In my last blog entry, I talked about why aging made good biological sense. It doesn’t seem quite so attractive to the individual. We would like to live longer and not age.

One contributory factor is that we lead unhealthy lifestyles. We are sedentary and we eat too much salt, fat and sugar. Again, this is the result of the conditions that we lived in before we developed a civilisation. Sugar and fat are good energy sources. They were in short supply when we were plains hunter gatherers. If you found some fat or sugar, you ate it in order to improve your chances of making it to the next mealtime. They were not any better for you then than they are now but thy were not something that individuals encountered often enough for it to be a major problem. This is especially true when you consider how short the lifespan of the hunter gathers was – 30 years was a good age. 50 was ancient. A disease that might kill you at 60 was no threat at all. As for salt, it was good for protection against sun since we lose salt when we sweat. That was handy when we lived under the baking African sun but less so when we live in air-conditioned homes.

Interesting, the life expectancy of a male newborn in 1900s America was 49 years. Maybe we are closer to the hunter gatherers than we like to think. In evolutionary terms, they are the same species. Give one a shave and a sharp suit and you would pass him on a street without a second glance.

We also ingest all manner of toxins for their psychotropic effects. We are not alone in this as some other mammals will eat spoiled fruit for the alcohol.

So, as we get older, we tend to gain fat that we don’t need and fur up our arteries with fatty deposits. We are fighting back against this with gyms and drugs called Statins that reduce cholesterol but prevention is better than cure – and I speak as someone who eats too much fat and doesn’t spend enough time in the gym.

Not all species show aging. The common factor seems to be that creatures that never stop growing (such as lobsters) do not show aging and don’t generally die of old age unlike creatures that reach a final growth such as humans.

So, why do we stop growing? Well, there is a regulatory mechanism. Our DNA has tags on the end, called Telomeres. When a cell divides, so does the DNA. I am sure that you will have seen the ball and stick DNA models. In division, one side of the strand goes to each of the cells. The other half of the DNA is then reconstructed so that each cell gets a full strand of DNA – and this is a pretty complex thing with all manner of clever error checking. Now, telomeres are on the end of DNA and DNA division knocks off one of a chain of telomeres. If this can’t happen then the replication fails and the cells die. This limits the number of divisions. The length of the telomere chain is a key factor in cell aging. Old cells have short chains. Young cells have long chains.

So, those pesky telomeres deserve the blame? Can something be done? Well, no, they don’t deserve any blame and yes, something can be done. Unlimited cell division is not a good thing. We need and have mechanisms for regulating this. When it fails, you get uncontrolled replication and that is called cancer. They are cells where something has gone very wrong with the growth regulation. So, to the question of whether anything can be done about the shortening of telomere chains. Something is done – we have a repair mechanism that uses an enzyme called Telomerase which tacks new telomeres on the end of the chain. Some forms of cancer are associated with cells producing their own telomerase.

Could we use telomerase to rejuvenate cells without causing cancer? The answer is yes and no. We can fix up the telomere chains and that will help a lot. However, DNA does get damaged, both in the normal life of the cell and in cell division. Ionising radiation and free radicals all damage DNA. We have mechanisms to detect damaged DNA and even to repair it but they all rely on the mechanism of detection and repair working properly. However, we know that the DNA is damaged in cases where repair is necessary and accordingly, the cell is in an abnormal state. The detection and repair mechanisms may fail and let errors through. How dangerous these errors are will vary a great deal. Some DNA appears to be redundant and errors here probably don’t matter at all. An error to the replication control mechanisms could be fatal not just to the cell but to the organism. This is a place where we must tread very softly indeed. Let us assume that the chance of a dangerous error was 1 in 10 million. 10 million cell divisions really isn’t that long in biological terms.

There are also other factors – not all cells reproduce but they still age. That is because the cells have complex mechanisms that rely on complex chemicals song as lipids. They get damaged just as much as the DNA. When the cell is damaged, it works less well, If it is damaged enough then it dies.

