31 replies to this topic

[MikeDC]

This review paper is written by scientists in National Institute of Aging at NIH. It feels that they are declaring that they have solved the aging puzzle.

https://www.ncbi.nlm...from=nad aging

[Daniel Cooper]

I think that anyone that claims to have "solved the aging puzzle" is misinformed.  

 

I don't doubt that NAD+ depletion is a factor in aging.  But, we know it's not the only factor.  The build up of senolytic cells and AGEs are also significant (likely more prominent) factors that play in to aging.  

 

As Josh Mittledorf suggests, we're designed to age.  It's part of the program.  It makes sense from an evolutionary point of view that organisms would be designed to have a finite lifespan.  I think we'll see a fair amount of progress over the next couple of decades in overcoming these built in limits (and NR may well be a part of that) and eventually we'll be able to change the underlying program itself, but it is going to take action on many different fronts to make progress.  

 

I do think that overcoming mitochondrial dysfunction, removing senescent cells, and breaking up AGEs are likely to be the things that yield the most benefit in the near term.

 

I didn't see anything that blew my socks off in the abstract to the above paper.  Can anyone post the entire text?

 

 

[MikeDC]

NAD+ depletion is probably the most significant factor in aging and age related diseases. Senescent cells and glycation are implantant too. But the damage from senescent cells is also reflected through depleting NAD+. NAD+ can also rejuvenate senescent cells and prevent normal cells from becoming senescent. NAD+ depletion is very important and easy to correct with precursors like Vitamin B3. Nicotinamide Riboside is the most potent at inducing Sirt1 expression. It is a mimic of exercise and calorie restriction. Exercise and calorie restriction will not be very effective for old people because the baseline NAD+ reduces with age.

[Daniel Cooper]

Have you seen the before an after pictures of the study mice from the FOX04-DRI study?  I haven't seen anything from an NR study that looked as dramatic.  

 

I'm convinced that NAD+ depletion is a big deal.  I just question whether it is the biggest deal.

 

 

 

[MikeDC]

Read the personal experience thread. NR works on humans. I am a good example of it. Lost 20lbs, lowered cholesterol, cured prediabetes, cure prostate inflammation and pain. My skin is smoother than I was at 20 year old.

I am watching the progress on senolytics. I don't think we have as a good solution as in NAD+ depletion. Even Foxo4-Dri kills 12 normal cells per senescent cell. So it is not specific.

[Daniel Cooper]

I used NR for a couple of years.  I'm currently off it because I'm sorting though some other health issue (high hemoglobin) and I want to make sure that NR isn't clouding the picture.  I hope to be back to using it in a few months.  

 

I actually have some neuropathy and it didn't cure that, but I do believe it lowered my average blood glucose level from about 100 to 70ish.  I can't be certain about that as I haven't run a controlled experiment but that is my sense of the reduction I got.

 

On the FOX04-DRI - I would be very much surprised if it killed 12 normal cells for every senescent cell, in fact I would suggest it was the reverse knowing the MOA.  Are you sure about those numbers?

 

 

 

[MikeDC]

I read a paper that references the original article and said the original article reported the ratio as 12 to 1. Other senolytics papers don't report it and believed to be much worse.

Niagen almost cured my prostate inflammation and pain. But I am not sure it is by coincidence or not, I tried a few days of GHRH and GHRP mixture and that seemed to cleared up the pain completely. It could have helped the nerve repair.

[Michael]

As Josh Mittledorf suggests, we're designed to age. It's part of the program. It makes sense from an evolutionary point of view that organisms would be designed to have a finite lifespan.

Actually, it would make no senscent all from an evolutionary point of view for organisms to be designed to have a finite lifespan; indeed, it's counter to the very nature of natural selection, which acts on the phenotype of the individual organism. See here for instance.
 

I didn't see anything that blew my socks off in the abstract to the above paper. Can anyone post the entire text?

I've read the paper. It doesn't make anything like the kind of outlandish claim that MikeDC is attributing to it.
 

Read the personal experience thread. NR works on humans. I am a good example of it. Lost 20lbs, lowered cholesterol, cured prediabetes, cure prostate inflammation and pain. My skin is smoother than I was at 20 year old.

