Aubrey de Grey wants to wish you a happy 200th birthday...

Tell us about the Methuselah Foundation. Is it doing well?

We’re doing very well on the donation side of things. We’re getting more and more people interested in giving us non-trivial sums of money – and we’re going to be spending almost three times as much on research this year as we did last year. As well, we’re hoping to continue this rate of growth over the next several years – which we’ll need in order to get the work done.

When you say, ‘getting the work done’ you’re referring of course to your SENS plan (Strategies for Engineered Negligible Senescence). You’ve been known to say that the first person to benefit from SENS may live to be a thousand years old – and that this person could very well already be alive today.

As well, you’ve commented that an entire working solution for human longevity doesn’t need to be achieved all at once – but rather a person needs only to stay alive long enough to be able to benefit from the next big breakthrough - then the one after that - and the one after that. You’ve called this “Longevity escape velocity”. It’s a great phrase!

I always try to be quite forthright and say that the technologies we develop within the next 30 years will probably only give us another thirty or so years of extra life. It’s just that that extra thirty years is a hell of a long time for the technology to grow further.

It’s a little bit counter intuitive to people, because I often make an analogy with simple man-made machines and that we need to perform repair and maintenance on them. As in the case of cars, it’s the rare car that gets a level of maintenance which can keep it going for a hundred years. The difference in the case of the human body is that we don’t have a plan for this sort of maintenance. And so we don’t know what to do quite so well, and we have to boot-strap (roughly: to build simple tools which aim to to work towards greater complexity – editor) to that point.even though the machine (the human body) already exists. Once people understand this concept, it does help them to be much more sanguine about the possibility that we might be able to go from the point we are at in this moment – being able to do virtually nothing about aging – to effectively indefinite life spans within a few decades - which otherwise, would just make no sense at all.

Let’s look at some of the elements of SENS in more detail. One of the seven elements is ‘mutant mitochondria’. (Likely many high-school biology students will recall that mitochondria are the components within cells that are important for energy production. Mitochondria have their own DNA, distinct from the nuclear DNA which when damaged (or mutated) causes cancer.) Can you tell us a little bit more about this? Are mitochondria more at risk for mutation?

Much, much more. First of all the actual mutation happens a lot more often – and for a bunch of reasons. The mitochondrial DNA is in the worst possible place, right next to the most mutagenic chemical reaction that the cell does, namely respiration, the chemistry of breathing – combining oxygen with electrons. So that’s a bad thing in the first place. Secondly, it’s not as well protected as nuclear DNA. Nuclear DNA has clever compaction techniques that are there mainly probably for the purpose of just getting so much DNA into a small space – but mitochondrial DNA is not compacted in the same way, so it is much more exposed to damage. It has some compaction – but not to the same level of sophistication [as nuclear DNA].

Further, there are some types of damage to DNA for which repairing enzymes do not exist in mitochondrial DNA – but do in the nuclear DNA.

You would think that since we had so many copies of mitochondrial DNA within a cell that it would not be a problem if some of them become mutated – the rest of them would be breathing away quite happily and the cell is going to be fine. So the question is, what’s the problem? Some of them may get mutated and so what?

When it was first suggested back in 1972 that mitochondrial DNA might actually REALLY matter in aging it was only a couple of years before Alex Comfort, (author of ‘The Joy of Sex’) said, well hang on, this sounds incorrect because we know that in cells mitochondria are created and destroyed all the time. And therefore we should have a steady state level of damage. Sure. Damage is going to happen at some rate, and the damaged mitochondria is going to be got rid of – and so you’ll be ok. And the whole thing was not exactly forgotten – but not largely pursued for an awfully long time after that.

Now, what we know – in fact what we’ve now known for at least 20 years – is that the opposite happens. What happens is that in non-dividing cells, some mutations as I just described may happen – but in others, the opposite happens. In other words, when a mutation happens in a mitochondrial genome it somehow has a selective (Darwinistic) advantage, so that rather than being destroyed it is amplified preferentially by replication. And there are various theories for the mechanisms explaining why this happens and how this happens.

My first paper in gerontology back in 1997 states that there isn’t necessarily a ‘replicative advantage’ for mutant mitochondria – but rather that they get broken down less easily, or more rarely – they stay out of trouble basically. So that they have a better chance to be replicated more often – even though there isn’t any bias in the replication system.