Ageing
Most people do not want to talk about death and human life is held up to be absolutely sacrosanct; any death is a tragedy. There seems to be a taboo about admitting that we will all have to die one day. I think it is quite likely that lots of people think that it is possible we won’t have to. After all, it is remarkable how longevity has increased in the last 50 years. We have made such strides in achieving a long and healthy life for so many people, that we are beginning to think that we might in the end cheat death. That is, that there might be a cure for old age, and that people in the future can live very long lives without showing the signs and symptoms of ageing that I have been talking about for the last few blogs.

Might this be possible?

It should be obvious that all life forms do show signs of age and ultimately die, though some do it at faster rates than others. There are some animals that live a very long time, and we already live longer than most similar size animals, so it is as legitimate a subject as any other for scientists to try to work out what is happening to us, as we get older, and to prolong life.

Almost all the work done to date has been on laboratory animals such as mice and rats, and most of the scientific enquiry going on in this field is in America. Very few European institutions are studying it in detail, and there is a good reason for this – the global market in anti-ageing products is worth probably more than £190bn annually. A lot of money can be made out of old age health in a completely market run economy even if there aren’t any measurable improvements in overall population health. It is true that there is vast scope for snake oil salesmen here. It is also a field in which the safety of any medicines would be paramount. After all, if you were going to take new drugs for long periods of time to prevent ageing, they would have to be absolutely safe. It is a bit like common disorders like irritable bowel syndrome. Some promising drugs, which cure this, have been discovered in the past, but they had side effects. There is no chance of such drugs getting to market, as IBS is not going to cause serious disease. But that does not stop scientists looking.

There are many theories of ageing – apparently at least 300. Most assume that over time our tissues are damaged by something in the environment. For instance we know that free radicals, atoms or molecules with a single unpaired electron which makes them chemically very reactive, can break down intracellular molecules, so that junk accumulates in our cells that can’t easily be broken down and eliminated. So scientists look at how and where that damage happens and how it leads to the organism’s death.

Many theories look at our DNA – the building blocks of life – to see how death happens. For instance, if the DNA in the nucleus of the cells is damaged by oxidation, this causes errors in the copying of the cells when they divide, so that they are not so long lived. But such damage, if it occurs in one DNA strand, can be repaired each time the cell divides by the other complementary strand, if that is undamaged. So the damage is more likely to lead to long-term deterioration in cells which do not divide often. There is good evidence that such long term DNA damage is a cause of the changes seen with the ageing process.
What is not thought to be the cause is chance mutations occurring in our DNA, not specifically due to damage. The reason for this is that mutations in a particular cell which give that cell an advantage in dividing tend to cause cancer rather than normal ageing.

More recently, attention has focussed on the telomeres in DNA. Telomeres are short segments of DNA which cap the ends of every chromosome, acting as ‘buffers’ against wear and tear. They shorten with every cell division, eventually getting too short to protect the chromosome, causing the cell to malfunction and the body to age. In fact this theory has got as far as the experimental stage, as a lady in the USA (who had shorter than usual telomeres) has received gene therapy to reverse the process and lengthen the telomeres in her white cells. It appears that this has been successful in the white cells in her blood, but of course we won’t know for many years whether this has an actual effect on how this lady ages. The therapy is supposed firstly to protect against loss of muscle mass with age, and also to prevent stem cell depletion responsible for many age-related diseases. so we may be able to see if this actually occurs, at least in one person.

It has also been noticed (in rats) that a calorie restricted diet can be effective in prolonging life spans under certain circumstances, due to the diet’s effect on an insulin-like growth factor signalling pathway. This responds to an animal’s nutritional intake, matching growth and reproduction to food availability—and also, it seems, affecting health and longevity. But in my limited experience of the 90 year olds and centenarians I looked after, they all seemed to enjoy their food and none of them gave a history of restricting their food intake deliberately in order to live longer.

Another theory looks at the enzymes in cells responsible for repair mechanisms. Most scientists agree that free radical oxidative damage would be impossible to prevent, so they turn to cellular repair mechanisms to see if these can be boosted. The maximum lifespans of humans, naked mole rat and mouse are respectively, 120, 30 and 3 years, and when the DNA repair mechanisms of the liver of these animals were compared it was found that the longer-lived species, humans and naked mole rats had more effective DNA repair genes, than did mice. In addition, several DNA repair pathways in humans and naked mole-rats were up-regulated compared with mouse suggesting that increased DNA repair facilitates greater longevity. But no-one has succeeded in this yet.

All in all therefore, despite a lot of research, you won’t be surprised to learn that there are no magic bullets to postpone death which are coming on stream any time soon, and some scientists argue that it is impossible to prevent the sort of damage to cells mentioned above that cause ageing. Consider the fact that everything in the world wears out in the end. Until we can stop mechanical machines, which are composed of much simpler molecules, from wearing out, we are not likely to be able to do this in animals. After all we know that cancer is a simple problem – the overgrowth of cells which causes tumours, and spread. These cells need to be killed off, but despite huge amounts of money and decades of research there’s a lot of cancer we still can’t cure. More hopefully, other scientists say there’s no law of physics that says we can’t alter the process of ageing.

But let us assume that effective methods to control ageing do become available: stem cell implants, gene therapy, whatever. How many of us would be prepared to bear the cost in time as well as money? The first guinea pigs would have a life dominated by a never ending round of medical appointments, check-ups, discomforting procedures, and heaven knows what else. Would the extra years be worth much if mostly taken up with the getting of them?
Some people do live to 110 or more now, and if they continue to enjoy life and society is able to look after them, that is fine. But if you ask people in their sixties and seventies how long they want to live, most say they would like to reach their eighties, and some their nineties, so long as they continue to enjoy good health. But there is no great enthusiasm to live until a hundred and more. People are realists. If only a few people get to live longer, inevitably their friends would be dead. Even if still very wealthy it is unlikely they would be allowed to contribute much to society, as the power and influence have passed, rightly so, to the generation below. Unless of course such a person, very successful in life previously, had gained a great deal of power and managed to hold on to it. Robert Mugabe comes to mind.

And for the world at large, whether finding such an elixir of life would be a good thing or not is very debatable. After all, only the richest would be able to afford it for many years. If it ever got to the state when ordinary people would be able to do it, it would contribute to the gross overpopulation of the planet we have already. It would be totally unsustainable, and would contribute to competition of richer people for the resources with which to continue living and the costs there of, hereby causing all the more inequality. I think we should be very careful what we wish for.

References

Best,BP (2009). “Nuclear DNA damage as a direct cause of aging”
Aging (Albany NY). 2015 Dec;7(12):1171-84.
BMJ 2011;343:d4119
April 22, 2016 | Editor Neuroscientist News First gene therapy successful against human aging