Your anecdotal experience is not matched by the vast majority of users, even in the anecdotal self-selected self-reports on the personal experience thread. IAC, even what you report pales before the effects of senolytic therapies in normally-aging rodents.
 

I am watching the progress on senolytics. I don't think we have as a good solution as in NAD+ depletion. Even Foxo4-Dri kills 12 normal cells per senescent cell. So it is not specific.

You're reading this backward. Per the original report, "FOXO4-DRI to potently and selectively (11.73-fold difference) reduce the viability of senescent versus control IMR90 (Figure 3A) and other normal cells (Figure S3A)." Ie, FOXO4-DRI is about twelve times more likely to kill senescent versus normal cells, at least in vitro. Certainly, if it was killing twelve times as many healthy cells as normal, it would be ravaging these animals instead of seemingly rescuing them.
 
Daniel Cooper wrote: Have you seen the before an after pictures of the study mice from the FOX04-DRI study?  I haven't seen anything from an NR study that looked as dramatic.
 
Careful with those, however. The photos, and most of the pop press, focused on purportedly "premature aging" mice, which is a petitio principii; there is only a very small (though still promising) amount of short-term data on wild-type mice. However, the work with senolytic drugs and the preliminary work with Oisín's genetic-based senlolytic agents is extremely clear and impressive.

[MikeDC]

Sinclair produced some shocking pictures of mouse comparisons from Ubiquinol and Resveratrol. They are beneficial to human health. But their effects are hard to notice. On the other hand, a large percentage of people who tried Niagen can swear for the anti aging effects of NR. I have tried many supplements including Resveratrol and Ubiquinol, none of them had any effect on me that I can feel and see. NR is 100x better than both adding together.

Actually i have used Ubiquinol continuously for 10 years. My skin changed to super smooth after only 2 weeks of Niagen. My skin is smoother now when I am close to 60 than I was at 20 year old.  IMG_2814.JPG   18.57KB   7 downloads

Edited by MikeDC, 01 October 2017 - 06:03 PM.

[Daniel Cooper]

Sinclair produced some shocking pictures of mouse comparisons from Ubiquinol and Resveratrol. They are beneficial to human health. But their effects are hard to notice. On the other hand, a large percentage of people who tried Niagen can swear for the anti aging effects of NR. I have tried many supplements including Resveratrol and Ubiquinol, none of them had any effect on me that I can feel and see. NR is 100x better than both adding together.

Actually i have used Ubiquinol continuously for 10 years. My skin changed to super smooth after only 2 weeks of Niagen. My skin is smoother now when I am close to 60 than I was at 20 year old.IMG_2814.JPG

 

Smoother?  In what way?

 

I'll bet my house that your skin isn't less wrinkled at 60 than it was at 20 no matter what you're taking.

 

And I don't believe anyone that tells me that they note obvious skin differences in two weeks taking anything orally.  The epidermal layer just don't turn over fast enough to see those sorts of effects that fast.

[Heisok]

MikeDC it is great that you cured prediabetes with NR, congratulations. Now that is 2 cases so far which you have reported with Diabetes or pre-Diabetes. By your report, the second had to go on Insulin in spite of being on NR at the very least similar doses to you plus Metformin. Proving pre-Diabetes curing is one thing, but Insulin is a serious choice for an individual to have to make. I hope they do well.

 

As far as your Prostate. Congratulations once again. Adding NR to my regiment had no noticeable effect for my BPH in spite of taking it for over a year in addition to a prostate formula which had up until then prevented further increases in size, but had eliminated partial voiding which resulted in too many small urinations throughout the day, and during the sleep hours. Another member who had been taking fairly large doses of NR mentioned that only after adding Honokiol were they able to go off a medication. Seeing that, and adding Honokiol for other reasons at bedtime, I  noticeably SHRANK my Prostate. (I did not think that could happen, nor had actual shrinking been mentioned by the other member.)

 

P.S. I believe NR has benefits.

 

 

 

 

Edited by Heisok, 01 October 2017 - 06:58 PM.

[Daniel Cooper]

Micheal -

 

I disagree with you that it makes no sense for organisms to be designed with a finite lifespan from an evolutionary sense.  I think it makes eminent sense.

