help in treatment. That's how I read it at least, maybe I'm misinterpreting. There is these quote: “We didn’t directly demonstrate that taking NAD+ precursors makes tumors grow faster, but one implication of our work is that if you want to take anti-aging NAD+ precursors, you might want to keep in mind that we don’t yet understand all the risks.” "Furthermore, the scientists found that glioblastoma cells responded to radiation therapy – a standard therapy used to treat the disease in people – by increasing expression of NAD+ pathway genes, and that inhibiting NAMPT before dosing the cells with radiation made them easier to kill."
clumsysmurf 9y ago
I'm confused, as already mentioned at the bottom of the article, there are other supplements to boost NAD+ like nicotinamide riboside. Is this research pointing to NMN having a greater impact on NAD+ than nicotinamide riboside ?
mjhoyer 9y ago
FOXO4-DRI seems much more promising with less side effects (none known) than NAD+
JulianMorrison 9y ago
1. Headline ends in "?". The answer is "no". 2. Longevity breakthrough discovered in mice. Mice biology doesn't bother picking the low hanging fruit of longevity. Said breakthrough picks some of that low hanging fruit. Chances are near-certainty it won't work in humans.
- yodsanklai 9y ago
  > Chances are near-certainty it won't work in humans Still an interesting result, even though it can't be applied directly to humans. I'm not familiar with the field, but it sounds like an extraordinary feat to be able to rejuvenate an animal.
  - Retric 9y ago
    It might sound that way, but it's really not difficult to rejuvenate mice. The metabolic burden associated with living longer is not worth it for wild mice.
kup0 9y ago
The risk of causing autoimmune diseases due to increased sirtuins seems like it should give companies like Elysium Health some pause on this. It is possible the risks are low, but that is an incredibly severe, permanent side-effect. That said, they know far more about the compounds/molecules involved than I do.
pandasun 9y ago
As someone with depression, I would have no interest in this.

160 points by gscott 9y ago

"In the latest advance, biologists reported on Thursday that a molecule already sold by supplement makers (even as scientists scramble to understand it) restored youthfulness to blood vessels in 20-month-old mice, an age comparable to 70 years in people..." So which supplement is it? If it's already sold by supplement makers, have there been any reports of similar effects in people?

mrfusion 9y ago
The amazon reviews are pretty positive fwiw .. probably not much.
ridgeguy 9y ago
From the article: "The new study, in Cell, found that boosting mice’s levels of the naturally occurring molecule NMN, which humans also have, increased levels of another called NAD+." NMN is nicotinamide mononucleotide, available on Amazon.
deleted 9y ago
[deleted]
kurthr 9y ago
It's NMN (NICOTINAMIDE MONONUCLEOTIDE) and sold through everyone including Wal-Mart and Amazon. Whether it works... on humans? I don't know and I'm not aware of any (completed) human studies.
bitL 9y ago
There was a thread a year or so ago on HN where some people mentioned that they narrowed down their supplements to NMN and something else and were happy about that.
- zspade 9y ago
  I believe it was NMN and Resveratrol (or Pterostilbene.).

mhuffman 9y ago

A link[1] to the actual research says "Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels." [1] http://www.cell.com/cell/fulltext/S0092-8674(18)30152-1 http://www.cell.com/cell/fulltext/S0092-8674(18)30152-1

1024core 9y ago

The compound in question is nicotinamide mononucleotide (NMN). Back in 2016, Keio university in Japan started a human study on its effects on aging: https://www.keio.ac.jp/en/press-releases/2016/Dec/27/49-19313/ https://www.keio.ac.jp/en/press-releases/2016/Dec/27/49-1931... I haven't heard anything since about what happened to the study.

trakam 9y ago
Sounds like a good origin story for Kaiju
AstralStorm 9y ago
Exactly nothing. NMN failed exploratory trials multiple times. (Similar to resveratrol.) It is just that the regulations ate not being published due to not being interesting to investors and sponsors. NMN might be useful for people with niacin metabolism issues perhaps.

