Image from flickr user milajake under a Creative Commons CC BY-NC 2.0 Licence
What if I told you that you could take one pill a day and it would make you live longer? It might sound like science fiction, but it’s likely that in the not-too-distant future, this may well be an option. I suppose the qualifier here is that almost everyone would agree that we wouldn’t want to live longer if that just meant extending the end of our life. What I’m talking about is if we could find medicines that actually slow down the overall aging process – so we get more of what aging scientists call “quality-adjusted life years” – or another way of putting it is increase our “healthspan”. The fact is, despite the fact that we don’t actually understand what aging is (if we did, we might find it easier to do something about it), we know of a number of drugs that in a variety of animals, do just that, extend the lifespan of the animal but no-one has yet been able to conclusively show that these work in people.
I should mention that there are potentially other ways that may extend lifespan – caloric restriction has been shown to work in a wide variety of animals – including mammals such as that favourite lab animal, the mouse. There’s an obvious problem with this – I don’t know about you but to me the sound of cutting my daily calories by several hundred sounds pretty objectionable. The other thing that gets mentioned with regard to aging is use nanotechnology to prevent or repair the damage of aging – but in recent years it seems like nanotechnology gets touted as the solution to almost any problem so we’ll see about that one.
Anyway, back to drugs. There are a number of drugs that show potential promise. Resveratrol is a chemical that is found in the skins of grapes, blueberries, raspberries and mulberries. It has been known for a few years to mimic the effects of calorie restriction, extending the lifespan of yeast, C. elegans, Drosophila and Zebrafish. It seems to affect the activity of a group of enzymes called sirtuins. which are known to be involved in the aging process. It has been shown that SIRT1 (that’s sirtuitin 1) is a target of resveratrol and it’s even known which part of the SIRT1 protein resveratrol connects to. But, critically, resveratrol hasn’t been proven to slow aging and repeated studies are leading to doubt that it can reduce blood pressure in humans. This and other effects would help to increase average lifespan without actually slowing aging.
Another drug that has caused some excitement in the field is Rapamycin. This bacterial metabolite was originally identified in a soil sample from Easter Island and showed initial promise as an anti-fungal agent. However development of it as an anti-fungal agent was abandoned when it was realised that it has immunosuppressive effects and inhibits cell growth. An anti-aging effect of rapamycin was initially recognised in Drosophila and has been demonstrated in some vertebrates, including mice (although a team of German scientists have suggested that rapamycin doesn’t actually slow aging in mice, but stops them from dying of cancer – the leading cause of death in these mice). The target pathway of rapamcyin is known and was imaginatively named the “target-of-rapamycin” (TOR) pathway (seriously). The function of the TOR pathway is to promote cell growth when nutrients are abundant and when nutrients are scarce, stop protein synthesis and “recycle” resources (“autophagy”). This pathway is known to contribute to the anti-aging effect of caloric restriction and effectively rapamycin mimics caloric restriction. This all sounds great right? But the problem is twofold – rapamycin is an immunosuppressant (and is medically used as one) and hasn’t actually been shown to have an anti-aging effect in people – and because it is inhibits the immune system, it’s probably not going to be tested for anti-aging effects any time soon. It is possible, however, that another drug could be developed that targets the TOR pathway but doesn’t have such an immunosuppressive effect (and don’t worry – people are looking!).
Probably the most exciting of the known drugs that could potentially have anti-aging effect is metformin. Metformin is primarily used to treat type-2 diabetes, as it has the effect of lowering blood sugar levels and increasing insulin sensitivity. This causes a reduction in risk of various complications of type-2 diabetes, including heart disease. Studies of metformin in mice have shown that it reduced oxidative stress and inflammation and increased both lifespan and healthspan. In a large study of diabetic patients compared to similar non-diabetic people showed that overall diabetic patients on metformin had similar levels of mortality to non-diabetic people, but in those patients over 70 years old, mortality in the diabetic people on metformin was around 15% lower than the non-diabetic group. That’s quite an exciting result, but without further study, we don’t know if it’s real. A group of scientists in the USA are attempting to convince the US drug regulator the FDA to allow them to run an aging trial with metformin – in which case we could get a proper idea of its effectiveness.
So, there have been some headline-grabbing potential anti-aging drugs. Nothing has been shown to work yet, but I think that metformin looks the most promising and it is turning into a very exciting field. And I don’t doubt that in the next few decades, we’ll know of drugs that can slow aging. In any case, don’t rush of to your doctor demanding some anti-aging pills just yet and stick with the things that are known to work – plenty of exercise, maintain a healthy weight with a balanced diet rich in fruit and vegetables. That’s might not be quite what you were hoping for – but it’s the best we have at the moment.