Coenzyme Provides Another Clue To Ageing and Cancer
Introduction
One of the theories of ageing suggests that it occurs as a result of a combination of accumulated damage to DNA and a declining ability of our cells' DNA repair mechanisms.
Both these processes act synergistically to impair the functioning of our cells and may also increase the risk of certain types of disease.
A new study in Science [1] suggests a potential mechanism which may be responsible for the reduced ability to repair DNA as people age.
Previous research has found that levels of something called NAD+ (oxidised nicotinamide adenine dinucleotide) decline with age and that this seems to result in an impairment of DNA repair mechanisms.
NAD is a type of compound called a co-enzyme - it basically assists certain enzymes and proteins in their reactions.
These compounds are often derived from vitamins or are vitamins themselves. NAD is slightly more complex than this but that is beyond the scope of this article.
What the Study Found
The first part of the study tested the chemical interactions of NAD+ in human embryonic kidney cells and also human primary fibroblasts (another cell type):
NAD+ appears to bind to and inhibit the activity of a protein called DBC1 (the name stands for "Deleted in Breast Cancer 1").
DBC1 is an inhibitor of an enzyme called PARP1 (poly-adenosine diphosphate ribose) which plays an important role in repairing DNA.
As cells age the levels of NAD+ decline, so there is less of it to bind to and inhibit DBC1. This means that more of the DBC1 is free to impair the activity of PARP1.
The result is less PARP1 activity and therefore a reduced ability of the cell to repair DNA using this pathway.
The second part of the study tested the ability of supplementing NAD+ using a precursor called NMN (nicotinamide mononucleotide) on small samples of young vs old mice.
The old mice had lower levels of PARP1 activity and seemed to be more susceptible (as expected) to DNA damage.
Supplementation with NMN seemed to restore PARP1 activity in the old mice.
It also seemed to reduce the damage to old mice from exposure to gamma radiation even when given after the exposure.
Why does this matter?
Supplementation of NAD+ (or more likely a precursor) might allow a reduction in the accumulation of DNA damage as a result of ageing.
It might also suggest mechanisms by which abnormalities of DBC1 and other components in this pathway may lead to disease.
Supplementation of NAD+ (e.g. using NMN) could help to slow down ageing, reduce the development of certain types of diseases and also reduce damage from exposure to toxic compounds (e.g. cancer chemotherapy) or radiation.
It also suggests other sites of activity which could be explored, for example drugs which block DBC1, or alternatively increase levels or activity of PARP1 (but note the caveats below).
What this study doesn't tell us
This study does not tell us why NAD+ declines with age - that is still not clear.
It also does not tell us for sure whether these effects translate to living human subjects.
The first part of the research was carried out on human kidney cells and the second part on mice with tiny samples (e.g. 3).
So whilst the results are promising they definitely need more exploration.
For some time I have been fascinated by the interplay between ageing and cancer.
One of my personal opinions is that many of the restrictions that contribute to ageing exist in order to reduce the risk of developing cancer.
It seems that evolution has created a very intricate balance between these processes and disturbances to them can create unforeseen consequences.
At first glance it may appear that inhibiting DBC1 is a good thing but remember where it gets it's name from.
It is called "Deleted in Breast Cancer" because in certain types of breast cancer it is missing.
Now this might sound like a good thing given what this study tells us from the point of view DNA repair.
Things are rarely that simple or straightforward though.
As is often the case with biology DBC1 has other effects too. It seems to have an important role to play in something called apoptosis [2].
Apoptosis is "programmed cell death" - and impairment of this mechanism is associated with increased cancer risk.
Further damaged cells which are unable to die in this way, may not just cause cancer, they may also promote other forms of disease and hence ageing [3].
So something which may have positive consequences on the one hand may actually result in other negative consequences.
They may even result in life threatening illnesses like breast cancer.
I suppose the question is, does increasing activity of PARP1 by increasing levels of NAD+ have some similar negative consequences?
The only way to know would be further research.
Conclusion
This study suggests that NAD+ decline as a result of ageing impairs one particular pathway of DNA repair.
It also suggests that supplementation (using NMN) may provide a means of restoring this function at least in isolated cells and mice.
As always we must use caution to extrapolate these results to actual living humans.
It is also unclear if there are any potential negative consequences that might result from supplementation.
As always more research is needed to explore these issues.
N.B. - I have tried to go with a more simplified approach with this post - let me know what you think - is it too much or not simple enough?
Thank you for reading
References
Li, Jun, Michael S. Bonkowski, Sébastien Moniot, Dapeng Zhang, Basil P. Hubbard, Alvin J. Y. Ling, Luis A. Rajman, et al. 2017. “A Conserved NAD(+) Binding Pocket That Regulates Protein-Protein Interactions during Aging.” Science 355 (6331): 1312–17.
Kim, Ja-Eun, Junjie Chen, and Zhenkun Lou. 2008. “DBC1 Is a Negative Regulator of SIRT1.” Nature 451 (7178): 583–86.
Baar, Marjolein P., Renata M. C. Brandt, Diana A. Putavet, Julian D. D. Klein, Kasper W. J. Derks, Benjamin R. M. Bourgeois, Sarah Stryeck, et al. 2017. “Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.” Cell 169 (1): 132–47.e16.
All uncredited images are taken from my personal Thinkstock Photography account. More information can be provided on request.
I think that the main research and discoveries are yet to come. But there will be many other questions.
Humanity is already progressing in quantity. And what if you stop aging?
And will this be all for everyone?
Aging is a wise decision of nature or a mistake?
We still have to find out.
Interesting article, thank you.
Everyone wants to live long, but, unfortunately, healthy eating has become a fantasy...
