You’re Looking Very Well

by Lewis Wolpert

  In Back to Methusaleh by George Bernard Shaw, immortality is important. The framing conception is that only the extreme longevity of Methuselah and other biblical patriarchs could provide humanity with the necessary wisdom for self-government. Shaw’s solution is enhanced longevity: we must learn to live much longer. Yet earlier he wrote in Misalliance: ‘After all, what man is capable of the insane self-conceit of believing that an eternity of himself would be tolerable even to himself?’

  In Jonathan Swift’s novel Gulliver’s Travels (1726) the name Struldbrugg is given to those humans in a special nation who are born apparently normal but are in fact immortal. Although they do not die, they do nonetheless continue ageing. Swift’s work depicts the evil of immortality without eternal youth, like the Tithonus legend. They are normal human beings until they reach the age of thirty, at which time they become dejected. Upon reaching the age of eighty they become legally dead, and suffer from many ailments including the loss of eyesight and hair:

  They were the most mortifying sight I ever beheld, and the women more horrible than the men… At ninety they lose their teeth and hair, they have at that age no distinction of taste, but eat and drink whatever they can get, without relish or appetite… In talking they forgot the common appellation of things, and the names of persons, even of those who are their nearest friends and relations… and whenever they see a funeral, they lament and repine that others have gone to a harbour of rest, to which they themselves never can hope to arrive. The reader will easily believe, that from what I had heard and seen, my keen appetite for perpetuity of life was much abated. I grew heartily ashamed of the pleasing visions I had formed, and thought no tyrant could invent a death into which I would not run with pleasure from such a life.

  So if we wish to live longer we would like to be sure that we remain healthy and able to look after ourselves. Statistics show that currently the number of years a person can expect to live in poor health after the age of 65 is about five years. This means that somehow the bad effects of ageing must be prevented.

  There have been many attempts to increase the length of life and avoid ageing. Towards the end of the nineteenth century the distinguished neurologist Charles-Édouard Brown-Séquard, at the age of 70 years, found that he was getting tired at night and introduced the first testicular-extract injections for rejuvenation. He advocated the hypodermic injection of a fluid prepared from the testicles of guinea pigs and dogs as a means of prolonging human life. This led to the Russian Serge Voronoff introducing ‘monkey-gland’ transplants to rejuvenate the ageing rich, as he believed that ageing was due to the slowing down of endocrinal secretions. In Kansas, John R. Brinkley’s virility rejuvenation cure—transplanting goat gonads into ageing men—took the nation by storm. These are the historical precursors to the modern use of hormone replacement therapy, testosterone, for tiredness in males. A Swiss clinic from the 1930s injected organs from sheep embryos into patients’ buttocks at a high cost; clients included, it is claimed, Churchill, Eisenhower and Pope Pius XII, but there is no reliable evidence that it worked.

  It is widely held that a restricted but good diet, containing vegetables, fish, and fruit, together with exercise and having a positive attitude about ageing, can contribute to healthy and lengthy ageing. ‘Blue Zones’ is a name given to places where people live longer, healthier lives; although many of the claims are exaggerated, in all of these regions elderly people are much more active and youthful as they follow the rules for healthy ageing. Blue zones include Okinawa, in Japan, the most well-documented and studied population of centenarians, and the Hunza Valley in Pakistan. Legend has it that the Hunza people routinely live until 90 in good health, with many living as long as 120. They eat a diet primarily made up of fruits, grains and vegetables. The Vilcambamba in the southern region of Ecuador are reported to reach 100 and beyond, an achievement attributed to the natural mineral water.

