Rejuvenating blood vessels and vitality for an antiaging effect

David Sinclair and his team at Harvard Medical School claim to be able to reverse the aging of blood vessels and it restores youthful vitality.

Using the synthetic precursors of two molecules naturally present in the body, the scientists also managed to reverse blood vessel demise and muscle atrophy in aging mice, boosting their exercise endurance in the process.

They used a chemical compound called NMN, a NAD+ precursor.

The team gave NMN over two months to a group of mice that were 20 months old—the rough equivalent of 70 in human years. NMN treatment restored the number of blood capillaries and capillary density to those seen in younger mice. Blood flow to the muscles also increased and was significantly higher than blood supply to the muscles seen in same-age mice that didn’t receive NMN.

The most striking effect, however, emerged in the aging mice’s ability to exercise. These animals showed between 56 and 80 percent greater exercise capacity, compared with untreated mice the study showed. The NMN-treated animals managed to run 430 meters, or about 1,400 feet, on average, compared with 240 meters, or 780 feet, on average, for their untreated peers.

To see whether the effects of NMN could be further augmented, the researchers added a second compound to the treatment regimen. The compound, sodium hydrosulfide (NaHS), is a precursor to hydrogen sulfide, which also boosts the activity of SIRT1.

A group of 32-month-old mice—the rough equivalent to 90 in human years—receiving the combo treatment for four weeks were able to run, on average, twice as long as untreated mice. In comparison, mice treated with NMN alone ran 1.6 times farther, on average, than untreated animals.

Cell – Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging

Highlights

• Reduced blood flow with age is due to loss of endothelial NAD+-SIRT1 activity
• NAD+ and H2S control muscle angiogenesis and increase endurance in old mice
• The NAD precursor NMN mimics and augments exercise by inhibiting NICD-Notch
• Neovascularization is as important as mitochondria for rejuvenating muscle

Cell Metabolism – Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence

Nicotinamide adenine dinucleotide (NAD), the cell’s hydrogen carrier for redox enzymes, is well known for its role in redox reactions. More recently, it has emerged as a signaling molecule. By modulating NAD +-sensing enzymes, NAD + controls hundreds of key processes from energy metabolism to cell survival, rising and falling depending on food intake, exercise, and the time of day. NAD + levels steadily decline with age, resulting in altered metabolism and increased disease susceptibility. Restoration of NAD + levels in old or diseased animals can promote health and extend lifespan, prompting a search for safe and efficacious NAD-boosting molecules that hold the promise of increasing the body’s resilience, not just to one disease, but to many, thereby extending healthy human lifespan.

162 thoughts on “Rejuvenating blood vessels and vitality for an antiaging effect”

  1. Is this going to work in humans in the same way as in mice? That is always really hard to tell. Do mice, which live 2-3 years in captivity, experience the same intrinsic damage to their mitochondrial DNA as humans do over 70-80 years? Is the extrinsic damage which affects mitochondrial function over time the same in mice and humans? w­ww.fightaging.o­rg/archives/2006/10/how-age-damaged-mitochondria-cause-your-cells-to-damage-you/ Lifespan.io/Leafscience are going to carry out a fundraiser for another David Sinclair lab study on boosting NAD+ levels in mice. More data and repeating experiments is always good. But I wonder if the results and model will actually tell us much about humans. I also wonder how much it would cost to set up a tiny phase 1 human trial? [As an aside, is it just me who finds that Leafscience.o­rg having a different name Lifespan.i­o for their crowdfunding a confusion? I think the name Lifespan.i­o is better as it is more descriptive of what they do, so they should just switch to using that everywhere and drop the legacy leafscience name.]

  2. Good article from Steve Hill of Leafscience on NAD+, and why it declines with age: w­ww.leafscience.o­rg/nad-and-aging/ “We now know that CD38 is the major culprit in NAD+ decline, but why does it fall in the first place? CD38 expression and activity are known to be induced by inflammatory cytokines and bacterial endotoxins, such as lipopolysaccharides (LPS) [8-11]. This strongly suggests that the smouldering, age-related, chronic inflammation commonly called “inflammaging” may be driving the increased expression of CD38 and the resulting NAD+ decline. This is because senescent cells secrete CD38 as part of the pro-inflammatory cytokine cocktail known as the senescence-associated secretory phenotype (SASP). This mixture of pro-inflammatory signals includes CD38, and senescent cells accumulate during aging as the immune system increasingly fails to remove the problem cells. Thus, more senescent cells almost certainly means more CD38 and less NAD+ available. The same goes for increasing amounts of cell debris and microbial burden; these also drive inflammaging, thus increasing CD38, decreasing NAD+, and causing age-related dysfunction.”

  3. Can someone tell me how this varies from Nicotinamide Riboside? Also: is this going to work the same way in humans as in mice? Can we take it now? If not now, when? Did the mice .. live any longer?

  4. So, I’m only thirty-five, but I began working a desk job a few years ago, which has, sadly, led to a decrease in health. I’m finally turning that around, but when I began taking an NAD+ precursor, I did notice an increase in my ability to exercise, and a decrease in muscle ache and joint pain. In fact, the joint pains I had felt in my knees for almost fifteen years pretty much vanished. My vision did improve (albeit only slightly, so I can’t peg the precursor for that), and my body can sustain longer periods of physical activity, near or even above levels which I could sustain when I was working at Starbucks for approximately seven years and was constantly in my feet. That’s something quite significant, to me. Also, I can dance longer at anime convention raves (take that as you will >_> ) drinking only water and no coffee, which is a major improvement. What I mean by that, is that I don’t require as much caffeine, i.e. stimulant, to sustain healthy energy levels. I’m not saying go out and buy an NAD+ precursor, since I’m not at the age at which I should really need one, myself, and everyone’s body is different. But I did notice improvements. Personal anecdote, but there it is.

  5. Can someone tell me how this varies from Nicotinamide Riboside?Also: is this going to work the same way in humans as in mice? Can we take it now? If not now when? Did the mice .. live any longer?

  6. So I’m only thirty-five but I began working a desk job a few years ago which has sadly led to a decrease in health. I’m finally turning that around but when I began taking an NAD+ precursor I did notice an increase in my ability to exercise and a decrease in muscle ache and joint pain. In fact the joint pains I had felt in my knees for almost fifteen years pretty much vanished. My vision did improve (albeit only slightly so I can’t peg the precursor for that) and my body can sustain longer periods of physical activity near or even above levels which I could sustain when I was working at Starbucks for approximately seven years and was constantly in my feet. That’s something quite significant to me. Also I can dance longer at anime convention raves (take that as you will >_> ) drinking only water and no coffee which is a major improvement. What I mean by that is that I don’t require as much caffeine i.e. stimulant to sustain healthy energy levels. I’m not saying go out and buy an NAD+ precursor since I’m not at the age at which I should really need one myself and everyone’s body is different. But I did notice improvements. Personal anecdote but there it is.