 

1.) Evolution isn't concerned with the preservation of a particular organism, it is concerned with the preservation of a genome. It doesn't care one wit if you are around, only your genetic material.

 

2.) Given that evolution operates at the genome level and not the organism level, there are macro concerns such as the danger of population crash/extinction due to overpopulation in times of scare resources that will certainly tend to favor having finite lifespans. You die off so that population doesn't grow unbounded so that your progeny live.

 

3.) Evolution is all about adaption in the face of a changing environment.  Existing population don't adapt from an evolutionary point of view as their genome is fixed.  It is the constant culling of population and the fact that only the more adapted organisms hang around to breed the next generation that makes evolution work. Because of the danger of crashes due to population (issue 2), the only organisms that have practically unlimited lifespans are things such as giant redwoods which reproduce very slowly.  But, as we can see from those examples, they haven't been very successful at adapting to environmental changes because of the slow rate at which new generations are produced.  So there's a trade off there between lifespan and adaptability. 

 

I think is obvious that having built in finite limits on lifespan is an evolutionary adaptation.  Now, that doesn't mean that we won't work around these limits, I'm certain we will though much less certain that I'll be around to see it.

 

 

[MikeDC]

Sinclair produced some shocking pictures of mouse comparisons from Ubiquinol and Resveratrol. They are beneficial to human health. But their effects are hard to notice. On the other hand, a large percentage of people who tried Niagen can swear for the anti aging effects of NR. I have tried many supplements including Resveratrol and Ubiquinol, none of them had any effect on me that I can feel and see. NR is 100x better than both adding together.

Actually i have used Ubiquinol continuously for 10 years. My skin changed to super smooth after only 2 weeks of Niagen. My skin is smoother now when I am close to 60 than I was at 20 year old.IMG_2814.JPG

Smoother? In what way?

I'll bet my house that your skin isn't less wrinkled at 60 than it was at 20 no matter what you're taking.

And I don't believe anyone that tells me that they note obvious skin differences in two weeks taking anything orally. The epidermal layer just don't turn over fast enough to see those sorts of effects that fast.

Don't be so sure. The effects from NR differs between people based on difference in genes. I would have to say I am the most sensitive to NR among all friends taking NR. Cells on the skin don't need to turn over to get the effects of NR. All your cells are rejuvenated after NAD+ is increased. Smoother skins just mean that skin cells are functioning like young cells. I have never said NR can remove wrinkles. I don't have any wrinkles anyway.

[Daniel Cooper]

Actually i have used Ubiquinol continuously for 10 years. My skin changed to super smooth after only 2 weeks of Niagen. My skin is smoother now when I am close to 60 than I was at 20 year old.IMG_2814.JPG

Smoother? In what way?

I'll bet my house that your skin isn't less wrinkled at 60 than it was at 20 no matter what you're taking.

And I don't believe anyone that tells me that they note obvious skin differences in two weeks taking anything orally. The epidermal layer just don't turn over fast enough to see those sorts of effects that fast.

Don't be so sure. The effects from NR differs between people based on difference in genes. I would have to say I am the most sensitive to NR among all friends taking NR. Cells on the skin don't need to turn over to get the effects of NR. All your cells are rejuvenated after NAD+ is increased. Smoother skins just mean that skin cells are functioning like young cells. I have never said NR can remove wrinkles. I don't have any wrinkles anyway.

 
So your skin is smoother than it was at 20 and you don't have any wrinkles?
 
So, you look like a 20 year old at 60?
 
We really need to see some pictures of that.

Edited by Michael, 04 October 2017 - 04:07 PM.
trim quotes

[MikeDC]

MikeDC it is great that you cured prediabetes with NR, congratulations. Now that is 2 cases so far which you have reported with Diabetes or pre-Diabetes. By your report, the second had to go on Insulin in spite of being on NR at the very least similar doses to you plus Metformin. Proving pre-Diabetes curing is one thing, but Insulin is a serious choice for an individual to have to make. I hope they do well.

