Biology & Philosophy of Growing Old
When to Begin to Limit Your Driving
We've put more effort into helping folks reach old age than into helping them enjoy it.
- Frank A Clark
What are the warning signs when someone should begin to limit driving or stop altogether? You need not experience them all!
If you notice one or more of these warning signs, you may want to have your driving assessed by a professional or attend a driver refresher class. You may also want to consult with your doctor if you are having unusual concentration or memory problems, or other physical symptoms that may be affecting your ability to drive. Don't wait. This is important.
Why do people grow old? Recent research has revealed something of what happens in ageing, and how it happens. But why? That's another story...
The human race has spent millennia celebrating, damning and defying old age. But understanding it, from a scientific standpoint, has long proved elusive. Why does the body alter so dramatically with time? In the past decade, new tools and fresh ideas have started to give researchers a grip on the "what" of ageing - the complex changes that go on within the body's cells over time. They even have some inkling as to the "how" of ageing, the biochemical processes which may trigger these cellular phenomena. But why the body should become more prone to these pressures in the first place is much debated. Ageing is one of nature's almost universal phenomena - virtually all multicellular creatures, if given a chance, will go through the process - but still one of its most mysterious.
A distinct process
Non-scientists tend to think of "ageing" as a continuous, lifelong process, a series of changes from childhood, or indeed conception, onwards. Most biologists have a different view. They see the period of ageing as one distinct from that of early development. First come the minutes, months or years that a body may spend to put its growing house in order by forming cells into organs and systems. Next comes its reproductive phase. Only thereafter, say biologists, does the systematic increase in molecular disorder set in which, with its effects, amounts to ageing.
Those effects are plain to see: slowing down and a growing susceptibility to disease. It is as if the processes that helped to build the body, and keep it in line, turn against it. Joints stiffen as their molecular mesh of collagen tightens, the same process that helped to strengthen them in early life. Most cells have already stopped dividing in the run-up to reproduction. That is a useful check, then, on disruptive disorders like cancer; but it means that, as ageing organs start to break down, and new cells are needed to replace the old, these are not available.
This might seem an odd design flaw to have slipped past natural selection. But then evolution is all about optimising the passage of genes from one generation to the next. That means, for example, that traits which are advantageous in early life are favoured, even though they may cause later harm. To borrow a comparison from Leonard Hayflick, a cell biologist at the University of California, San Francisco (UCSF), the body is rather like one of the Mars fly-by probes, but engineered to reproduce, not reconnoitre. Once the body's mission is accomplished, nature, like NASA, has little interest in what happens next. The reproductive lifespans of members of a given species are probably thus optimised to match the time an individual of that species might expect to survive before being cut down by accident, predation or disease. Physiological resources go into reproduction, not prolonging life thereafter.
Humanity, however, has increasingly mastered such threats, raising its life expectancy to the point that most members of the species live well beyond their reproductive period of life. Our old age, says Dr Hayflick, is an artefact of civilisation.
Senescence then, according to this hypothesis, is not some self-destruct mechanism, encoded by a specific "ageing" gene, which is suddenly switched on at a certain point in an organism's life, in order, say, to keep population levels in check. But genes do play a role in the process. Studies that have been made of elderly identical and fraternal twins, for instance, suggest that roughly 35% of man's longevity is due to genetic factors, the rest being attributable to a wide variety of environmental factors such as diet.
How the genes concerned contribute to the human ageing process is, as yet, unknown. But one of the great leaps forward in ageing research in the past decade has been the discovery in experimental animals of genes that influence their lifespan. Laboratories around the world are now filled with preternaturally youthful, or prematurely old, yeast, worms, fruit flies and mice created through genetic engineering. This tinkering has revealed a number of biochemical pathways which are involved in the ageing process in such animals.
For example, among roundworms (C elegans, as scientists know the creature), those that have had one of their genes called daf-2 tweaked in the laboratory live twice as long as counterparts that have not. They are also friskier in their old age. The gene in question is known to encode a protein involved in a hormonal system which, among other things, helps cells resist "oxidative stress" - the onslaught of some nasty molecules known as "free radicals". Similarly, the lifespan of mice can be lengthened by almost a third through genetic tinkering that blocks their production of a protein called p66shc, and so makes them better able to resist oxidative damage.