  A hormone secreted by the adrenal gland is half the level in men at age 60 compared to when they were 30. This reduction could be responsible for some of the ageing processes, but attempt to raise the levels in the old have not had useful effects. A number of other hormones, including growth hormone, testosterone, oestrogen and progesterone, have been shown in clinical trials to ameliorate some of the physiological changes associated with human ageing. No hormone, however, has been proved to significantly slow, stop or reverse ageing. It is possible that low testosterone could be the cause of tiredness, depression and sexual weakness in old men. Growth hormone is produced by the pituitary gland—a small structure at the base of the brain—that is necessary for childhood growth, and also helps maintain tissues and organs throughout life. Beginning in middle age, the pituitary gland slowly reduces the amount of growth hormone it produces. Some reports suggest that growth-hormone treatment of elderly individuals can lessen some of the negative physiological changes observed with advancing age, but the results in humans have been controversial. Advertisements claim that by supporting the body’s own natural production of growth nutrients, a human growth hormone such as Sytropin can have dramatic effects: ‘If you are not completely satisfied, simply return for a full refund! It can help you maintain vigour, energy, and youthful enthusiasm. It provides a natural source of essential growth nutrients to assist the body’s ability to withstand some of the harsh effects of ageing.’ There is little evidence for this, or that taking this supplement promotes either longevity or an increased quality of life.

  Dame Linda Partridge is a geneticist who studies the biology and genetics of ageing. I asked her how well we are doing:

  I think we understand it a lot better than we did because we have at last found a way in through the mutations in single genes that can extend lifespan in laboratory animals. This is a major discovery that started with the nematode worm and the longer lived worms remained healthy. Will those genes extend our lifespan? Probably yes as these genes can extend the lifespan of mice, and looking at old humans it seems similar processes are involved, like the insulin signalling pathway. It is not so much the increase in lifespan, but they keep the animal healthy as it ages and it covers a very broad spectrum of age related diseases, and so it’s not just that they do not get cancer or cardiovascular disease but they also get less osteoporosis, their skin is better. This is not what we expected to see. And it is jolly good news.

  We need to make sure that this does help people. Not enough money is going into ageing research. The public needs to understand the advances and that it is a very good area to fund.

  A possible problem is the relationship between scientists and clinical scientists, because geriatrics is mainly concerned with primary care and it is not very popular with students and does not have a strong research base. This means that it will probably be introduced with some medical speciality like endocrinology, cardiology or neurology. Pharmaceutical companies will make the connection—drugs will be the way in. It is most unlikely that it will involve modifying the genome. And one may have to take drugs for rather a long time as one is looking for prevention and so people will start taking the drug when they are middle-aged, and then continue for the rest of their lives—so the drugs have to be very safe. Life expectancy will probably continue to increase by two and a half years a decade. Immortality by altering our genes is beyond the limits of my imagination.

  There is no evidence yet that dietary restriction helps with respect to ageing. When I meet people who are trying it they seem unhappy—their body temperature drops 2 degrees. Exercise is enormously beneficial to older people and quite simple exercise can make a significant difference to general mobility. I run two to three times a week—about 4 miles. I have found my ageing to have some enormous benefits and one or two irritations. One is into a health lottery with ageing and it depends on how that goes. I have been lucky as I have done nothing to look after my health. I do not think as fast as I use to, but enjoy the benefits of being more relaxed.

  Getting rid of all diseases would, it is claimed, increase lifespan
by adding only some 15 to 20 years to the current 80. For much longer lifespans, the ageing process in the cells and tissues itself would have to be reduced. There have been attempts to move in that direction, but even if immortality is not possible, can old age at least be delayed? The secret of long life is not known, and may not exist, but exercise and a good and varied diet seems to help. A study of 17,000 men from Harvard university over 30 years found that moderate exercise increased life by one or two years. Exercising regularly keeps the individual slim and fit, reduces stress, and increases the cardiovascular capability.

  Evidence from animals is that limiting food intake, just eating less, can significantly extend the lifespan. When rats are kept in the laboratory under pleasant conditions but with an intake of food such that after weaning they get 50 per cent less than their well-fed neighbours, they live about 40 per cent longer. The oldest rat with high food intake is around 1,000 days old but there are those on the restricted intake who get to 1,500 days—50 per cent older. In female rats, the age at which the ability to reproduce is lost is extended from 18 months to 30 months. Vitamins and minerals must be included in the diet, but it does not matter if the reduced calories come from carbohydrates, proteins or fat.

