The Epigenetics Revolution

This deal was considered expensive by many industry observers, and it hasn’t been without its problems. In 2009, a group from rival pharmaceutical company Amgen published a paper. They claimed that resveratrol did not activate Sirt1, and that the original findings represented an artefact caused by technical problems[257]. Shortly afterwards, scientists from Pfizer, another pharmaceutical giant, published very similar findings to Amgen[258].

It’s actually very unusual for large pharmaceutical companies to publish work that simply contradicts another company’s findings. There’s nothing much to be gained by doing so. Pharmaceutical companies are ultimately judged by the drugs they manage to launch successfully, and criticising a competitor in the early stages of a drug discovery programme gives them no commercial advantage. The fact that both Amgen and Pfizer went public with their findings is a demonstration of how controversial the resveratrol story had become.

Does it matter how resveratrol works? Isn’t the most important feature the fact that it has such dramatic effects? If you are trying to develop new drugs to treat human conditions, it unfortunately matters quite a lot. The authorities who license new drugs are much keener on compounds when they know how they work. This is partly because this makes it much easier to monitor for side-effects, as you can develop better theories about what to look out for. But the other issue is that resveratrol itself probably isn’t the ideal compound to use as a drug.

This is often an issue with natural products such as resveratrol, which was isolated from plants. The natural compounds may need to be altered to a greater or lesser extent, so that they circulate well in the body, and don’t have unwanted side effects. For example, artemisinin is a chemical derived from wormwood which can kill malarial parasites. Artemisinin itself isn’t taken up well by the human body so researchers developed compounds that were variants of the chemical structure of the original natural product. These variants kill malarial parasites, but are also much better than artemisinin at getting taken up by our bodies[259].

But if we don’t know exactly how a particular compound is working, it’s very hard to design and test new ones, because we don’t know how to easily check if the new compounds are still affecting the right protein.

GlaxoSmithKline is standing by its sirtuin programmes, but in a worrying development for the company they have stopped a clinical trial of a special formulation of resveratrol in a disease called multiple myeloma, because of problems with kidney toxicity[260].

The progress of sirtuin histone deacetylase activators is of keen interest to all the big players in the pharmaceutical industry. We don’t know yet if these epigenetic modifiers will set the agenda, or sound the death knell, for development of therapies specifically aimed at increasing longevity or combatting old age. So, for now, we’re still stuck with our old routine: lots of vegetables, plenty of exercise and try to avoid harsh overhead lighting – it does nobody any favours.

Chapter 14. Long Live the Queen

All my possessions for a moment of time.

Attributed to Queen Elizabeth I

The effects of nutrition on the health and lifespan of mammals are pretty dramatic. As we saw in the previous chapter, prolonged calorie restriction can extend lifespan by as much as one-third in mice[261]. We also saw in Chapter 6 that our own health and longevity can be affected by the ways our parents and grandparents ate. These are quite startling findings but nature has provided us with a much more dramatic example of the impact of nutrition on lifespan. Imagine, if you can, a dietary regime that means a select few in a species have a lifespan that is twenty times longer than that of most of their companions. Twenty times longer. If that happened in humans, the UK might still be in the reign of Queen Elizabeth I, and would expect to be so for about another 400 years.

Obviously this doesn’t happen in humans, but it does happen in one common organism. It’s a creature that we all meet every spring and summer. We use the results of its labour to make candles and furniture polish, and we have eaten its hard-earned bounty since the very beginning of human history. It’s the honeybee.

The honeybee, Apis mellifera, is a truly extraordinary creature. It is a prime example of a social insect. It lives in colonies that can contain tens of thousands of individuals. The vast majority of these are workers. These are sterile females, which have a range of specialised roles including gathering pollen, building living quarters and looking after the young. There are a small number of males, who do very little except mate, if they are lucky. And there is a queen.