reasonattlm 9y ago

If you are old enough to remember the hype about resveratrol and sirtuins, that eventually resolved to nothing at all of any great use for human medicine, this is basically the same people singing the same song about roughly the same area of biochemistry. On the face of past events, they can't really be trusted to tell you how great it is and how promising it is, so just read the facts and compare with other studies. About the most one can say about this is that manipulation of NAD+ levels is a better exercise mimetic than manipulation of sirtuins proved to be. What it helps to do is explain some of the underpinnings of studies that show a great deal of muscle loss is secondary aging - i.e. disuse. It also suggests that loss of capillaries is a more important mechanism in sarcopenia than other groups believe to be the case, though I think it very possible that this is secondary to stem cell activity loss. The evidence for stem cell decline to be the primary cause of sarcopenia is very good. [1] There is a faction that thinks capillary loss is important in all tissues. [2] Go look at the studies showing resistance training to be pretty effective in seniors before getting excited about NAD+ boosters. The resistance training is probably cheaper and better. One still has studies such as the one showing that dietary nicotinamide doesn't do a great deal in mice [3] - like sirtuin manipulations, it helps fat mice a little, but is distinctly unimpressive otherwise. Remember that calorie restriction extends life by 40% in mice, but probably five years or less in humans - the effects of all these stress response related mechanisms of metabolic manipulation work through a few overlapping core processes, and scale down with species longevity. That's why I see them as a dead end in comparison to other strategies. [1]: https://www.urmc.rochester.edu/news/story/4788/stem-cells-may-be-the-key-to-staying-strong-in-old-age.aspx https://www.urmc.rochester.edu/news/story/4788/stem-cells-ma... [2]: https://doi.org/10.1159/000477402 https://doi.org/10.1159/000477402 [3]: https://doi.org/10.1016/j.cmet.2018.02.001 https://doi.org/10.1016/j.cmet.2018.02.001

xcavier 9y ago
There are quite a few supplements that operate to boost NAD+ levels. The one I take personally is https://www.iherb.com/pr/Thorne-Research-Niacel-250-Nicotinamide-Riboside-60-Veggie-Capsules/69577 https://www.iherb.com/pr/Thorne-Research-Niacel-250-Nicotina... For general background on the science + nutrition approaches, see https://www.selfhacked.com/blog/nad-important-increase/ https://www.selfhacked.com/blog/nad-important-increase/

KaoruAoiShiho 9y ago

I'm not a biologist so here's a dumb question. There's a lot of talk about replicating the study experimentally but do we simply not understand biology well enough to make a theoretical analysis? Basically can we not understand on a fundamental level why it works in mice and why it might or might not work for humans?

taneq 9y ago
> do we simply not understand biology well enough to make a theoretical analysis? Correct. We understand bits and pieces of biology but we don't understand the entire system well enough to predict anything with any confidence.
toolbox 9y ago
The short answer here is yes. We're constantly working to get more complete models, but surprisingly big effects can come from surprisingly small pieces of the puzzle. We still don't even really understand how Tylenol/Paracetamol/Acetaminophen works! A great example of the gap between our current models and what would be sufficient comes from the COX-2 inhibitors (Vioxx/Celebrex). Ibuprofin (Motrin/Advil) and other NSAIDs modulate both COX-1 and COX-2 receptors in the body to reduce inflammation, but inhibiting COX-1 also causes stomach damage. The early COX-2-specific inhibitors were designed from the ground up using our best models, which were thought to be well-understood. Unfortunately, after several years on the market, it was discovered that this also came with a large increased risk of heart attacks and strokes. The body just has so so many moving pieces, and while we're getting better, it's going to be some time before we are able to base these studies entirely on theory, and when we get there we'll be able to skip the mice entirely!
- ethbro 9y ago
  As my dad (pathologist) put it, "Nature is a lazy bitch. She'd rather repurpose the same thing 50 times than develop something novel." So add up random biochemical pathway * X million years of evoltion, and one begins to understand the fun of drug discovery and testing. "We know this is the pathway involved in heart disease. We know this chemical compound is effective against that pathway. ... Now why are all our mouse models getting erections?"

wakkaflokka 9y ago

So if one were to try taking NMN as a supplement but had no idea which brands were legitimate, what should they do? Go off Amazon reviews? Recommendations anybody?

shurth 9y ago
I use Amazon reviews but I try to stay conscious that sexy labels/marketing influences people. When in doubt, stick with the high quality, no additives, stuff like Thorne.
- CodeWriter23 9y ago
  Yeah also pay attention to the review dates. I wanted to buy a lightning / audio split cable for my iPhone. I noticed the vendor had 800+ 5 star reviews and none for 1-4 stars. Then I noticed all the reviews had been entered in the previous 3 days. /fakereviews
- amelius 9y ago
  I read a lot of complaints about counterfeits on Amazon (not this particular product), so I'm avoiding them especially when it comes to food and supplements.

stevenwoo 9y ago

I heard about this on NPR last week - even if it could make old people's blood vessels youthful, it seems like it would be better to just make the person change their diet and their exercise regimen, assuming exercise was possible. This chemical only affected blood vessel health. This is only one component of health. Bone density requires load bearing exercise. Another recent study pointed out lack of exercise led to nerves to major muscle groups fading away with lack of use - led to muscle loss - one has to use those muscles to use the nerves, age related muscle loss can be staved off by exercise of the muscle groups in question.