Free radicals are produced continuously as cells go about their daily business, and are churned out en masse when cells come under stress. But the body has a suite of powerful enzymes which act as molecular police to keep these radicals in check. When they do get out of control, free radicals can cause the sort of damage characteristic of ageing cells, including broken DNA and misformed proteins.
One of the most persuasive links between oxidative damage and ageing is the injury that free radicals do to telomeres. Telomeres are the bits of DNA that are found at the end of chromosomes. Many cells spend their lives dividing, and with each division their telomeres become a little shorter. Eventually the cells reach their "Hayflick limit", discovered by Dr Hayflick in the 1960s, at which point they stop dividing, go quiet for a while and then die. The telomere, we now know, acts as a sort of molecular clock, allowing a cell to keep track of divisions and hence of its lifespan. But some cells, such as cancerous ones, keep going on and on. They produce an enzyme called telomerase that keeps their telomeres up to scratch as free radicals break them down. So the cells never reach their Hayflick limit.
Calvin Harley and his researchers at Geron, a biotechnology firm at Menlo Park, California, are trying to genetically engineer bits of telomerase into cells that have stopped dividing, to get them to restart the process and reset their clocks. The firm is careful to point out that this is not a wholesale anti-ageing therapy, but rather (it hopes) a new way of tackling degenerative diseases that may afflict both young and old, such as diabetes, in which certain cells have ceased to function. Geron hopes one day to find drugs that might directly stimulate telomerase production in humans.
Meanwhile, millions of people will go on dosing themselves with "anti-oxidants" such as vitamin A, in the hope of keeping age at bay. Largely in vain: compounds like these are absorbed and distributed through the body in such a way that they have little impact on individual cells.
What does appear to work, at least in mice and monkeys, is to reduce their caloric intake by at least a third. This seems to boost their lifespan by up to 50%, and make them less liable to neurological disorders. But how? Work by Mark Mattson and his colleagues at the National Institute on Ageing in Baltimore, Maryland, suggests that cutting back on the calories reduces the production of free radicals. One can hardly set out to starve humans, but the researchers are working on small molecules that might be able to mimic the effect: they are studying rats to see if one promising compound, 2-deoxy-D-glucose, will lengthen the animals' lifespan.
Hope and experience
There is great hope amongst biologists that new science will fulfil the age-old dream of prolonging youth. Cynthia Kenyon, a worm specialist at UCSF, is optimistic that genetic experiments in other organisms can point the way to the underlying determinants of ageing, not just in flying or furry creatures but in humans as well. She is one of a new wave of developmental biologists who have rejuvenated the sluggish field of ageing research. Their new tools and fresh ideas, taken from the worlds of molecular biology and genomics, give them confidence that "ageing is a disease that can be cured, or at least postponed."
Dr Hayflick, today the grand old man of gerontology, is less sanguine. He reckons that the genetic pathways so far revealed in experimental organisms may tell us about processes in early development, whose pleasing side-effect is longer life, but not so much about what happens in the body as it approaches the end of its lifespan. Nor is that insight likely to come quickly, he says, given the way current biomedical research focuses on the symptoms of old age, such as stroke or heart disease, rather than the fundamental processes going on in cells that make them more vulnerable to such mishaps in the first place. Ageing is not a disease to be remedied, says Dr Hayflick, and those who strive to stave it off are disturbing a process as natural as the development of a child. Like any other walk of life, gerontology too has its generation gap.
Source: The Economist 23 December 2000
A Crisis in Scientific Morale
Why does a person even get up in the morning?
- Barbara Kingsolver
by Robert Pollack
Scientists who work in biomedical fields cannot be objective observers of processes that go on in their own bodies. What is the rational solution to this problem?
So long as individual scientists believe, and behave according to the belief, that the essence of success in science is the freedom to discover the right experiment and then to do it according to one's own lights, all the social structures that connect scientists to one another will be based solely on each scientist's latest piece of individual work: a hobbesian world of each against all. Such a world is intrinsically unhappy, and profoundly unbiological as well, in the sense that no scientist's life, or work, can possibly go on indefinitely, as this sort of world demands.