  7. Senescent cell clearance and generic modification of our mitochondria, so that they produce NAD+, seems to be our best way forward. Unity biotechnology is in phase 1 trials till November and oisin biotechnology starts phase 1 trials in 2019.

  8. If it’s micrograms, you could get lab grade. It’s still dirt cheap. The problem is that it produces H2S on exposure to water. Not rapidly, though. The details of administering it would be interesting. Unfortunately, they’re behind CELL’s paywall.

  9. This suggests that senolytics should have similar benefits as these chemical precursors, as a side-effect of reducing senescent cells, in addition to other benefits.

  10. NaHS converts to H2S, which is toxic (it’s also what contributes to the smell). So I’d imagine you’ll need a very small dose, probably in the micrograms. Certainly not in industrial quantities. I’m guessing the highly available form is technical grade for various industrial uses. That would also have a bunch of impurities which are ok for the industrial use, but not for consumption. What you want is a food supplement in pill form.

  11. NMN is a “precursor” for Nicotinamide Riboside, which is to say, it’s what it is made out of. Generally in biology, if you supply more of a precursor, you get more of the end product. Sometimes it’s the better way to approach increasing something, because the desired end product isn’t very bioavailable, or degrades rapidly, or something like that. Anyway, it’s easily available as a supplement, I might give it a try. I don’t think I’ll be trying the sodium hydrosulfide, though. Easily available, but according to the MSDS sheet, it’s corrosive, stinks, and even in low concentrations deadens your sense of smell. Unless the necessary dose is extremely low, I can’t see people using it.

  12. Both these are readily available, but sodium hydrosulfide *stinks*. Rotten egg smell. Maybe you can force a mouse to eat it anyway or starve, but as with any aversive treatment, you risk conflating the effect of the compound with calorie deprivation.

  13. Senescent cell clearance and generic modification of our mitochondria so that they produce NAD+ seems to be our best way forward. Unity biotechnology is in phase 1 trials till November and oisin biotechnology starts phase 1 trials in 2019.

  14. If it’s micrograms you could get lab grade. It’s still dirt cheap. The problem is that it produces H2S on exposure to water. Not rapidly though. The details of administering it would be interesting. Unfortunately they’re behind CELL’s paywall.

  15. This suggests that senolytics should have similar benefits as these chemical precursors as a side-effect of reducing senescent cells in addition to other benefits.

  16. NaHS converts to H2S which is toxic (it’s also what contributes to the smell). So I’d imagine you’ll need a very small dose probably in the micrograms. Certainly not in industrial quantities.I’m guessing the highly available form is technical grade for various industrial uses. That would also have a bunch of impurities which are ok for the industrial use but not for consumption. What you want is a food supplement in pill form.

  17. NMN is a precursor”” for Nicotinamide Riboside”” which is to say it’s what it is made out of. Generally in biology if you supply more of a precursor you get more of the end product. Sometimes it’s the better way to approach increasing something because the desired end product isn’t very bioavailable or degrades rapidly or something like that.Anyway it’s easily available as a supplement I might give it a try. I don’t think I’ll be trying the sodium hydrosulfide though. Easily available but according to the MSDS sheet it’s corrosive stinks and even in low concentrations deadens your sense of smell.Unless the necessary dose is extremely low”” I can’t see people using it.”””

  18. Both these are readily available but sodium hydrosulfide *stinks*. Rotten egg smell.Maybe you can force a mouse to eat it anyway or starve but as with any aversive treatment you risk conflating the effect of the compound with calorie deprivation.

  19. Yes, H2S and NaOH, which is also a problem. I doubt it’s administered directly. It probably needs to be wrapped in something that would control its release, and combined with a buffer or mild acid to neutralize the NaOH afterwards. Probably not a kitchen chemistry project, even if the raw materials are available. Anyway, there’s no such thing as “lab grade”. Depending on chemical, lab suppliers may provide anything from ultra-pure references, through high-purity biology grade, through pharma grade with special manufacturing controls, through food grade (if it’s used in food), through reagent grade (typically 90-99% purity), to cheap technical grade. Depending on regulations, you may need a special license to buy some of these stuff. Generally, the higher the purity, the more regulation, and the lower the sales volume, the more expensive it is. You can go to sigmaaldrich (dot) com, and do a search. They’re one of the major lab chemical suppliers. From what I can see, they currently have one grade of NaSH. Not too expensive, but doesn’t list the purity. It’s probably reagent grade, in which case it may still contain toxic impurities.

  20. Inflammation may also be caused by AGEs (Advanced glycation end-products). The formation of AGEs can be reduced by Metformin, Pyridoxal-5-phosphate (P-5-P), L Carnosine, and Benfotiamine. And reduced dietary intake of AGEs may also reduce levels, but apparently there is still debate on that. That can be done by using avocado oil, corn oil, safflower oil, and sunflower oil. Pistachio oil is probably good too. Most of the nuts have a lot of AGEs…but pistachios seem to be ok. You want cold pressed oils and definitely not roasted oils. And avoid olive oil, peanut oil, sesame oil and canola oil. And cooking everything that you cook at low temperatures: no grilling, frying, or roasting. Avoid butter, any kind of fried potato and bacon especially. Avoid things that are beaten: butter, mayonnaise, various sauces. High temperature and beating generates these things. Acid can dramatically reduce the formation, so marinating before cooking is good. But you can’t just put something acidic on the food after you cooked it. It must be between the cooking surface and the food. Boiled, stewed or microwaved is best. Search: “Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet

  21. Both NMN and NR are supposed to lead to the same endpoint of NAD+. Like Brett said, there are sometimes reasons to use a precursor further up the chain, and I’ve seen some people make such arguments for NMN, but I don’t think it’s really clear. NR has more human studies, and they are promising. NMN is said to have stronger results than NR… in some rodent studies. It’s newer and has fewer human studies. Both are for sale. Honestly, if either of them will improve your health, the other one probably will too. Just maybe not as much per mg.

  22. Both NMN and NR are supposed to lead to the same endpoint of NAD+. Like Brett said there are sometimes reasons to use a precursor further up the chain and I’ve seen some people make such arguments for NMN but I don’t think it’s really clear. NR has more human studies and they are promising. NMN is said to have stronger results than NR… in some rodent studies. It’s newer and has fewer human studies. Both are for sale. Honestly if either of them will improve your health the other one probably will too. Just maybe not as much per mg.

  23. If you look at the original paper, they word it as the H2S helps boost the main NMN affect, just as exercise does. So do some exercise and you won’t need the H2S. Though I didn’t see that explicitly in the actual results section. Also, the “exercise” was to have the mice run for 20 minutes until exhausted. Where “exhausted” means that a 10 second electric shock wouldn’t get the mice running again. So you need a sadist with a taser to get you doing that daily.