Yes there are certainly ethical issues as it progresses!
At least some studies point into that direction: in my article "Human immortality?" I wrote:
"Amazingly the concept to die and give ones genes to the next generation most of the time seems to be superior in evolution compared to the concept of immortality. The reason for that is that it allows to adapt more easily to a changing environment according to the motto "we age because the world changes" - also computer simulations seem to confirm that."9, 10
9: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0024328
10: http://www.spiegel.de/wissenschaft/mensch/neue-computersimulation-altern-macht-die-menschheit-staerker-a-795152.html
The more cycles of birth-death, the sooner the development takes place.
I respect your point of view to imagine and believe into reincarnation. Actually it is a very nice association. But as long as there are no real facts hinting in this direction, in my eyes it is kind of wishful thinking ... I cannot exclude the possibility completely, but according to what I know I consider it as not to be very likely ... Maybe we will know it after our physical death. :-)
There are interesting works: Osho Rajnishi, Carlos Castaneda, Raymond Moody and others.
This is certainly an amateur.
But the fact that we are not only a physical body but something more is a fact.
Plus consciousness and subconsciousness.
But we do not control our physical processes consciously.
Kind of like a driver in a car.
Do not stop at one point of view - be in constant search.
:-)
Are you also open to review your points of view? :)
Yes, I also try to make sure of personal experience. But you can come to some things logically. Look carefully at the history of mankind. Everything is based on the physical which is reduced to zero at the end of life.
In addition, all people are born like the same. But in terms of development they are different. And if we take ourselves then we feel ourselves eternally living. Despite the fact that we were born once and one day we die.
Take the physics. Scientists came to the need to recognize the existence of dark matter. Although they can not prove this physically.
I understand it. But I all the same believe that there is physical and there is spiritual. Physical clothing for spiritual fulfillment. And I tend to the point of view that the reincarnation of the spirit works. And the physical body is just a biocost.
In every part of the universe is the manifestation of a great mind and harmony. The physical is not an end in itself but a step in the chain of development.
People are not ready for spiritual immortality. But when they are ready spiritually, then they will not need it. Paradox. :)
Sorry for the comment. Maybe this is not entirely on the topic of the article. But this issue is being shakily affected.
A supplement company called Elysium has put NAD+ in their product to help reduce the affects of aging. Like you said we do not know if these translate to humans but they think it does and made it for people to be able to take. Another source are broccoli sprouts. Why pay for something if you can get it for free naturally? Great post!
Thanks. I will check those out. I love brussel sprouts - I'm wondering if the broccoli ones taste similar. Will need to see if my local farmer's market has them.
I also love brussel sprouts. Honestly I haven't gotten around to eating broccoli sprouts yet. I hear growing them is fairly easy and a lot cheaper. I first heard about this from foundmyfitness on youtube. You can grow them in a mason jar at home in less than a week.
Cool I will check the YT channel out too. Thank you!
Myself and @opheliafu were looking at this a few days ago and everywhere that sells high dosage is sold out. Also the price is pretty expensive. Could be worth a try for a month. Do you have access or can you prescribe it :D
Lol I was thinking that myself. It is not in the BNF for prescribing ! If you take it as a supplement one of the big issues is that there is no way of being certain that it actually contains what it is supposed to even if it is expensive. If this research pans out and there are no side effects I suspect it won't be long until we get pharmaceutical grade NMN or something similar. It shouldn't be too expensive either (at least not to produce).
You post so much good stuff, obv. we all miss some..... have you done a post on the importance and general lack of Mg (magnesium for readers) in most peoples' lives/diets?
That would be a killer post if you are taking requests.
You might want to remove the "e" -- in your title also. (aging)
Thanks, not yet. It is not really my area of expertise but I can look into it and see!
Most people are severely Mg deficient as you likely know.
Your stuff gets so many views, I know it would help people who have not heard of this yet and you have super legit research and blogging skills on top.
If you do a post on it, plaster it into a reply somewhere of mine, so I do not miss it.
Full permission LOL
Will do! Depends if I can find an open study on it or something that is included in my subscription service (not all papers are).
I've heard that average Steemer lives longer than the average of general population!
Lol maybe :)
He is probably completely right: Intelligent people have a longer lifespan. :-)
I wish that were true, haha. My body is slowly failing on me year after year. The sad part is I'm only in my 20s.
Lol :)
Did the study test naked mole rats for their levels of NAD+, DBC1, and other proteins? Just wondering because naked mole rats seem to be able to resist aging and cancer.
No it was just mice and human cells but that would be fascinating to see!
We have a program called Carte Blanche every Sunday here and last night's episode covered this topic - it was fascinating! Great article, upvoting and resteeming!
Thank you so much. Is it available online?
Irritatingly I can't find it on their website - they don't seem to be featuring that segment - https://carteblanche.dstv.com/coming-26-march/
I think it was more than likely based on the same research, I think they said the majority was conducted at the Einstein Institute?
This study was a collaboration between a number of Universities but I don't remember seeing mention of the Einstein Institute.
So bizarre that I can't find reference of the segment, I'm going to try and contact them, I'll let you know if I find anything
Thanks.
I have read a few of these before and the conclusion is normally we just have no idea why yet the body repairs or say renew less also I found your idea of ageing to exist in order to reduce the risk of developing cancer interesting as I have not heard or thought of it myself.
Thanks:)
In a study, the researches conducted ‘extensive analyses’ of blood samples for 100 patients across multiple years. They found a ‘fundamental inflammatory mechanism’ kicks in as one ages, but coffee can help stop it which is one reason as to why coffee drinkers tend to outlive those who don’t consume.So Drink coffe and live longer :P
thanks for posting this useful share..
You're welcome!