The quest for immortality

Just a glance at a fashion magazine is enough to show that the predominant image of the human condition is that of eternal beauty. But perhaps what people are really after is something more radical: immortality.

Many writers have looked at the subject, such as Edgar Allen Poe (The Facts in the Case of M. Valdemar), Oscar Wilde (The Picture of Dorian Gray) and John Wyndham (Trouble with Lichen). More recently, Jerome Bixby wrote the film The Man from Earth on this subject.

Science has also worked on the concept. Ageing is apparently to some degree written into the human genome, just as for all species, because programmed cell death is essential in modelling the body during embryology and in keeping it in good shape during life. Unfortunately, after the body reaches physical perfection, it appears to be condemned to a downwards slope along which gravity progressively moulds its sagging forms. Is ageing actually written into the human genome? If so, what advantage can ageing bring to the species?

Perhaps the answer to this lies in the story of evolution. Man’s ascent to his position at the apex of life, starting from a unicellular organism floating in the primordial broth, necessarily required millions of successive generations. The inheritance of beneficial characteristics deriving from random genetic mutations requires reproduction, and the survival of the next generation is simpler when the previous occupants have made room by unobtrusively departing from life.

Mutations occur all the time during cell divisions, and some of these have an effect on cell mortality. Why, one asks, have there been no mutations in the other direction, from mortality to immortality? If the course of evolution has been so prolific as to generate so many strange and hyperspecialized creatures such as koalas, giraffes, rhinos and hippos, surely it could be conceivable that at one stage in history, a man – or an animal – was born with a genetic malformation that condemned him, her or it to immortality?

Of course, if ever a mutation gave rise to a man with the genetic apparatus enabling immortality, he could have been killed in his prime on the battlefield of the Somme, or – if he was a fly – mercilessly exterminated by a dexterous blow from a flyswat. We would never know, and the unfortunate individual would not have succeeded in passing his momentous genetic heritage on to the next generation.

Surely, bodily ageing serves no real purpose? A useless and ultimately detrimental inheritance, like the appendix? We know that nearly all human cells are constantly replenished by means of their own internally-programmed cycles of death and renewal. Our skin is constantly generated from below, while the top layer of dead cells is eliminated by daily wear and tear, or by cosmetic peels and scrubs. But, while admitting the necessity for short-cycle death and renewal of body cells, what need is there for those progressive, long term, irreversible changes that cause the skin to become less elastic and more wrinkled?

Over the last few years, some answers have been provided to these questions. Scientific research has recently made radical discoveries regarding the mechanisms of cell ageing. A fundamental role in the process is played by a section of DNA at the end of a chromosome, called a telomere, which protects the DNA sequence during cell division. The enzymes responsible for chromosome duplication cannot duplicate the entire length of DNA, and at every division, a section of DNA at the end of the chromosome is lost. Telomeres are like sacrificial sections which can get chopped off without compromising the function of the new cell, and so the number of telomeres at the end of each chromosome determine how many times a cell can divide before it becomes unviable. Another enzyme, telomerase reverse transcriptase, determines the regeneration of telomeres, therefore increasing the number of cell divisions possible.

Telomere generation is programmed during embryology and in certain parts of the body (such as the immune system) where rapid cell division is essential. This research – dating to only the last few years – caused considerable excitement in the field, because it seemed to suggest that the ageing process could be controlled or modified by telomerase. But there is a flip side to all this. The unrestricted cell division made possible by telomerase is also the cause of cancer, when a rogue cell proliferates out of control.
Some studies on human populations show that certain inherited characteristics related to telomerase increase lifespan. A study on Ashkenazi Jews published in 2009 shows that the longest-lived individuals inherit a hyper-active version of telomerase that reconstructs the telomeres at the end of chromosomes.
Another research project screened a number of traditional Chinese medicine plant extracts, and found that a natural substance named cycloastragenol is capable of enhancing telomerase activity in the human immune system. This could be used in the treatment of HIV and age-related infections by enhancing the immune system, but there is no doubt that there are hopes that this sort of substance could have an effect on the process of cellular ageing at a fundamental, age-enhancing level. The name of the pharmaceutical company that financed the research, Geron, shows exactly where their real interest lies.

While telomeres provide an inbuilt biological clock that controls development and prevents cancerous cell proliferation, cells are also subject to external influence. Another cause of cell ageing can be identified in the oxidants that are an inescapable consequence of cell metabolism. DNA damage means that eventually the cell is incapable of synthesizing the proteins that it needs to exist and perform its functions, causing its progressive deterioration and death.

This source of damage is relatively unimportant for simple organisms such as bacteria, which divide constantly in favourable conditions, remaining forever young. But in complex organisms, the programmed number of cell divisions can be relatively small – a few dozen divisions – or even nil, as in the case of brain and nerve cells. We receive our ration of neurons during embryological development, and from then on, no cell division is possible. Our nerve cells are the only ones we’re going to get, so we’d better look after them…

Research seems to suggest that the best way of reducing oxidant damage to DNA is to limit cell metabolism to what is functionally necessary. This means a low-calorie regime, or at least a food intake that does not condemn cells to working overtime.

Perhaps one day, further revelations will be provided by studies on small and primitive organisms and their interactions. Algae and lichen are organisms that spend all their time synthesizing complex molecules that they don’t seem to need at all, and simply secrete them. While a rock is incapable of doing anything with them, trees may well benefit from the substances produced by the mossy green covering on their bark, and in some cases, these chemicals seem to be capable of modifying the identity of tree cells, turning their biochemical clock back and giving them functions of youthful reproduction, stimulating growth in order to combat pathogens.

Whether or not other useful substances analogous to cycloastragenol may emerge in this field, at present we can only observe man in his incessant struggle to stave off the inevitable. The age of youth has progressively extended, and women are bearing children later and later in life. Old people are becoming more active, energetic and assertive. In Italy, there are moves to pass a law for equality in pensions, so that women will have to work until they are 65, as for men. And if an immortality drug will ever be discovered, there would doubtless be further taxation reform. The Inland Revenue would never forego the possibility of infinite income tax!