Human Ageing Genomic Resources announced last week their on-line database of animal studies that evaluated drugs and supplements for extended lifespan. HAGR is a project of the University of Liverpool, spearheaded by João Pedro de Magalhaes, who has been an activist-scientist in aging research since his days as a grad student at Harvard.
The database is a great resource for researchers, and helps assure that we have no excuse for overlooking a substance or a perspective or a particular result. Maintaining and updating it will continue to be an important and demanding project.
The full database covers 1316 studies, and I will review here just those on mice and rats. My reason is that life extension in simpler animals turns out to be too easy. There is much we can learn about universal biochemistry from studies in worms and flies, but most of the successes there fail when the (longer and costlier) studies are done in mammals.
Here is a spreadsheet extracting just the 93 studies on mice and rats. You can view it online, and if you download it or copy it into your own GoogleDrive account, you can sort and edit and re-arrange it at will.
Rapamycin: Has the most studies and the best data. Clearly works, but has side effects and it is not yet clear if it is appropriate for general use. Make your own decision. [read more]
Metformin: We have extensive experience with humans, and clear indications that it lowers cancer rates and ACM*, but there are dangers and side-effects. [read more]
Melatonin: Good evidence for modest life extension in rodents. For some people, it’s also a good night’s sleep; for others it can lead to grogginess or depression.
Aspirin: The best evidence for lower cancer and ACM* is in humans. Most people can tolerate a daily mini-aspirin without stomach complications.
Epithalamin (and other short peptides): This is work by Anisimov in St Petersburg, and it is so promising that I can’t understand why it isn’t being replicated all over the world. [read more]
Deprenyl: Old studies, but they show consistent, if modest life extension. It affects CNS in ways that you might feel, might like or might not. [read more]
Acarbose: A diabetes drug that blocks the digestion of carbohydrates. Side effects and toxicity make it less promising than metformin as a general recommendation. [drug info]
C60 Fullerene: Just one study in 6 rats, with spectacular results. Replication has failed [private communication from Anton Kulaga]. Nevertheless, there are thousands of people experimenting on themselves. [read more]
Curcumin: There are major questions about absorption and dosage, but no question that anti-inflammatories are a good general strategy, and curcumin is a good anti-inflammatory. [read more]
Green tea: Small but consistent life extension from polyphenols extracted from tea. From a number of high-profile experimentalists, 2013.
Resveratrol: Works great in simpler animals, including some vertebrates, but in mammals life extension has been limited to overweight mice on a high-fat diet. [read more]
The New Part
BHT: This is an anti-oxidant and chelating agent, which means that it is attracted to metal ions, it pulls them out of circulation and takes them out of commission. This sounds good when it’s removing mercury or lead, but less good when it’s removing iron and dangerous if it’s removing zinc or other essential trace minerals. BHT has long been used as a food packaging additive to preserve freshness, and it is still avoided by natural foods types. This Russian study  found 17% life extension in mice.
Creatine: Used by body-builders, it encourages muscle growth by blocking myostatin. It also increases nerve growth, and slows shrinking of the brain. In one promising mouse study , average lifespan increased 9%.
Icariin: This is an active ingredient in the traditional Chinese herb which in the West is known as Horny Goat Weed. One mouse study, 6% increase in lifespan.
VI-28: Another Chinese herb. Just one study, up to 14% increase.
Royal Jelly: Queen bees are genetically identical to worker bees, yet they live 100 times longer. Is it the royal jelly they are fed? One mouse study  showed a 25% increase in mean lifespan, but no increase in max lifespan.
N-Acetyl Cysteine: Glutathione is an antioxidant associated with mitochondria. Unquestionably, glutathione is a good thing. Too bad we can’t just eat it. The next best thing is to take the precursor, NAC, which seems to lead to increased glutathione throughout the body. This one study  came out of the same prestigious group at Jackson Labs that brought us rapamycin. Mean lifespan increased a stunning 25%. Two reservations: (1) they used enormous dosages, and (2) the mice on high-dose NAC ate less, so they probably benefited from caloric restriction.
Ginkgo biloba: Extract from the stinky fruit of an ancient oriental tree. Traditionally used as a neuroprotective and concentration enhancer, for which it is mildly effective. In 1998, a single study found 17% life extension in rats. Who knew?
The Bottom Line
Clearly there is a great deal of promise here, but there is also much work to be done before we have it sorted out.
- Many treatments have shown promising results in just one study, and that needs confirmation. My top priorities would be epithalamin, NAC, and royal jelly.
- Other treatments inspire enough confidence that we should be optimizing dosage for human use.
- As I have written, the most important work before us now is to see how these different treatments combine. Most combinations won’t work together, but when we find the few that synergize we will have a candidate protocol for major life extension in humans.
If you’re curious, of the substances reviewed here, I personally take metformin, aspirin, creatine and NAC. I season with turmeric a few times a week. I have dabbled with deprenyl and rapamycin.
* All-Cause Mortality