This wilful miscalculation of the trajectory of a life can, paradoxically, lead to sudden demoralization in those scientists who have been around long enough to know better. As they reach an age and situation where "peer review" means being judged by colleagues younger than their children, the absence of social structures that would validate anything about these researchers beyond their latest papers, makes fora reproducibly sad moment of isolation that often leads to bitterness and weird or obstructive behaviour.
These considerations feed an even deeper malaise in the life sciences. In its disciplined way of looking at the natural world, any branch of science requires its practitioners to act as if they were observers, not participants. In all sciences, the first and last scientific instrument, the one that must be used in every experiment, is the scientist's brain. Scientists who choose human biology as their playing-field cannot fully meet the requirement that they observe their systems dispassionately, without dislodging themselves from their own bodies and minds.
The strain of trying to meet a standard of cool curiosity without flying apart into pieces imposes an unbearable distance between the biologist and his or her own biology. To relieve this strain, medical scientists have created the myth that their instruments and procedures somehow free them from the boundaries of their minds and bodies. This is the myth of absolute rational control of the scientist over her or his material, the notion that the metaphor of scientist as sculptor will not break down even when the sculptor and the sculpture are one and the same.
The conscious expression of this unconscious dilemma is a novel transformation of every scientist's dream of winning. Medical science, like any other science, is profoundly respectful of the score-card, allocating recognition only for precedence in demonstrating the correctness of a new model for how a piece of nature works. The dream of winning takes on an obsessive quality in the medical sciences once the subject of scientific study becomes the mind and body, and the reality of bodily mortality becomes unavoidable. The obsessive response to the certainty of biological death is the promise that a big enough win in the game of science will beat death itself, by conferring a form of immortality on the winner.
Discoveries that set the agenda for the future work of many other scientists do this after a fashion, permanently associating a lower-case version of a scientist's name with an aspect of nature: think of darwinian evolution or the watson-crick model of DNA. But in the medical sciences, belief in winning immortality of any sort is problematic, as it denies the biological reality only too plain from the data, that the eventual loss of self is inevitable.
I first saw how the life sciences could be driven by a fantasy of institutional scientific immortality quite early in my career, about 25 years ago, in a formative, odd conversation with Al Hershey, the Nobel prizewinning geneticist who had used a food blender and some radioactive bacteria in the late 1940s to show that the DNA of a virus - and not its protein coat - was its genetic material. Hershey told me his vision of heaven: you come into the lab every day forever, you do the same experiment you did the day before but with one small variation, and the results are just as exciting, important and new as they were the first time.
This notion of a model so interesting that testing it over and over again wins the game without any further creative thought, is also a product of the root fantasy of the biomedical sciences. Hershey's heaven cannot exist for students of life because they must deal with the facts of life: the first of these is the inevitability of death, the personal mortality of the experimenter. Hershey's myth serves the same function for those biologists who believe in it, as other myths about death serve in other religions: to keep their believers from having to confront this irrational, unbearable reality.
Only faith or obsession - if they are not the same - can expect a method of observation of nature and the knowledge it yields, to set a person apart from the passage of time with its inevitable instant of personal ending. The underlying fantasy, that omnipotence of thought will bring immortality, is a notion inadmissible to rational analysis. This why the conscious, operational agenda of the life sciences masks the fantasy in the metaphorical cloak of institutional immortality.
The thinnest membrane of denial separates the notion of scientific immortality through priority of discover from the deeper, older and wholly non-scientific dream of escaping one's own inevitable death. Personal mortality puts biologists in a quandary every time denial fails: to play the game well, they must never stop asking questions about our mortal bodies, but to play it with their own lives is to be sure that the answers - their own answers, their own models - are sometimes going to be truly frightening. Denial of the fear of nature's terrible power of mortality; projection of the suppressed wish not to be subject to nature, into a vision of nature as capable of bestowing immortality: these are the marks of a masked unconscious operat1ng to create a biomedical science at war with its own stated purposes.