  24. The purpose of this research was not to find a human, or even a mouse, treatment. It was rather to investigate the biochemistry in the process. Which means they may well have glossed over issues that are unimportant for their work, but vital for treatment development. For example (and I’m not saying this applies, but it’s just an illustration) if the mice were operating in a diet/genetic/activity level space where they were actually deficient in say vitamin B3, then supplementing would make them more healthy. But doesn’t mean that giving more B3 to a human who is not deficient will help that human.

  25. I posted a nice long reply which has been eaten. Probably contained too many facts which set off the vuucke defense system. ANYWAY, just go to sci-hub and you can get the paper for free. And the full paper contains useful things like the actual Sigma Aldrich catalog numbers for the various chemicals.

  26. Go to sci-hub and you can get free access to the paper (most papers actually). There is a lot of detail. Such as the H2S being bought from Sigma-Aldrich Cat#161527.

  27. From the abstract at the link “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),” So you get the same effect as H2S by doing exercise. And 80% of the benefit comes from the NMN anyway. The H2S or exercise just boosts the effect a bit. Though the type of exercise isn’t fun, they had the little fellows running to exhaustion over 10 to 40 minutes. And the “To restore NAD+ levels, we administered NMN to 18-month-old mice via drinking water for 2 months at 400 mg/kg/day” which is what I would call a very high dose. It doesn’t scale exactly with mass, but 400 mg/kg/day is about 40 grams/day for me. You guys know you can get the papers for free from sci-hub?

  28. Much of the time, life extension treatments that work on mice are only bringing things closer to human standards; As soon as you look, you usually find it’s something humans already implement. But, of course, it doesn’t have to be, and sometimes it will be something humans implement fairly well when young, and then do less well as we age.

  29. If you look at the original paper they word it as the H2S helps boost the main NMN affect just as exercise does. So do some exercise and you won’t need the H2S.Though I didn’t see that explicitly in the actual results section.Also the exercise”” was to have the mice run for 20 minutes until exhausted. Where “”””exhausted”””” means that a 10 second electric shock wouldn’t get the mice running again. So you need a sadist with a taser to get you doing that daily.”””

  30. The purpose of this research was not to find a human or even a mouse treatment. It was rather to investigate the biochemistry in the process.Which means they may well have glossed over issues that are unimportant for their work but vital for treatment development.For example (and I’m not saying this applies but it’s just an illustration) if the mice were operating in a diet/genetic/activity level space where they were actually deficient in say vitamin B3 then supplementing would make them more healthy. But doesn’t mean that giving more B3 to a human who is not deficient will help that human.

  31. I posted a nice long reply which has been eaten.Probably contained too many facts which set off the vuucke defense system.ANYWAY just go to sci-hub and you can get the paper for free.And the full paper contains useful things like the actual Sigma Aldrich catalog numbers for the various chemicals.

  32. Go to sci-hub and you can get free access to the paper (most papers actually).There is a lot of detail. Such as the H2S being bought from Sigma-Aldrich Cat#161527.

  33. From the abstract at the link 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)”””So you get the same effect as H2S by doing exercise. And 80{22800fc54956079738b58e74e4dcd846757aa319aad70fcf90c97a58f3119a12} of the benefit comes from the NMN anyway. The H2S or exercise just boosts the effect a bit.Though the type of exercise isn’t fun”””” they had the little fellows running to exhaustion over 10 to 40 minutes.And the “”””To restore NAD+ levels”””” we administered NMN to 18-month-old mice via drinking water for 2 months at 400 mg/kg/day”””” which is what I would call a very high dose. It doesn’t scale exactly with mass”””” but 400 mg/kg/day is about 40 grams/day for me.You guys know you can get the papers for free from sci-hub?”””

  34. Much of the time life extension treatments that work on mice are only bringing things closer to human standards; As soon as you look you usually find it’s something humans already implement. But of course it doesn’t have to be and sometimes it will be something humans implement fairly well when young and then do less well as we age.

  35. H2S is toxic in large amounts, but it’s actually the signaling molecule that you’re trying to introduce. It’s similar to iron and copper – useful in tiny amounts, but large amounts translate to heavy metal poisoning. They’re both easily available, but you don’t see people munching on steel bars and copper tubing. The toxic impurities I meant are various artifacts of the manufacturing process, like heavy metals, various other salts and chemicals, etc. NaSH, is made by reacting NaOH with H2S, and older processes could leave mercury traces in the NaOH. Nowadays mercury is less likely, but who knows what other contamination there might be in it. One final note: measuring microgram quantities isn’t trivial. Even milligrams require analytical scales. Not something you’d find in an average kitchen.

  36. It doesn’t count if you get her to dress in black leather beforehand. Or maybe it does. My NIH research proposal hasn’t been granted yet.

  37. I’m actually familiar with that when through chemo once. It’s why I’m pissed off at the fact that I at 240 pounds and my wife at 80 get prescribed the same dose of antibiotic if we get sick. She gets an upset stomach and I relapse because it wasn’t enough. Modern medicine is so… crude they’re not even applying what they know most of the time.It’s a good first approximation but depending on the specifics about how the liver handles different substances you can get a huge deviation from it between species.3g/day of NMN would be a bit too pricey for me. That’s like $120 a week if I buy it bulk.

  38. H2S is toxic in large amounts but it’s actually the signaling molecule that you’re trying to introduce. It’s similar to iron and copper – useful in tiny amounts but large amounts translate to heavy metal poisoning. They’re both easily available but you don’t see people munching on steel bars and copper tubing.The toxic impurities I meant are various artifacts of the manufacturing process like heavy metals various other salts and chemicals etc. NaSH is made by reacting NaOH with H2S and older processes could leave mercury traces in the NaOH. Nowadays mercury is less likely but who knows what other contamination there might be in it.One final note: measuring microgram quantities isn’t trivial. Even milligrams require analytical scales. Not something you’d find in an average kitchen.

  39. It doesn’t count if you get her to dress in black leather beforehand.Or maybe it does. My NIH research proposal hasn’t been granted yet.

  40. It’s getting a bit frustrating, isn’t it? Vuukle is radically lacking in features, basically its only selling point is being reliable. And it isn’t even that. Comments keep coming and going.

  41. Technically, you’d find an analytical scale in MY kitchen. Very handy in measuring out small quantities of campden for brewing. I measure micrograms by diluting first.

  42. I’m actually familiar with that, when through chemo once. It’s why I’m pissed off at the fact that I at 240 pounds, and my wife at 80, get prescribed the same dose of antibiotic if we get sick. She gets an upset stomach, and I relapse because it wasn’t enough. Modern medicine is so… crude, they’re not even applying what they know most of the time. It’s a good first approximation, but depending on the specifics about how the liver handles different substances, you can get a huge deviation from it between species. 3g/day of NMN would be a bit too pricey for me. That’s like $120 a week if I buy it bulk.