So, what would we need to do at a cellular level to reduce aging? There are a few things that are possible with current technology and a few more which may be possible relatively soon:

- reduce the amount of free radicals. This is actually not that hard to do. Anti-oxidants are good at mopping up free radicals and can be absorbed by humans without trouble. Beta-carotene is just such a compound and it is found in fresh vegetables, especially carrots. So, eat up your greens everyone.

- avoid ionising radiation. Alpha particles are not that bad because they don’t penetrate far in to the body. Beta radiation such as that given out by a conventional television and monitors is a bit worse but manufacturers are increasing keeping radiation levels low. Gamma radiation will go where it wants and there is not much that you can do about it.

- Maybe we can use telomerase to extend cell life and therefore life of the individual

- Maybe we can use Nanotechnology to ungunk blocked arteries and repair damaged structures. If you are unfamiliar with the idea of nanotechnology, it is the production of tiny structures and machines with molecular parts. At present, we only have some very simple building blocks such as a ball (Buckminsterfullerene), tubes (carbon nanotubes) and a design for a toothed gear wheel. It is safe to say that it will be a while before this technology will blossom but it shows great promise.

- Recombinant DNA. It is just becoming possible to patch up DNA using a virus to replace a damaged section of human DNA with a fixed segment. Again, this technology is in it infancy but it is possible that it could be used to repair errors in DNA , bit by bit and so reduce aging.

A child born today can reasonably expect to see his or her 80th birthday.
Maybe their grandchildren will see their 200th.

Next: Something completely different.

Aging - why and how

Much of what I am going to say here goes against Christian doctrine and Feminist ideals. For those who believe that Genesis is the literal truth, I would suggest that you probably don’t want to read this. For the feminists, I sympathise. What I will describe here is about how we are made. We can change how we think of each other and how we act but we can’t change our genes or our past.

People get older. We are all familiar with that and the outward signs. Skin becomes less elastic and wrinkles. Hair loses colour. In men, there is hair loss to a greater or less degree. Women do not experience significant hair loss as it is an effect of male hormones. Women undergo the menopause and there are attendant changes such as osteoporosis. These are macro level changes. However, we have to consider what the human body actually is. We are a collection of cells that cooperate, a complex organism composed of simpler but still complex organisms. To really understand aging, we have to consider how aging affects the cells.
Let us consider why we age. We age because we do not repair ourselves as fast as we are damaged by our environment. This is not terribly obvious at a macro level although you will often hear comments about how the young heal faster. If you are no longer in the first flush of youth (and I am surely in this camp) then this might seem an unfortunate feature of the human body. However, it exists for reasons that make good sense from an evolutionary perspective.

The purpose of an individual from a species perspective is to make more individuals. From our own personal perspective, we might regard our purpose as to play a perfect flute solo or make a million dollars or write the last great novel. From a biological perspective, our purpose is to breed. Moreover, we have evolved to do tolerably well when resources are not so plentiful. We are relatively cheap to build. We could have evolved with better repair systems but that isn’t an evolutionary advantage since each individual would require more resources. Picture this:

Subspecies A (repairers) have good repair mechanisms and can live indefinitely barring predation and accident. For a given level of resources, they can produce 2.1 offspring for each couple. They begin to reproduce at age 30 since they will mature more slowly.

Subspecies B (breeders) have poor repair mechanisms and can live for up to 30 years barring predation and accident. For a given level of resources, they can produce 3.0 offspring for each couple. They begin to reproduce at the age of 14 since they will mature more quickly.

After 14 years, generation 2 of Breeders is on its way. By year 28, the second generation is working on a third. At year 30, the first generation of Breeders is on its way and the first generation of Breeders is dying off. Allowing some time for gestation, that gives us 6 of Breeders (2 died) and 4 of Repairers (none died). Clearly, if unchecked, Breeders will do best.

What happens if we allow for predation and accident? Let us assume that deaths among the young can be replaced because this is what happens in nature. Well, this tilts the balance further in terms of Breeders. Because each individual is “lower cost”, loss of an individual has a less effect. Loss of individuals who have already reproduced hardly has any effect because they would be dying soon anyway and will produce no more offspring. Because the individuals age, it will be mostly the very young and the older members who are caught by predators or freeze in the winter – the young are quickly replaced by Breeders. Repairers will not lose seniors preferentially because of their superior repair mechanisms but they will still lose the very young and they cost more to replace due to the higher resource needs of a fully self repairing mechanism.