themodelplumber 9y ago
The supplement or the pill has magical abilities though. Many people who will say "I die when I die" when told to diet or exercise will take a pill with no complaints. And as a hobby dieter & big loser: Once you realize diet is something requiring long-term conscientiousness, the truth and enormity of the change can hit very hard. It is an emotional roller coaster that can just as easily make people more fat than when they started.
- NIL8 9y ago
  "And as a hobby dieter & big loser" - I love this.
- jack_pp 9y ago
  If they don't care about their own health and longevity I would argue their lives shouldn't be extended against their own will. Should we also give free houses and luxury cars to people who refuse to work?
  - thriftwy 9y ago
    Shoud we sell stuff to people who refuse to work out? The answer is obvious yet you're not seeing it.
  - distances 9y ago
    > Should we also give free houses and luxury cars to people who refuse to work? I know you meant this as a rhetorical question, but yes, I think society should provide free basic housing for those that can't afford it, whatever the reason.

kuwze 9y ago

I think the future of age-related research is going to focus on inflammation. There is already a term for it: Inflamm-aging[0]. [0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963991/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963991/

reasonattlm 9y ago
A good recent paper on sources of inflammation in aging: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850851/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850851/ As it points out, the most obvious and promising of current prospects for reducing inflammation is the selective destruction of senescent cells. Though I think that the clearance and recreation of the entire immune system, to remove all of the senescent, exhausted, misconfigured, etc, immune cells is also a promising path, albeit further away from being safe enough to apply to old people.

Empact 9y ago

This article prompted me to research and write a plea for my friends to take this supplement (I've been on it for a few months, before that took Nicotinamide Riboside, NMN's precursor): Please consider taking NMN for health and longevity. Nicotinamide Mononucleotide (NMN) is a direct precursor of NAD+ which broadly activates/energizes the Sirtuin pathways. Previous interventions either activated only one of these pathways[1] or activated them less effectively[2]. Why all the fuss about Sirtuin pathways? Well, it makes sense that your body would have a built-in maintenance system, right? It seems the seven Sirtuins are that. Take SIRT6, for example. Evidence points to it being essential to / directly enabling DNA repair[3], and telomere maintenance[4], while reducing gluconeogensis[5] and inflammation. SIRT2 supports insulin sensitivity through multiple pathways[6], and helps regulate proper cell division, i.e. in the ordinary case, helps prevent the formation of tumors[7]. IMPORTANT NOTE This may only be beneficial if you don't already have cancer - in the other case more SIRT2 could help to stabilize your cancer cells in their division and increase proliferation.[8] So please, talk to your doctor. One more, because I'm enjoying this: for SIRT3, researchers studied a population and found that genes enhancing its production where "virtually absent" in men older than 90.[9] Mice bred to lack SIRT3 developed breast cancer, and the researchers proposed "that SIRT3 is ideally situated to function as a mitochondrial fidelity protein, and by extension, loss of function could result in a damage permissive and tumorigenic cellular environment" [10] That's three of seven. Other multi-SIRT effects include: * possibly preventing stroke and improving recovery in its aftermath [11] * being essential to retinal function / vision [12] So Sirtuins are important, and they're powered by NAD+, but NAD+ availability declines as we age, reducing their ability to play that role, and contributing to consequent decline and dysfunction with age. Supplementing NMN helps offset that decline, to keep those systems working as they should. So I'm calling it here. My best minimal health / longevity stack is: NMN, Kado-3, and Magnesium. If you want to add another for good measure, look at bioflavonoids Quercetin or Apigenin, both inhibitors of CD38, one probable cause of age-related NAD+ decline.[13] Thanks for reading. Live long and prosper. Disclaimer: I'm an engineer, not a scientist or a doctor, so my preference is to support actions which I expect to work, rather than ones which I know with certainty will work. Ergo, this is not medical advice, this is my judgment based on my limited and potentially misguided analysis of the human body as a system. Footnotes: [1] As with Resveratrol, which activates SIRT1 [2] As with Nicotinamide Riboside, which is the precursor to NMN and externally mediated by NAMPT, etc. NMN needs no co-factor. [3] "SIRT6 is [...] is required for normal base excision repair of DNA damage in mammalian cells. Deficiency of SIRT6 in mice leads to abnormalities that overlap with aging-associated degenerative processes." https://en.wikipedia.org/wiki/Sirtuin_6 https://en.wikipedia.org/wiki/Sirtuin_6 [4] "We propose that SIRT6 contributes to the propagation of a specialized chromatin state at mammalian telomeres, which in turn is required for proper telomere metabolism and function. Our findings constitute the first identification of a physiological enzymatic activity of SIRT6, and link chromatin regulation by SIRT6 to telomere maintenance and a human premature ageing syndrome." https://www.ncbi.nlm.nih.gov/pubmed/18337721 https://www.ncbi.nlm.nih.gov/pubmed/18337721 [5] As with Metformin, which has evidence for longevity effects. [6] "SIRT2 inhibits adipogenesis by deacetylating FOXO1 and thus may protect against insulin resistance. SIRT2 sensitizes cells to the action of insulin by physically interacting with and activating Akt and downstream targets." https://en.wikipedia.org/wiki/Sirtuin_2 https://en.wikipedia.org/wiki/Sirtuin_2 [7] "SirT2-deficient animals exhibit genomic instability and chromosomal aberrations and are prone to tumorigenesis" http://genesdev.cshlp.org/content/early/2013/03/04/gad.211342.112 http://genesdev.cshlp.org/content/early/2013/03/04/gad.21134... [8] "Our data suggest that SIRT2 is the sirtuin predominantly involved in breast tumourigenesis and prognosis. It indicates that SIRT2 acts as a tumour suppressor or tumour promoter dependent upon breast tumour grade." https://www.ncbi.nlm.nih.gov/pubmed/24183459 https://www.ncbi.nlm.nih.gov/pubmed/24183459 [9] https://www.sciencedirect.com/science/article/pii/S0888754304003088?via%3Dihub https://www.sciencedirect.com/science/article/pii/S088875430... [10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711519/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711519/ [11] "NMN and NAD treatment also enhanced proliferation and differentiation of cultured neural stem cells in vitro. Knockdown of sirtuin deacetylases (SIRT1, SIRT2, or SIRT6) significantly reduced the proneuro-genesis effect[...]. Thus, we provide the first evidence that Nampt–NAD cascade is not only crucial against acute brain ischemic injury but also important for postischemic regeneration." http://stroke.ahajournals.org/content/strokeaha/46/7/1966.full.pdf http://stroke.ahajournals.org/content/strokeaha/46/7/1966.fu... [12] "We further demonstrate that the NAD+-dependent mitochondrial deacylases SIRT3/SIRT5 play important roles in retinal homeostasis and that NAD+ deficiency causes SIRT3 dysfunction. These findings demonstrate that NAD+ biosynthesis is essential for vision" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104206/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104206/ [13] "These findings suggest that the efficacy of NAD+ precursors may be enhanced by co-supplementation with CD38 inhibitors" https://www.sciencedirect.com/science/article/pii/S1550413116302443 https://www.sciencedirect.com/science/article/pii/S155041311... http://www.timelesslifemag.com/index.php/2016/06/29/quercetin-apegenin-may-slow-down-the-escalating-nad-consumption-by-cd38-as-we-age/ http://www.timelesslifemag.com/index.php/2016/06/29/querceti...