  43. It’s getting a bit frustrating isn’t it? Vuukle is radically lacking in features basically its only selling point is being reliable.And it isn’t even that. Comments keep coming and going.

  44. Technically you’d find an analytical scale in MY kitchen. Very handy in measuring out small quantities of campden for brewing.I measure micrograms by diluting first.

  45. I’ve been taking the crystalline nicotinamide riboside and pterostilbene product (called Basis) from Elysium for about three years now. Is it keeping me younger? Well, I’m not sure that it’s not. I’m definitely more physically capable that anyone else my age (single digits from retirement) that I know, hike up mountains, ring the bell with the mallet at the carnival, do some Taebo, put the elliptical on max and go as long as I want, etc. On the other hand, like I said, I can’t be entirely sure that it does help, and for me and my wife it’s like $480 a year each.

  46. I’ve been taking the crystalline nicotinamide riboside and pterostilbene product (called Basis) from Elysium for about three years now. Is it keeping me younger? Well I’m not sure that it’s not. I’m definitely more physically capable that anyone else my age (single digits from retirement) that I know hike up mountains ring the bell with the mallet at the carnival do some Taebo put the elliptical on max and go as long as I want etc. On the other hand like I said I can’t be entirely sure that it does help and for me and my wife it’s like $480 a year each.

  47. I took Tru Niagen. If I’m spelling it correctly. They started charging me monthly for it and sending it to me. xD Which, normally, I don’t like. But the benefits were good enough that I let them do it. That specific precursor is called NR (nicotinamide riboside?) and is processed into NMN in the body (I think, apologies if I don’t get that correct).

  48. I took Tru Niagen. If I’m spelling it correctly. They started charging me monthly for it and sending it to me. xD Which normally I don’t like. But the benefits were good enough that I let them do it. That specific precursor is called NR (nicotinamide riboside?) and is processed into NMN in the body (I think apologies if I don’t get that correct).

  49. $480 a year for a supplement is chump change, I’m on SAMe to keep my arthritis at bay, and that’s closer to $600 a year, and I’m probably not taking as much as I should.

  50. $480 a year for a supplement is chump change I’m on SAMe to keep my arthritis at bay and that’s closer to $600 a year and I’m probably not taking as much as I should.

  51. $480 a year for a supplement is chump change, I’m on SAMe to keep my arthritis at bay, and that’s closer to $600 a year, and I’m probably not taking as much as I should.

  52. $480 a year for a supplement is chump change I’m on SAMe to keep my arthritis at bay and that’s closer to $600 a year and I’m probably not taking as much as I should.

  53. I took Tru Niagen. If I’m spelling it correctly. They started charging me monthly for it and sending it to me. xD Which, normally, I don’t like. But the benefits were good enough that I let them do it. That specific precursor is called NR (nicotinamide riboside?) and is processed into NMN in the body (I think, apologies if I don’t get that correct).

  54. I took Tru Niagen. If I’m spelling it correctly. They started charging me monthly for it and sending it to me. xD Which normally I don’t like. But the benefits were good enough that I let them do it. That specific precursor is called NR (nicotinamide riboside?) and is processed into NMN in the body (I think apologies if I don’t get that correct).

  55. I’ve been taking the crystalline nicotinamide riboside and pterostilbene product (called Basis) from Elysium for about three years now. Is it keeping me younger? Well, I’m not sure that it’s not. I’m definitely more physically capable that anyone else my age (single digits from retirement) that I know, hike up mountains, ring the bell with the mallet at the carnival, do some Taebo, put the elliptical on max and go as long as I want, etc. On the other hand, like I said, I can’t be entirely sure that it does help, and for me and my wife it’s like $480 a year each.

  56. I’ve been taking the crystalline nicotinamide riboside and pterostilbene product (called Basis) from Elysium for about three years now. Is it keeping me younger? Well I’m not sure that it’s not. I’m definitely more physically capable that anyone else my age (single digits from retirement) that I know hike up mountains ring the bell with the mallet at the carnival do some Taebo put the elliptical on max and go as long as I want etc. On the other hand like I said I can’t be entirely sure that it does help and for me and my wife it’s like $480 a year each.

  57. It’s getting a bit frustrating, isn’t it? Vuukle is radically lacking in features, basically its only selling point is being reliable. And it isn’t even that. Comments keep coming and going.

  58. It’s getting a bit frustrating isn’t it? Vuukle is radically lacking in features basically its only selling point is being reliable.And it isn’t even that. Comments keep coming and going.

  59. I took Tru Niagen. If I’m spelling it correctly. They started charging me monthly for it and sending it to me. xD Which, normally, I don’t like. But the benefits were good enough that I let them do it. That specific precursor is called NR (nicotinamide riboside?) and is processed into NMN in the body (I think, apologies if I don’t get that correct).

  60. Technically, you’d find an analytical scale in MY kitchen. Very handy in measuring out small quantities of campden for brewing. I measure micrograms by diluting first.

  61. Technically you’d find an analytical scale in MY kitchen. Very handy in measuring out small quantities of campden for brewing.I measure micrograms by diluting first.

  62. I’m actually familiar with that, when through chemo once. It’s why I’m pissed off at the fact that I at 240 pounds, and my wife at 80, get prescribed the same dose of antibiotic if we get sick. She gets an upset stomach, and I relapse because it wasn’t enough. Modern medicine is so… crude, they’re not even applying what they know most of the time. It’s a good first approximation, but depending on the specifics about how the liver handles different substances, you can get a huge deviation from it between species. 3g/day of NMN would be a bit too pricey for me. That’s like $120 a week if I buy it bulk.

  63. I’m actually familiar with that when through chemo once. It’s why I’m pissed off at the fact that I at 240 pounds and my wife at 80 get prescribed the same dose of antibiotic if we get sick. She gets an upset stomach and I relapse because it wasn’t enough. Modern medicine is so… crude they’re not even applying what they know most of the time.It’s a good first approximation but depending on the specifics about how the liver handles different substances you can get a huge deviation from it between species.3g/day of NMN would be a bit too pricey for me. That’s like $120 a week if I buy it bulk.

  64. H2S is toxic in large amounts, but it’s actually the signaling molecule that you’re trying to introduce. It’s similar to iron and copper – useful in tiny amounts, but large amounts translate to heavy metal poisoning. They’re both easily available, but you don’t see people munching on steel bars and copper tubing. The toxic impurities I meant are various artifacts of the manufacturing process, like heavy metals, various other salts and chemicals, etc. NaSH, is made by reacting NaOH with H2S, and older processes could leave mercury traces in the NaOH. Nowadays mercury is less likely, but who knows what other contamination there might be in it. One final note: measuring microgram quantities isn’t trivial. Even milligrams require analytical scales. Not something you’d find in an average kitchen.

