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“