Visions like Hershey's heaven can have unexpected power when they are believed by the people who set the priorities of basic biomedical research. For example, many excellent scientists - their eyes fixed on their place in Hershey's heavens - have become completely averse to the idea that their work should be directed towards any goal beyond their own need to know the answer to their next experiment. Filled with this conviction, and thereby sustained in their faith that they have avoided the fact of mortality, they are easy prey to the habit of making promises to themselves, and to the rest of us, that they cannot keep, promises that hint that death itself may be put off indefinitely. It is not that science and medicine wish to avoid finding cures for diseases, it is that they are too strongly motivated by an irrational, unconscious need to cure death, to be fully motivated by the lesser task of preventing and curing disease simply to delay for a while the inevitable end of their patients' lives and, by extension, their own inevitable end.
About five years ago I decided to act on these observations: I resigned from my laboratory, which had been funded without interruption by the US National Institutes of Health and other government agencies for many years. I continue to write about the medical sciences, to teach the subject to undergraduates and graduate students, and to review manuscripts and grants. Instead of directing the work of a laboratory of my own, I am a consultant in the private sector, helping the research programme of AMBI Incorporated, a biopharmaceutical corporation.
Making this transition successfully is like crossing a highway on foot: oncoming drivers cannot afford to stop, unless they get into an accident themselves, and have to join you walking. Worse than being invisible (when I won a Guggenheim fellowship for my writing, one of my colleagues asked me, what's a Guggenheim?) is being condescended to: I recall the concerned, whispered attempt by a colleague to put me at ease by assuring me that I had simply entered scientific menopause.
Eventually, I learned what smart women already know: menopause has its new freedoms, and even its pleasures. In terms of scientific morale, perhaps the most important of these is the discovery that it is possible to remain a scientist without running a laboratory. The mix that works for me involves writing, teaching, consulting and advising. My first book on science for the general public, Signs of Life (Houghton Mifflin, 1994), takes as its argument the notion that DNA is not merely an informational molecule, but is also a form of text, and that therefore it is best understood by analytical ways of thinking commonly applied to other forms of text, for example, books.
I am now completing my second book, on the difference between the outward, stable, inexorable time of science, and the inward, multiple, flexible time of consciousness, and the consequent problems science has in making sense of consciousness, and of that nasty diamond at its centre, each conscious person's knowledge of inevitable, personal immortality. These books have both been exercises in seeing patterns from insufficient data, and in that sense they are much like the science I used to do; the main differences are that I now write for the public rather than for a star panel of secret reviewers, and that I get paid by a publisher who pays taxes, rather than by a government agency spending tax money.
Having assembled this life for myself in the absence of any structures within the scientific community, I firmly believe that the crisis in morale among today's scientists - in my field, at least - stems not from money problems, nor from the stage of development the field is in, but from a failure by the scientists concerned to form themselves into proper, humane communities. It is never too late to begin the task of forming these communities, to introduce social structures that ameliorate the morale-puncturing competitiveness and anomic individualism of today's basic science, without in any way diminishing the intellectual rigour of the science itself.
No matter how porous the boundaries get between university-based and commercial-sector science, universities are likely to remain the main, if not the sole, source of new generations of scientists for a long time to come. For that reason alone, any changes in the social structure of science will need to take place among university professors in their departments, or else they will not have any lasting effect. We professors might as well begin our reforms in the most conservative way, by rediscovering and rededicating ourselves to the meaning of the title we hold. To "profess" means openly to affirm. Affirmations are matters of the heart. Professors do not deserve the title, unless they are willing to take the time and make the effort openly to affirm something beyond their data, as data speak for themselves and need no affirmation. To be a professor, it seems to me, one must first have something of importance to oneself that needs affirming, and then one must affirm it. I affirm, for instance, that unconscious desires and fears, as well as data sets, drive the agendas of modern molecular biology.
Robert Pollack is in the Department of Biological Sciences, Columbia University, New York, New York 10027, USA (e-mail: email@example.com).
This article is based on the George Washington University symposium "Science in Crisis at the Millennium" on 19 September 1996.
Source: Nature Vol 385 20 February 1997 illustration by Andrew Birch
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