  65. H2S is toxic in large amounts but it’s actually the signaling molecule that you’re trying to introduce. It’s similar to iron and copper – useful in tiny amounts but large amounts translate to heavy metal poisoning. They’re both easily available but you don’t see people munching on steel bars and copper tubing.The toxic impurities I meant are various artifacts of the manufacturing process like heavy metals various other salts and chemicals etc. NaSH is made by reacting NaOH with H2S and older processes could leave mercury traces in the NaOH. Nowadays mercury is less likely but who knows what other contamination there might be in it.One final note: measuring microgram quantities isn’t trivial. Even milligrams require analytical scales. Not something you’d find in an average kitchen.

  66. It doesn’t count if you get her to dress in black leather beforehand. Or maybe it does. My NIH research proposal hasn’t been granted yet.

  67. It doesn’t count if you get her to dress in black leather beforehand.Or maybe it does. My NIH research proposal hasn’t been granted yet.

  68. I’ve been taking the crystalline nicotinamide riboside and pterostilbene product (called Basis) from Elysium for about three years now. Is it keeping me younger? Well, I’m not sure that it’s not. I’m definitely more physically capable that anyone else my age (single digits from retirement) that I know, hike up mountains, ring the bell with the mallet at the carnival, do some Taebo, put the elliptical on max and go as long as I want, etc.

    On the other hand, like I said, I can’t be entirely sure that it does help, and for me and my wife it’s like $480 a year each.

  69. It’s getting a bit frustrating, isn’t it? Vuukle is radically lacking in features, basically its only selling point is being reliable.

    And it isn’t even that. Comments keep coming and going.

  70. If you look at the original paper, they word it as the H2S helps boost the main NMN affect, just as exercise does. So do some exercise and you won’t need the H2S. Though I didn’t see that explicitly in the actual results section. Also, the “exercise” was to have the mice run for 20 minutes until exhausted. Where “exhausted” means that a 10 second electric shock wouldn’t get the mice running again. So you need a sadist with a taser to get you doing that daily.

  71. If you look at the original paper they word it as the H2S helps boost the main NMN affect just as exercise does. So do some exercise and you won’t need the H2S.Though I didn’t see that explicitly in the actual results section.Also the exercise”” was to have the mice run for 20 minutes until exhausted. Where “”””exhausted”””” means that a 10 second electric shock wouldn’t get the mice running again. So you need a sadist with a taser to get you doing that daily.”””

  72. The purpose of this research was not to find a human, or even a mouse, treatment. It was rather to investigate the biochemistry in the process. Which means they may well have glossed over issues that are unimportant for their work, but vital for treatment development. For example (and I’m not saying this applies, but it’s just an illustration) if the mice were operating in a diet/genetic/activity level space where they were actually deficient in say vitamin B3, then supplementing would make them more healthy. But doesn’t mean that giving more B3 to a human who is not deficient will help that human.

  73. The purpose of this research was not to find a human or even a mouse treatment. It was rather to investigate the biochemistry in the process.Which means they may well have glossed over issues that are unimportant for their work but vital for treatment development.For example (and I’m not saying this applies but it’s just an illustration) if the mice were operating in a diet/genetic/activity level space where they were actually deficient in say vitamin B3 then supplementing would make them more healthy. But doesn’t mean that giving more B3 to a human who is not deficient will help that human.

  74. I posted a nice long reply which has been eaten. Probably contained too many facts which set off the vuucke defense system. ANYWAY, just go to sci-hub and you can get the paper for free. And the full paper contains useful things like the actual Sigma Aldrich catalog numbers for the various chemicals.

  75. I posted a nice long reply which has been eaten.Probably contained too many facts which set off the vuucke defense system.ANYWAY just go to sci-hub and you can get the paper for free.And the full paper contains useful things like the actual Sigma Aldrich catalog numbers for the various chemicals.

  76. Go to sci-hub and you can get free access to the paper (most papers actually). There is a lot of detail. Such as the H2S being bought from Sigma-Aldrich Cat#161527.

  77. Go to sci-hub and you can get free access to the paper (most papers actually).There is a lot of detail. Such as the H2S being bought from Sigma-Aldrich Cat#161527.

  78. From the abstract at the link “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),” So you get the same effect as H2S by doing exercise. And 80% of the benefit comes from the NMN anyway. The H2S or exercise just boosts the effect a bit. Though the type of exercise isn’t fun, they had the little fellows running to exhaustion over 10 to 40 minutes. And the “To restore NAD+ levels, we administered NMN to 18-month-old mice via drinking water for 2 months at 400 mg/kg/day” which is what I would call a very high dose. It doesn’t scale exactly with mass, but 400 mg/kg/day is about 40 grams/day for me. You guys know you can get the papers for free from sci-hub?

  79. From the abstract at the link 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)”””So you get the same effect as H2S by doing exercise. And 80{22800fc54956079738b58e74e4dcd846757aa319aad70fcf90c97a58f3119a12} of the benefit comes from the NMN anyway. The H2S or exercise just boosts the effect a bit.Though the type of exercise isn’t fun”””” they had the little fellows running to exhaustion over 10 to 40 minutes.And the “”””To restore NAD+ levels”””” we administered NMN to 18-month-old mice via drinking water for 2 months at 400 mg/kg/day”””” which is what I would call a very high dose. It doesn’t scale exactly with mass”””” but 400 mg/kg/day is about 40 grams/day for me.You guys know you can get the papers for free from sci-hub?”””

  80. Much of the time, life extension treatments that work on mice are only bringing things closer to human standards; As soon as you look, you usually find it’s something humans already implement. But, of course, it doesn’t have to be, and sometimes it will be something humans implement fairly well when young, and then do less well as we age.

  81. Much of the time life extension treatments that work on mice are only bringing things closer to human standards; As soon as you look you usually find it’s something humans already implement. But of course it doesn’t have to be and sometimes it will be something humans implement fairly well when young and then do less well as we age.

  82. I’m actually familiar with that, when through chemo once. It’s why I’m pissed off at the fact that I at 240 pounds, and my wife at 80, get prescribed the same dose of antibiotic if we get sick. She gets an upset stomach, and I relapse because it wasn’t enough. Modern medicine is so… crude, they’re not even applying what they know most of the time.

    It’s a good first approximation, but depending on the specifics about how the liver handles different substances, you can get a huge deviation from it between species.

    3g/day of NMN would be a bit too pricey for me. That’s like $120 a week if I buy it bulk.

  83. H2S is toxic in large amounts, but it’s actually the signaling molecule that you’re trying to introduce. It’s similar to iron and copper – useful in tiny amounts, but large amounts translate to heavy metal poisoning. They’re both easily available, but you don’t see people munching on steel bars and copper tubing.