As far as your Prostate. Congratulations once again. Adding NR to my regiment had no noticeable effect for my BPH in spite of taking it for over a year in addition to a prostate formula which had up until then prevented further increases in size, but had eliminated partial voiding which resulted in too many small urinations throughout the day, and during the sleep hours. Another member who had been taking fairly large doses of NR mentioned that only after adding Honokiol were they able to go off a medication. Seeing that, and adding Honokiol for other reasons at bedtime, I noticeably SHRANK my Prostate. (I did not think that could happen, nor had actual shrinking been mentioned by the other member.)

P.S. I believe NR has benefits.

Just taking NR at moderate doses may not be enough to cure prediabetes.
It only occurred after I have lost 20lbs and eat very little carb.
I think the power of NR is mostly in its ability to maintain normal metabolism and
Epigenetics. This slows down aging and reduces the risk of age related diseases.
So some people will be disappointed NR doesn't cure all their problems.
NR rewards people who take it early in life and don't expect a miracle short term.

[MikeDC]

 

Actually i have used Ubiquinol continuously for 10 years. My skin changed to super smooth after only 2 weeks of Niagen. My skin is smoother now when I am close to 60 than I was at 20 year old.IMG_2814.JPG

Smoother? In what way?

I'll bet my house that your skin isn't less wrinkled at 60 than it was at 20 no matter what you're taking.

So your skin is smoother than it was at 20 and you don't have any wrinkles?

So, you look like a 20 year old at 60?

We really need to see some pictures of that.

 

I don't look like a 20 year old. The skin damage from the Sun on the face is hard to prevent and reverse. The smoothness is from the sebum that skin cells secrets. NR has made my skin cells to secrete lots of sebum that is more than when I was young. It feels much softer also. I compared my inner wrist skin with a 20 year old and my skin looks better.

Edited by Michael, 04 October 2017 - 04:09 PM.
trim quotes

[Heisok]

Great reply Mike!

 

"Just taking NR at moderate doses may not be enough to cure prediabetes.
It only occurred after I have lost 20lbs and eat very little carb.
I think the power of NR is mostly in its ability to maintain normal metabolism and
Epigenetics. This slows down aging and reduces the risk of age related diseases.
So some people will be disappointed NR doesn't cure all their problems.
NR rewards people who take it early in life and don't expect a miracle short term."

[Michael]

Sinclair produced some shocking pictures of mouse comparisons from Ubiquinol and Resveratrol. They are beneficial to human health. But their effects are hard to notice. On the other hand, a large percentage of people who tried Niagen can swear for the anti aging effects of NR. I have tried many supplements including Resveratrol and Ubiquinol, none of them had any effect on me that I can feel and see. NR is 100x better than both adding together.

Actually i have used Ubiquinol continuously for 10 years. My skin changed to super smooth after only 2 weeks of Niagen. My skin is smoother now when I am close to 60 than I was at 20 year old.IMG_2814.JPG

 
The mice in photos you link (without citation, but which are the same photos posted on Life Extension's website) are notnormal mice, and the effect of ubiquinol in these animals doesn't tell us anything about its effects in otherwise-normal aging mice or humans. These are so-called "senescence-accelerated prone" SAMP1 mice. These mice are subject to severe oxidative stress and therefore develop pathologies superficially similar to "normal" degenerative aging at very young ages: the oldest mice in the series you post are 12 months old, which is still young adulthood in normal mice. Unsurprisingly, if you have a mouse that suffers from severe oxidative stress, giving it antioxidants (carnosine, resveratrol, ubiquinol, NAC ... practically anything would probably do) partially normalizes its miserably-short life. But that doesn't tell you anything about whether these supplements are beneficial in "normal" aging.
 
This is also not a Sinclair study, but an internal study from the Japanese manufacturer of ubiquinol.
 
Do you indeed have similar photos (from S or anyone else) of resveratrol in normally-aging mice? My guess is you're thinking of his photos of resveratrol-supplemented diabetic, obese, high-fat/high-sugar fed mice, which is again not valid evidence for its effects in "normal" aging.
 
 

Micheal -
 
I disagree with you that it makes no sense for organisms to be designed with a finite lifespan from an evolutionary sense.  I think it makes eminent sense.
 
