Is there a way to reverse aging? It’s the stuff that legends and myths are made of – the ever-elusive Fountain of Youth. But a paper published a few days ago in the prestigious journal Cell might make reversible aging closer to a reality (but it is still probably a long ways off). Specifically, by understanding how a key part of the aging process happens on a molecular level, the researchers were able to give two-year-old mice (“old” mice) a specific chemical compound and, after just a week, their tissue resembled that of young, six-month-old mice.
So how does this chemical compound work to essentially reverse aging? It has to do with our mitochondria. Most of our body’s cells have many mitochondria in them – the mitochondria are organelles (specialized structures in the cell) that help produce energy for the cell. And as we age, our mitochondria become dysfunctional. (It’s poorly understood why this happens, even though we know that it does happen.) Part of this dysfunction is that the mitochondria have more difficulty correctly communicating with the rest of the cell. The recent Cell paper not only figured out what key players may be causing this communication breakdown, but also how to fix it. This has ground-breaking implications for understanding and treating aging in people.
One of the key players is NAD+ (which is short for nicotinamide adenine dinucleotide). NAD+ is a chemical compound found in all living cells, and for unclear reasons the levels of NAD+ decline as we age. Certain levels of NAD+ are needed to make sure a different important player, SIRT1, can do its job. SIRT1 (also called NAD-dependent deacetylase sirtuin-1) helps make sure that mitochondria communicate well with the rest of the cell by preventing another player from acting. This meddlesome third player is called HIF-1 (short for hypoxia-inducible factor-1). Usually HIF-1 is only activated when there’s a decrease in oxygen (or, interestingly, in some cancers). However, as cells age and the levels of NAD
To see if these messed-up communication pathways could be fixed in aged mice, the researchers did the logical thing – they increased the levels of NAD+ in the old animals. The “old” mice they used were two-year-olds, or the equivalent of 60-year-old humans. After giving the animals an NAD+-inducing chemical compound for just one week, the animals’ tissues resembled those of six-month-old mice, or the equivalent of 20-year-old humans. Clearly it made remarkable changes in the mice. (For those interested, the exact compound the researchers used was nicotinamide monomucleotide [NMN], an intermediate of NAD+.) All that said, the researchers are still investigating whether increasing NAD+ levels this way can actually give mice longer, healthier lives than usual.
As a side note, a link between activated HIF-1 and cancer is also of great interest – investigating this connection further could help us better understand how cancer is related to aging.
So while a Fountain of Youth is unlikely to be on the horizon, this recent publication may help pave the way to anti-aging treatments as the roles of NAD+ and other key players become better understood.
For further reading:
- Teisha J. Rowland’s book Biology Bytes: Digestible Essays on Stem Cells and Modern Medicine
- Ana P. Gomes’s et al. article “Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication During Aging” in the journal Cell
- David Cameron’s article “A New – and Reversible – Cause of Aging”
- ScienceDaily’s article “New – And Reversible – Cause of Aging: Naturally Produced Compound Rewinds Aspects of Age-Related Demise in Mice“
(after reading your piece, before reading the actual Cell article — although I did browse the figures a little):
1. Where do the researchers give the mice the NAD+? subQ? Bloodstream?
2. how does the mouse body know to stop aging at “6 month-old”? Does it have to do with the level of NAD+ given? Did the researchers give the mice specifically the dosage that match that of the 6 month-old mice? If so, why does the body not need extra NAD+ for the damage past aging has caused? How does the body know NOT to further reverse aging process to, say, infancy (mouse version of the Curious Case of Benjamin Button)?
3. If our aging process is being controlled mainly by the physical status of mitochondria in our bodies, it would be very interesting if someone can piece together that part of co-evolution (big bullying Eurobacteria bossing the poor small prokaryotic mitochondria ancestors into producing ATPs, but got a big kicked from behind when the nerdy hardworking mitochondria reverse the pecking order by setting the age limit of the organism…).
4. in your blog, you mentioned that the muscles appeared to be functioning like that of a 6 month-old mice. What about other systems? Reproductive system? Cardiovascular system? Digestive system? Memory? It would be a bit useless to have muscles of a 20 year-old man and rest of the systems to remain those of a 60 year-old person… That would be very very sad…
5. also, I glanced (couldn’t browse and couldn’t enlarge the figures for some reason — probably because I am now OFF UCSB campus…) the figures — all showed blots. I am “assuming” (a very dangerous and probably very stupid thing to do and admit…) they are measuring the enzyme expression / activities in muscles. Why did they not measure the physical activities (running stamina / breeding fertility / memory test in form of maze running)? For some reason, I thought that was now the standard thing to do with mice (from my brief rotation at Mahan’s lab…).
Thanks for your interesting questions! Here are my responses:
1. The mice were given a precursor of NAD+ called nicotinamide mononucleotide (NMN). They don’t specify how it is adminstered — just that they had “treatment” for one week. They reference a Yoshino et al., 2011 paper, so there may be more details in it.
2. I’m not sure they’ve quantified the effects of the NAD+ to know how concentration/dosage correlates with age reversal. I think more studies will need to be done to figure that out (and figure out why it reverts to the age that it does). I think this is really the first study that’s demonstrated this. Those are definitely interesting questions that I hope will be investigated in the future.
3. I agree — it would be interesting to look into the co-evolution more. I haven’t done a literature search, but I wonder if there’s already some information on that out there.
4. In the paper, they looked at muscle atrophy, inflammation, insulin signaling, glucose uptake, and other muscle functions. While seeing improvement/anti-aging in these areas, they did not see it in muscle strength, however — they propose that more than 1 week might be needed for this. It’d definitely be interesting to see how treatments over a week long would have different results.
5. I am guessing that this group was more interested in quantifying biochemical changes, probably because this is an early paper on this topic — I would imagine that follow-up studies would definitely look into physiological changes.
I found a company selling a supplement containing NAD (www.zaoreset.com) and am thinking of trying it. Has anyone any else tried this product yet?
Thanks for your comment and link, Melissa. I think that more research definitely needs to be done before this could be recommended as a supplement for humans — this study was only done in mice, and the results were limited (to this single published study). As when considering taking any health supplement, it is important to first discuss it with your doctor.