    The toxic impurities I meant are various artifacts of the manufacturing process, like heavy metals, various other salts and chemicals, etc. NaSH, is made by reacting NaOH with H2S, and older processes could leave mercury traces in the NaOH. Nowadays mercury is less likely, but who knows what other contamination there might be in it.

    One final note: measuring microgram quantities isn’t trivial. Even milligrams require analytical scales. Not something you’d find in an average kitchen.

  84. Yes, H2S and NaOH, which is also a problem. I doubt it’s administered directly. It probably needs to be wrapped in something that would control its release, and combined with a buffer or mild acid to neutralize the NaOH afterwards. Probably not a kitchen chemistry project, even if the raw materials are available. Anyway, there’s no such thing as “lab grade”. Depending on chemical, lab suppliers may provide anything from ultra-pure references, through high-purity biology grade, through pharma grade with special manufacturing controls, through food grade (if it’s used in food), through reagent grade (typically 90-99% purity), to cheap technical grade. Depending on regulations, you may need a special license to buy some of these stuff. Generally, the higher the purity, the more regulation, and the lower the sales volume, the more expensive it is. You can go to sigmaaldrich (dot) com, and do a search. They’re one of the major lab chemical suppliers. From what I can see, they currently have one grade of NaSH. Not too expensive, but doesn’t list the purity. It’s probably reagent grade, in which case it may still contain toxic impurities.

  85. Yes H2S and NaOH which is also a problem. I doubt it’s administered directly. It probably needs to be wrapped in something that would control its release and combined with a buffer or mild acid to neutralize the NaOH afterwards. Probably not a kitchen chemistry project even if the raw materials are available.Anyway there’s no such thing as lab grade””. Depending on chemical”” lab suppliers may provide anything from ultra-pure references through high-purity biology grade through pharma grade with special manufacturing controls through food grade (if it’s used in food) through reagent grade (typically 90-99{22800fc54956079738b58e74e4dcd846757aa319aad70fcf90c97a58f3119a12} purity) to cheap technical grade. Depending on regulations you may need a special license to buy some of these stuff. Generally the higher the purity the more regulation and the lower the sales volume the more expensive it is.You can go to sigmaaldrich (dot) com and do a search. They’re one of the major lab chemical suppliers. From what I can see they currently have one grade of NaSH. Not too expensive but doesn’t list the purity. It’s probably reagent grade”” in which case it may still contain toxic impurities.”””

  86. Both NMN and NR are supposed to lead to the same endpoint of NAD+. Like Brett said, there are sometimes reasons to use a precursor further up the chain, and I’ve seen some people make such arguments for NMN, but I don’t think it’s really clear. NR has more human studies, and they are promising. NMN is said to have stronger results than NR… in some rodent studies. It’s newer and has fewer human studies. Both are for sale. Honestly, if either of them will improve your health, the other one probably will too. Just maybe not as much per mg.

  87. Both NMN and NR are supposed to lead to the same endpoint of NAD+. Like Brett said there are sometimes reasons to use a precursor further up the chain and I’ve seen some people make such arguments for NMN but I don’t think it’s really clear. NR has more human studies and they are promising. NMN is said to have stronger results than NR… in some rodent studies. It’s newer and has fewer human studies. Both are for sale. Honestly if either of them will improve your health the other one probably will too. Just maybe not as much per mg.

  88. Senescent cell clearance and generic modification of our mitochondria, so that they produce NAD+, seems to be our best way forward. Unity biotechnology is in phase 1 trials till November and oisin biotechnology starts phase 1 trials in 2019.

  89. Senescent cell clearance and generic modification of our mitochondria so that they produce NAD+ seems to be our best way forward. Unity biotechnology is in phase 1 trials till November and oisin biotechnology starts phase 1 trials in 2019.

  90. If it’s micrograms, you could get lab grade. It’s still dirt cheap. The problem is that it produces H2S on exposure to water. Not rapidly, though. The details of administering it would be interesting. Unfortunately, they’re behind CELL’s paywall.

  91. If it’s micrograms you could get lab grade. It’s still dirt cheap. The problem is that it produces H2S on exposure to water. Not rapidly though. The details of administering it would be interesting. Unfortunately they’re behind CELL’s paywall.

  92. If you look at the original paper, they word it as the H2S helps boost the main NMN affect, just as exercise does. So do some exercise and you won’t need the H2S.
    Though I didn’t see that explicitly in the actual results section.

    Also, the “exercise” was to have the mice run for 20 minutes until exhausted. Where “exhausted” means that a 10 second electric shock wouldn’t get the mice running again. So you need a sadist with a taser to get you doing that daily.

  93. This suggests that senolytics should have similar benefits as these chemical precursors, as a side-effect of reducing senescent cells, in addition to other benefits.

  94. This suggests that senolytics should have similar benefits as these chemical precursors as a side-effect of reducing senescent cells in addition to other benefits.

  95. The purpose of this research was not to find a human, or even a mouse, treatment. It was rather to investigate the biochemistry in the process.

    Which means they may well have glossed over issues that are unimportant for their work, but vital for treatment development.

    For example (and I’m not saying this applies, but it’s just an illustration) if the mice were operating in a diet/genetic/activity level space where they were actually deficient in say vitamin B3, then supplementing would make them more healthy. But doesn’t mean that giving more B3 to a human who is not deficient will help that human.

  96. NaHS converts to H2S, which is toxic (it’s also what contributes to the smell). So I’d imagine you’ll need a very small dose, probably in the micrograms. Certainly not in industrial quantities. I’m guessing the highly available form is technical grade for various industrial uses. That would also have a bunch of impurities which are ok for the industrial use, but not for consumption. What you want is a food supplement in pill form.

  97. NaHS converts to H2S which is toxic (it’s also what contributes to the smell). So I’d imagine you’ll need a very small dose probably in the micrograms. Certainly not in industrial quantities.I’m guessing the highly available form is technical grade for various industrial uses. That would also have a bunch of impurities which are ok for the industrial use but not for consumption. What you want is a food supplement in pill form.

  98. I posted a nice long reply which has been eaten.
    Probably contained too many facts which set off the vuucke defense system.

    ANYWAY, just go to sci-hub and you can get the paper for free.

    And the full paper contains useful things like the actual Sigma Aldrich catalog numbers for the various chemicals.

  99. NMN is a “precursor” for Nicotinamide Riboside, which is to say, it’s what it is made out of. Generally in biology, if you supply more of a precursor, you get more of the end product. Sometimes it’s the better way to approach increasing something, because the desired end product isn’t very bioavailable, or degrades rapidly, or something like that. Anyway, it’s easily available as a supplement, I might give it a try. I don’t think I’ll be trying the sodium hydrosulfide, though. Easily available, but according to the MSDS sheet, it’s corrosive, stinks, and even in low concentrations deadens your sense of smell. Unless the necessary dose is extremely low, I can’t see people using it.