1.) Evolution isn't concerned with the preservation of a particular organism, it is concerned with the preservation of a genome. It doesn't care one wit if you are around, only your genetic material.

Speaking of evolution in this anthropomorphic/teleological way can be a convenient shorthand, but it has the danger of leading one's thinking astray. Remember, evolution isn't a "thing," and it doesn't "care" about anything — either the preservation of a particular organism, or the preservation of a genome. Evolution happens, as a process, because there is genetic variation in the population, and that genetic variation is manifest in in a given organism by a corresponding phenotype. In a given environment, that phenotype will have greater or lesser chances of leaving behind viable offspring (meaning not just viable at birth, but the longer-term viability  of surviving into adulthood, feeding itself, and reproducing in turn). The genes that generate organisms that that leave behind more viable offspring are preserved in those organisms' germ line; those genes that help generate organisms that that leave behind more fewer viable offspring are not thus preserved. As a result, some genes spread, and some genes wither.
 
Of course, I know you know this already. But bear it in mind below.
 
So:
 

2.) Given that evolution operates at the genome level and not the organism level, there are macro concerns such as the danger of population crash/extinction due to overpopulation in times of scare resources that will certainly tend to favor having finite lifespans. You die off so that population doesn't grow unbounded so that your progeny live.

First: populations crash all the time: deer, mice, locusts, etc. There is no evidence for a mechanism to avoid it outside of single-shared organisms with extensive horizontal gene transfer. This follows naturally out of the mechanism of natural selection, which operates at the level of the phenotype of the individual organism bearing a given gene.
 
Second, and relatedly: evolution actually does operate at the organism level and not the genome level (above) — and, more importantly, it happens at the individual organism level, not at the level of a population or a species. You're pointing to a "collective action problem," but unlike in the Prisoner's Dilemma, there is no higher mind or conscience or outside judge to intervene in the purely mechanical process of natural selection for genes that yield individual organisms with phenotypes that lead those genes to be passed on.

The suggested benefits from aging are ones that serve the interests of the species or group. Whenever a benefit at the group level is assumed to supersede the contrary interests of the individual, any evolutionary hypothesis must confront the problem of “cheating.” Individuals in whom the aging program was inactivated by mutation would benefit from the sacrifice of others, while enjoying any fitness advantage that might accrue from immortality. Such mutations would therefore be expected to spread. ...
 
(1) Data on age-related mortality patterns in wild animal populations reveal that, in many species, individuals rarely survive to ages when senescent deterioration becomes apparent (Medawar, 1952; Lack, 1954; Finch, 1990). For most natural populations, extrinsic mortality (due to accidents, predation, starvation, disease, cold, etc.) is such that death occurs well before “old age.” This means that (a) there is no requirement for aging to weed out “worn-out individuals”; b) there is no evidence that aging in fact serves as a significant mortality force in the wild; and © there can have been scant opportunity to evolve genes specifically for aging, even if they were beneficial, since natural selection would not normally “see” them in action. ...
 
Although attempts have been made theoretically to explore the evolution of programmed aging and death in spatially structured populations (e.g., Travis %5B2004%5D), no convincing arguments have been advanced to support the general evolution of aging through such a mechanism.If the theoretical arguments against programmed aging are felt to be insufficient, compelling as they are, it is noteworthy that, although hundreds of mutations have been found to extend longevity in C. elegans, no combination of mutations has yet been found which abolishes aging altogether. From a purely empirical standpoint, this suggests either that the program for aging is extraordinarily robust or that it does not exist.
 
Understanding the Odd Science of Aging
Thomas B.L.Kirkwood

 

3.) Evolution is all about adaption in the face of a changing environment.  Existing population don't adapt from an evolutionary point of view as their genome is fixed.  It is the constant culling of population and the fact that only the more adapted organisms hang around to breed the next generation that makes evolution work. [...] So there's a trade off there between lifespan and adaptability.