FlyingSideKick 9y ago

I’ve been considering taking these supplements but I’m concerned about increased risk of cancer. Have there been updates on this since the publication of this study? https://siteman.wustl.edu/pathway-linked-slower-aging-also-fuels-brain-cancer/ https://siteman.wustl.edu/pathway-linked-slower-aging-also-f...

partiallypro 9y ago
Just skimmed the article, and it seems to me that they are more looking into this to find a treatment for brain cancer than making a direct causality from the supplement itself. Basically when someone does have brain cancer, they could limit NAMPT to help in treatment. That's how I read it at least, maybe I'm misinterpreting. There is these quote: “We didn’t directly demonstrate that taking NAD+ precursors makes tumors grow faster, but one implication of our work is that if you want to take anti-aging NAD+ precursors, you might want to keep in mind that we don’t yet understand all the risks.” "Furthermore, the scientists found that glioblastoma cells responded to radiation therapy – a standard therapy used to treat the disease in people – by increasing expression of NAD+ pathway genes, and that inhibiting NAMPT before dosing the cells with radiation made them easier to kill."

clumsysmurf 9y ago

I'm confused, as already mentioned at the bottom of the article, there are other supplements to boost NAD+ like nicotinamide riboside. Is this research pointing to NMN having a greater impact on NAD+ than nicotinamide riboside ?

mjhoyer 9y ago

FOXO4-DRI seems much more promising with less side effects (none known) than NAD+

JulianMorrison 9y ago

1. Headline ends in "?". The answer is "no". 2. Longevity breakthrough discovered in mice. Mice biology doesn't bother picking the low hanging fruit of longevity. Said breakthrough picks some of that low hanging fruit. Chances are near-certainty it won't work in humans.

yodsanklai 9y ago
> Chances are near-certainty it won't work in humans Still an interesting result, even though it can't be applied directly to humans. I'm not familiar with the field, but it sounds like an extraordinary feat to be able to rejuvenate an animal.
- Retric 9y ago
  It might sound that way, but it's really not difficult to rejuvenate mice. The metabolic burden associated with living longer is not worth it for wild mice.

kup0 9y ago

The risk of causing autoimmune diseases due to increased sirtuins seems like it should give companies like Elysium Health some pause on this. It is possible the risks are low, but that is an incredibly severe, permanent side-effect. That said, they know far more about the compounds/molecules involved than I do.

pandasun 9y ago

As someone with depression, I would have no interest in this.