So, in both those cases, the cheaper but short lived species wins. What happens if we give both groups a hard time and reduce resources? Repairers can only produce 1.5 individuals per generation and Breeders can only produce 2.5 individuals per generation. Both can still increase but let us factor in accident and predation. Let us assume that .5 individuals per generation are killed in 20 years. This will mean that many of Breeders will die before reproducing and the population will struggle to remain at its previous level. Since Repairers do not reproduce until much later, many more of them will die before reproduction. Again, Breeders do better. This model is conservative since many species can produce more than 4 individuals per generation.

So, although it doesn’t suit the individual to age and die, it does suit the species. If we look at populations of species, we se that this pattern is followed everywhere. Insects are cheap, short lived and there are many billions of them. Rats are a little more expensive and live a bit longer and there are billions of them. Elephants are expensive, long lived and there aren’t very many of them.

Ah, but hang on! There are billions of humans now and we are not that much cheaper than elephants. Well, yes, that is true. We cheated. By developing intelligence, we have changed to numbers in our favour. By cooperation, we have almost eliminated predation. We build shelters against the sun. We wear clothes against the cold. We plant crops so that there is food in the lean times. In evolutionary terms, this happened an eyeblink ago and we still have the same design at cellular level that we always did have. We are slow breeders, not repairers.

Actually, there is an interesting little wrinkle with humans. Human females live longer than males, well past reproductive age. This sounds like a glitch but it isn’t. Evolution works on groups as well. Intelligence and experience can help a group survive. Groups where there were still older females around did better and so passed on their genes. Why older females rather than older males? Well, because males were more exposed to danger and so were less likely to grow old. In species terms, this makes sense as well. Human gestation is 9 months. Single births are the most common case. One woman can bear one child at a time but a man can be the father of multiple children by different mothers at any one time. If anyone is expendable, it is the men, not the women. Of course, it is handy if the man is around to do his share of looking after junior but in a cooperative society, the offspring will probably survive anyway. So, men were preferentially exposed to danger and older men were more likely to get trampled/gored/eaten than the younger men.

So, that is where we are. In the next entry, let us continue and have a close look at cellular biology.

First word

Welcome to TangledThreads, the blog of an unremarkable man.

If there is an established protocol for how to start a blog then it is not one that I know. Instead, I shall explain why I am doing this.

I have a bad habit that my friends are kind enough to tolerate. That bad habits stems from who I am. I find a great many thing interesting. I like to share ideas. Unfortunately, in my case, this means that I tend to respond to questions which lectures. One of my friends has extended this tolerance to a degree where he feels that my rambling discourses should be accessible to other people in the form of a blog. Indeed, he has gone out of his way to ensure that I do this. Accordingly, I have created this blog.

Perhaps I should say a little about who I am as an introduction - doubtless I will fill in a profile but some context may be helpful. I am 40 years old, male and currently live alone though I am part of a long established long distance relationship. I live in rural Berkshire in the south east of England. I have a scatter gun approach to interests and switch between them in an apparently random fashion. Among things that I might talk about are:

- Science
- Computers
- Poetry
- Fiction
- Music, especially Blues and Filk
- History, especially British history, especially the history of Roman Britain
- almost anything else that takes my fancy outside of the core areas.

I am not a known expert on any of these subjects with the exception of a particular area of computing - I work for a large US IT company. I will leave it to your judgment as to how well versed in the other subject I am. All that I can promise is that discourses will be varied. I can not promise that they will be interesting because I have no idea what your interests are.

I don't propose to discuss my personal life very much because it is likely to be dull to anyone who doesn't know me and uncomfortable for those that do.

If you have any questions and feel that I might have an answer then please feel free to post them as replies. I can't undertake research campaigns for you but I will answer if I have any knowledge of the subject or any views.

I thank you for your interest on the safe assumption that you will not have read my thanks if you didn't read the rest.

Blues