You're again falling into the trap of thinking about evolution as a "thing" that happens outside of the mechanistic process of evolution. Evolution allows species to be adaptable, but it doesn't make individual organisms or their individual genomes adaptable. When the environment changes, the species is adaptable because different organisms with different genes suddenly gain this advantage instead — but this happens at the level of survival and reproduction of the individual organism bearing its individual genes. The genes of successful organisms are no more "adaptable" than those of unsuccessful organisms: they are the ones that generate phenotypes that allow for survival and reproduction of the individual organism in that environment. When the environment changes, they don't adapt: their genes are fixed! But the species adapts, because even as one set of genes continues to generate individual organisms that fail to thrive, another set of genes generates individual organisms that do thrive. Neither winner nor loser is "adaptable," and neither has "adaptability genes." Variation between non-adaptable genomes gives adaptability to the species as a whole.

 
Many advocates of programmed aging propose that a species which ages has a selection advantage because it evolves faster. For example, Skulachev (1997) wrote: Death caused by aging clears the population of ancestors and frees space for progeny carrying new useful traits. This is reminiscent of Weismann's idea, to which Skulachev referred. The difference is that, according to Skulachev, aging removes otherwise perfectly healthy individuals from the population in the hope that this is compensated by newborns carrying advantageous mutations. The problem with this idea is that most mutations are deleterious, so the next generation is not automatically better adapted. In the absence of aging (which must be assumed to be the original state, if the theory is not to be circular), it is not clear how Skulachev's death mechanism can actually target ‘ancestors’. Even if it could, removal of chronologically old individuals would be a process that selectively eliminates organisms of higher average fitness, because survival to higher ages would on average be a sign that the individual was endowed with a genotype of above-average fitness. Skulachev did not propose any quantitative justification of his hypothesis, and on closer examination, it would seem that if one were to follow his argument, this would lead to the unintended consequence that aging actually delays evolution by selective removal of individuals with high intrinsic fitness.
 
Can aging be programmed? A critical literature review

• 
  
• Axel Kowald and Thomas B. L. Kirkwood

 

[Daniel Cooper]

Michael,

 

 

If there are no inherent limits to lifespan "designed" by the evolutionary process to almost every organism and the only practical limits to lifespan are due to pathological elements in the environment (e.g. tigers, falling off cliffs, radiation, various toxins, etc) then why don't we have evidence of statistical outliers that manage to avoid these pathological elements and live to significantly greater ages?

 

There are after all 7.4 billion humans on the planet.  If only 0.001% manage to avoid the things that kill 99.999% of us, you should have 74,000 unusually old people .... say perhaps a few hundred years old.  Instead, what we see is that average lifespans in the West tend to hover around the late 70s with mere handful of people living 50% longer than that to about 120.  That sort of clustering of lifespans implies that it is part of the program and not simply environmental elements.

 

If someone could show me some very fortunate 300 year old humans I'd tend to believe that a finite lifespan was not part of our genomic program, but the available evidence seems to point in the other direction.  

 

-Dan

 

 

Edited by Daniel Cooper, 04 October 2017 - 07:44 PM.

[MikeDC]

Let's wait and see if NR can break the 120 barrier significantly.

[Daniel Cooper]

Another way to look at this is this:

 

Postulate:  Human lifespan is not genetically limited.  Lifespan is dictated by the occurrence of randomly distributed external pathologies such as predation, accident, infection, radiological factors, and environmental toxins.

 

Question:  What would a distribution of lifespans look like given the above postulate?

 

Well, what you would expect is some sort of Gaussian distribution with a hard limit on the left at zero (can't die before you're born) and a long tail with no hard limit on the right hand side. 

 

Question:  What do we actually see?

 

The left hand side is in good agreement with our proposal, but as we move to the right we find an absolutely hard limit at 122 years, 164 days.  There is no person in history recorded to have lived longer than Jeanne Louise Calment.  This not the sort of lifespan distribution I would expect if there were not genomic limits to lifespan.  It is on the other hand exactly the sort of distribution I would expect if that were the case.

 

 

[Daniel Cooper]

Let's wait and see if NR can break the 120 barrier significantly.

 

 

I'll be quite satisfied if it moves the center of the lifespan distribution much closer to that 120 year limit.  That is within the realm of possibility.  If it does, most of us will live to see the genomic limits modified/erased.