  100. NMN is a precursor”” for Nicotinamide Riboside”” which is to say it’s what it is made out of. Generally in biology if you supply more of a precursor you get more of the end product. Sometimes it’s the better way to approach increasing something because the desired end product isn’t very bioavailable or degrades rapidly or something like that.Anyway it’s easily available as a supplement I might give it a try. I don’t think I’ll be trying the sodium hydrosulfide though. Easily available but according to the MSDS sheet it’s corrosive stinks and even in low concentrations deadens your sense of smell.Unless the necessary dose is extremely low”” I can’t see people using it.”””

  101. Both these are readily available, but sodium hydrosulfide *stinks*. Rotten egg smell. Maybe you can force a mouse to eat it anyway or starve, but as with any aversive treatment, you risk conflating the effect of the compound with calorie deprivation.

  102. Both these are readily available but sodium hydrosulfide *stinks*. Rotten egg smell.Maybe you can force a mouse to eat it anyway or starve but as with any aversive treatment you risk conflating the effect of the compound with calorie deprivation.

  103. Go to sci-hub and you can get free access to the paper (most papers actually).

    There is a lot of detail. Such as the H2S being bought from Sigma-Aldrich Cat#161527.

  104. From the abstract at the link “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),”

    So you get the same effect as H2S by doing exercise. And 80% of the benefit comes from the NMN anyway. The H2S or exercise just boosts the effect a bit.

    Though the type of exercise isn’t fun, they had the little fellows running to exhaustion over 10 to 40 minutes.

    And the “To restore NAD+ levels, we administered NMN to 18-month-old mice via drinking water for 2 months at 400 mg/kg/day” which is what I would call a very high dose. It doesn’t scale exactly with mass, but 400 mg/kg/day is about 40 grams/day for me.

    You guys know you can get the papers for free from sci-hub?

  105. Much of the time, life extension treatments that work on mice are only bringing things closer to human standards; As soon as you look, you usually find it’s something humans already implement.

    But, of course, it doesn’t have to be, and sometimes it will be something humans implement fairly well when young, and then do less well as we age.

  106. Is this going to work in humans in the same way as in mice? That is always really hard to tell. Do mice, which live 2-3 years in captivity, experience the same intrinsic damage to their mitochondrial DNA as humans do over 70-80 years? Is the extrinsic damage which affects mitochondrial function over time the same in mice and humans? w­ww.fightaging.o­rg/archives/2006/10/how-age-damaged-mitochondria-cause-your-cells-to-damage-you/ Lifespan.io/Leafscience are going to carry out a fundraiser for another David Sinclair lab study on boosting NAD+ levels in mice. More data and repeating experiments is always good. But I wonder if the results and model will actually tell us much about humans. I also wonder how much it would cost to set up a tiny phase 1 human trial? [As an aside, is it just me who finds that Leafscience.o­rg having a different name Lifespan.i­o for their crowdfunding a confusion? I think the name Lifespan.i­o is better as it is more descriptive of what they do, so they should just switch to using that everywhere and drop the legacy leafscience name.]

  107. Is this going to work in humans in the same way as in mice? That is always really hard to tell. Do mice which live 2-3 years in captivity experience the same intrinsic damage to their mitochondrial DNA as humans do over 70-80 years? Is the extrinsic damage which affects mitochondrial function over time the same in mice and humans?w­ww.fightaging.o­rg/archives/2006/10/how-age-damaged-mitochondria-cause-your-cells-to-damage-you/Lifespan.io/Leafscience are going to carry out a fundraiser for another David Sinclair lab study on boosting NAD+ levels in mice. More data and repeating experiments is always good. But I wonder if the results and model will actually tell us much about humans.I also wonder how much it would cost to set up a tiny phase 1 human trial?[As an aside is it just me who finds that Leafscience.o­rg having a different name Lifespan.i­o for their crowdfunding a confusion? I think the name Lifespan.i­o is better as it is more descriptive of what they do so they should just switch to using that everywhere and drop the legacy leafscience name.]”

  108. Can someone tell me how this varies from Nicotinamide Riboside? Also: is this going to work the same way in humans as in mice? Can we take it now? If not now, when? Did the mice .. live any longer?

  109. Can someone tell me how this varies from Nicotinamide Riboside?Also: is this going to work the same way in humans as in mice? Can we take it now? If not now when? Did the mice .. live any longer?

  110. So, I’m only thirty-five, but I began working a desk job a few years ago, which has, sadly, led to a decrease in health. I’m finally turning that around, but when I began taking an NAD+ precursor, I did notice an increase in my ability to exercise, and a decrease in muscle ache and joint pain. In fact, the joint pains I had felt in my knees for almost fifteen years pretty much vanished. My vision did improve (albeit only slightly, so I can’t peg the precursor for that), and my body can sustain longer periods of physical activity, near or even above levels which I could sustain when I was working at Starbucks for approximately seven years and was constantly in my feet. That’s something quite significant, to me. Also, I can dance longer at anime convention raves (take that as you will >_> ) drinking only water and no coffee, which is a major improvement. What I mean by that, is that I don’t require as much caffeine, i.e. stimulant, to sustain healthy energy levels. I’m not saying go out and buy an NAD+ precursor, since I’m not at the age at which I should really need one, myself, and everyone’s body is different. But I did notice improvements. Personal anecdote, but there it is.

  111. So I’m only thirty-five but I began working a desk job a few years ago which has sadly led to a decrease in health. I’m finally turning that around but when I began taking an NAD+ precursor I did notice an increase in my ability to exercise and a decrease in muscle ache and joint pain. In fact the joint pains I had felt in my knees for almost fifteen years pretty much vanished. My vision did improve (albeit only slightly so I can’t peg the precursor for that) and my body can sustain longer periods of physical activity near or even above levels which I could sustain when I was working at Starbucks for approximately seven years and was constantly in my feet. That’s something quite significant to me. Also I can dance longer at anime convention raves (take that as you will >_> ) drinking only water and no coffee which is a major improvement. What I mean by that is that I don’t require as much caffeine i.e. stimulant to sustain healthy energy levels. I’m not saying go out and buy an NAD+ precursor since I’m not at the age at which I should really need one myself and everyone’s body is different. But I did notice improvements. Personal anecdote but there it is.

  112. Yes, H2S and NaOH, which is also a problem. I doubt it’s administered directly. It probably needs to be wrapped in something that would control its release, and combined with a buffer or mild acid to neutralize the NaOH afterwards. Probably not a kitchen chemistry project, even if the raw materials are available.

    Anyway, there’s no such thing as “lab grade”. Depending on chemical, lab suppliers may provide anything from ultra-pure references, through high-purity biology grade, through pharma grade with special manufacturing controls, through food grade (if it’s used in food), through reagent grade (typically 90-99% purity), to cheap technical grade. Depending on regulations, you may need a special license to buy some of these stuff. Generally, the higher the purity, the more regulation, and the lower the sales volume, the more expensive it is.