[revenant]

Wanting to read full text ASAP

 

http://science.scien...t/355/6331/1312

[MikeDC]

https://www.ncbi.nlm.../?i=3&from=dbc1

[MikeDC]

https://m.youtube.co...eature=youtu.be

[APBT]

Wanting to read full text ASAP

 

http://science.scien...t/355/6331/1312

FULL TEXT:  A conserved NAD+ binding pocket that regulates protein-protein interactions during aging

Attached Files

•  A conserved NAD+ binding pocket.pdf   928.91KB   10 downloads

[Michael]

Michael,
 
 
If there are no inherent limits to lifespan "designed" by the evolutionary process to almost every organism and the only practical limits to lifespan are due to pathological elements in the environment (e.g. tigers, falling off cliffs, radiation, various toxins, etc) then why don't we have evidence of statistical outliers that manage to avoid these pathological elements and live to significantly greater ages?

 
Because of aging . Aging is a real thing, of course: it's just not dictated by a genetic program. Rather, aging is the result of the Second Law of Thermodynamics and being a system that depends for its function on the integrity of its cellular and molecular structures, and yet takes in and processes energy and engages in biochemical reactions. Evolution plays a role in making different species more or less robust against this basic biophysical fact — not because there is selection pressure driving genes that cause us to age (again, that would be redundant and counter to the mechanism of natural selection), but because there is selection pressure driving genes that allow us to live in the face of ongoing entropic, stochastic damage. But of course, there are also competing selective pressures, which explains why different species have more or less robust maintenance systems, structures that are more and less resilient against local sources of damage, and more or less fine controls on its biochemical reactions, See the papers I linked for more on this, and also Steve Austad's excellent book Why We Age.
 

Wanting to read full text ASAP
 
http://science.scien...t/355/6331/1312

 
Provided courtesy of APBT.

[Daniel Cooper]

If lifespan is not a genetically programmed mechanism, then riddle me this ...... why do we see such a strong correlation between reproductive rate, how quickly and how many offspring an organism produces, and lifespan, at least in higher organisms?

 

Do you know of an example of a higher organism that has both a very long lifespan and a high reproductive rate?  That seems to be a definite trade off that suggests that lifespan is part of the program.  

 

Your argument seems to boil down to "evolution would not produce a result where an organism would have as a part of it's genetic program a limited lifespan".  I think that conclusion is very much in debate. If evolution only operates at the level of the individual I think your assertion would probably be true.  But it appears that evolution operates as many different levels simultaneously ... at the individual level, at the species level, and probably at the macro ecosystem level as well. 

 

Finally, your application of the Second Law of Thermodynamics is completely specious.  Entropy will indeed cause ever increasing disorder in a closed system.  The universe is a closed system (as far as we know) so in fact as we do see increasing disorder as time rolls forward in the universe as a whole.  But you and I are not closed systems.  We take in matter and energy on a continuing basis. Just think of where you started from .... You were once a zygote.  It is certainly true that you are far more complex, far more ordered than you were as a zygote.  The Second Law of Thermodynamics simply does not apply in an open system such as ourselves.  It is in no way a limiting factor in our lifespan.  This is the most common misapplication of the 2nd Law that I see.

 

 

[Nate-2004]

Isn't Steve Austad's book 20 years old? Not that it doesn't have accurate information of that time period but I figure we know a *whole* lot more now, even than we did when De Gray's book came out in 2008.

[mrkosh1]

Here is my view.

 

NAD+ replenishment will likely slow down many aspects of human aging or even reverse it modestly. For certain disease conditions it may even work wonders. This is what all the research is telling us so far. As we grow old NAD+ goes down and causes all sorts of problems. However, when damage is already done, additional NAD+ won't allow the body to fix all of the damage that has accumulated. Our genetic programming as adults doesn't allow for full regeneration of tissues. Even if you boost NAD+ to the max, without the genes of embryogensis active, only a portion of the damage will be reversed. For example, a very high level of NAD+ won't trigger the body to regrow lost limbs or replace damaged skin. For that, we'll need to activate a range of genes that are not turned on by NAD+ replenishment. Also, I'm not sure if the body has any means to remove certain waste molecules such as glucosepane. To reverse aging all together, we'll need a range of therapies. But I think of what's available right now NR is probably the top supplement someone can take for overall aging.