    You can go to sigmaaldrich (dot) com, and do a search. They’re one of the major lab chemical suppliers. From what I can see, they currently have one grade of NaSH. Not too expensive, but doesn’t list the purity. It’s probably reagent grade, in which case it may still contain toxic impurities.

  113. Inflammation may also be caused by AGEs (Advanced glycation end-products). The formation of AGEs can be reduced by Metformin, Pyridoxal-5-phosphate (P-5-P), L Carnosine, and Benfotiamine.

    And reduced dietary intake of AGEs may also reduce levels, but apparently there is still debate on that. That can be done by using avocado oil, corn oil, safflower oil, and sunflower oil. Pistachio oil is probably good too. Most of the nuts have a lot of AGEs…but pistachios seem to be ok. You want cold pressed oils and definitely not roasted oils. And avoid olive oil, peanut oil, sesame oil and canola oil. And cooking everything that you cook at low temperatures: no grilling, frying, or roasting. Avoid butter, any kind of fried potato and bacon especially. Avoid things that are beaten: butter, mayonnaise, various sauces. High temperature and beating generates these things. Acid can dramatically reduce the formation, so marinating before cooking is good. But you can’t just put something acidic on the food after you cooked it. It must be between the cooking surface and the food.
    Boiled, stewed or microwaved is best.

    Search: “Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet”

  114. Both NMN and NR are supposed to lead to the same endpoint of NAD+. Like Brett said, there are sometimes reasons to use a precursor further up the chain, and I’ve seen some people make such arguments for NMN, but I don’t think it’s really clear. NR has more human studies, and they are promising. NMN is said to have stronger results than NR… in some rodent studies. It’s newer and has fewer human studies. Both are for sale.

    Honestly, if either of them will improve your health, the other one probably will too. Just maybe not as much per mg.

  115. Senescent cell clearance and generic modification of our mitochondria, so that they produce NAD+, seems to be our best way forward. Unity biotechnology is in phase 1 trials till November and
    oisin biotechnology starts phase 1 trials in 2019.

  116. If it’s micrograms, you could get lab grade. It’s still dirt cheap. The problem is that it produces H2S on exposure to water. Not rapidly, though.

    The details of administering it would be interesting. Unfortunately, they’re behind CELL’s paywall.

  117. This suggests that senolytics should have similar benefits as these chemical precursors, as a side-effect of reducing senescent cells, in addition to other benefits.

  118. NaHS converts to H2S, which is toxic (it’s also what contributes to the smell). So I’d imagine you’ll need a very small dose, probably in the micrograms. Certainly not in industrial quantities.

    I’m guessing the highly available form is technical grade for various industrial uses. That would also have a bunch of impurities which are ok for the industrial use, but not for consumption. What you want is a food supplement in pill form.

  119. NMN is a “precursor” for Nicotinamide Riboside, which is to say, it’s what it is made out of. Generally in biology, if you supply more of a precursor, you get more of the end product. Sometimes it’s the better way to approach increasing something, because the desired end product isn’t very bioavailable, or degrades rapidly, or something like that.

    Anyway, it’s easily available as a supplement, I might give it a try. I don’t think I’ll be trying the sodium hydrosulfide, though. Easily available, but according to the MSDS sheet, it’s corrosive, stinks, and even in low concentrations deadens your sense of smell.

    Unless the necessary dose is extremely low, I can’t see people using it.

  120. Both these are readily available, but sodium hydrosulfide *stinks*. Rotten egg smell.

    Maybe you can force a mouse to eat it anyway or starve, but as with any aversive treatment, you risk conflating the effect of the compound with calorie deprivation.

  121. Is this going to work in humans in the same way as in mice?

    That is always really hard to tell. Do mice, which live 2-3 years in captivity, experience the same intrinsic damage to their mitochondrial DNA as humans do over 70-80 years? Is the extrinsic damage which affects mitochondrial function over time the same in mice and humans?

    w­ww.fightaging.o­rg/archives/2006/10/how-age-damaged-mitochondria-cause-your-cells-to-damage-you/

    Lifespan.io/Leafscience are going to carry out a fundraiser for another David Sinclair lab study on boosting NAD+ levels in mice. More data and repeating experiments is always good. But I wonder if the results and model will actually tell us much about humans.

    I also wonder how much it would cost to set up a tiny phase 1 human trial?

    [As an aside, is it just me who finds that Leafscience.o­rg having a different name Lifespan.i­o for their crowdfunding a confusion? I think the name Lifespan.i­o is better as it is more descriptive of what they do, so they should just switch to using that everywhere and drop the legacy leafscience name.]

  122. Good article from Steve Hill of Leafscience on NAD+, and why it declines with age:

    w­ww.leafscience.o­rg/nad-and-aging/

    “We now know that CD38 is the major culprit in NAD+ decline, but why does it fall in the first place? CD38 expression and activity are known to be induced by inflammatory cytokines and bacterial endotoxins, such as lipopolysaccharides (LPS) [8-11]. This strongly suggests that the smouldering, age-related, chronic inflammation commonly called “inflammaging” may be driving the increased expression of CD38 and the resulting NAD+ decline.

    This is because senescent cells secrete CD38 as part of the pro-inflammatory cytokine cocktail known as the senescence-associated secretory phenotype (SASP). This mixture of pro-inflammatory signals includes CD38, and senescent cells accumulate during aging as the immune system increasingly fails to remove the problem cells. Thus, more senescent cells almost certainly means more CD38 and less NAD+ available.

    The same goes for increasing amounts of cell debris and microbial burden; these also drive inflammaging, thus increasing CD38, decreasing NAD+, and causing age-related dysfunction.”

  123. Can someone tell me how this varies from Nicotinamide Riboside?

    Also: is this going to work the same way in humans as in mice? Can we take it now? If not now, when? Did the mice .. live any longer?

  124. So, I’m only thirty-five, but I began working a desk job a few years ago, which has, sadly, led to a decrease in health. I’m finally turning that around, but when I began taking an NAD+ precursor, I did notice an increase in my ability to exercise, and a decrease in muscle ache and joint pain. In fact, the joint pains I had felt in my knees for almost fifteen years pretty much vanished. My vision did improve (albeit only slightly, so I can’t peg the precursor for that), and my body can sustain longer periods of physical activity, near or even above levels which I could sustain when I was working at Starbucks for approximately seven years and was constantly in my feet. That’s something quite significant, to me. Also, I can dance longer at anime convention raves (take that as you will >_> ) drinking only water and no coffee, which is a major improvement. What I mean by that, is that I don’t require as much caffeine, i.e. stimulant, to sustain healthy energy levels. I’m not saying go out and buy an NAD+ precursor, since I’m not at the age at which I should really need one, myself, and everyone’s body is different. But I did notice improvements. Personal anecdote, but there it is.

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