  Dietary restriction can increase mice longevity but can impair immunity and wound healing. Low intake of calories suppresses most of the diseases common in older animals such as cancer, high blood pressure and deterioration of the brain. If the restricted feeding regime is returned to full feeding, the ageing process then seems to be actually accelerated. Monkeys on a restricted diet were three times less likely to get age-related illnesses. At the end of the study half of those on a normal diet had died, while for those on a restricted diet it was only one in five.

  Considerable effort is being devoted to understanding the molecular events mediating lifespan extension by dietary restriction, and whether sirtuins are involved. Many more studies in relation to dietary restriction are required for humans as there are negative side effects. A possible way to slow ageing would be to reduce metabolism by blocking receptors for insulin and growth hormone.

  Evidence that humans could also delay ageing by reducing calorie intake comes from Japanese island of Okinawa, where there are probably more centenarians per 100,000 than anywhere else in the world. The average adult food intake is, for cultural reasons, 20 per cent less than the Japanese average, and schoolchildren on Okinawa eat less than two thirds of that recommended in Japan. The death rates from stroke, heart disease and cancer are only about two thirds that for Japan as a whole, and the death rate for 60-year-olds is half the national average.

  Humans practising calorie restriction would reduce their calorie intake by about one quarter. For example, a person who needs 2,000 daily calories for weight maintenance might eat 1,500 to 1,600 calories a day on a calorie restriction diet. Eating so little might greatly increase lifespan, but who would want to live on just 1,600 calories a day? A single hamburger has 1,200 calories. But with the increasing prevalence of obesity, insulin resistance and type 2 diabetes, interventions targeting weight reduction and glucose control should be emphasised. Recent studies on the effects of lowering low-density lipoprotein cholesterol levels have shown a substantial reduction in mortality from coronary heart disease and nonfatal myocardial infarction rates, with a persistent effect in patients older than 75. Subjects with exceptional longevity and their offspring have significantly greater high-density lipoprotein, which reflect their general health and cognitive function performance. Rich diets shorten lifespan not because of excess calories but for more complex reasons—there is a dietary imbalance between fecundity and lifespan, each being maximised at different optimal nutritional levels. Certain amino acids—the structures from which proteins are built—can shorten lifespan in the fly but increase fecundity. This is a complex issue that is not yet solved.

  Avoiding dementia, particularly Alzheimer’s, is a key problem if life is to be extended, as this afflicts one in twenty of those over 65. Researchers from the Institute of Psychiatry in London say that every extra year worked delays the onset of dementia by just over a month. So working until you are 70 instead of 65 is likely to give you an extra six Alzheimer’s-free months. I am not sure that is enough of a benefit to warrant the additional effort, but extending your working life is not the only thing you can do to protect yourself. The research supports previous theories that keeping the mind active for as long as possible can help to postpone mental decline. In contrast to earlier studies, however, the researchers found that the quality or duration of men’s education or the type of work they did had no impact on the age of onset of the disease.

  A community of elderly people in New York with an average age of 77 were monitored for five and a half years. Standard neurological and psychological tests for Alzheimer’s were undertaken every 18 months. Higher physical activity was found to reduce the risk of Alzheimer’s by a third, while people who had a Mediterranean-style diet rich in fruits, vegetables, cereal and fish, but low in meat and poultry, showed a 40 per cent risk reduction. Participants who both exercised a lot and ate a Mediterranean-style diet had a 60 per cent reduced risk. So probably the best way to reduce the risk of dementia is to combine keeping physically active with eating a balanced diet, and getting blood pressure and cholesterol checked regularly.

  Another study found that adults who ate fish a few days per week were almost 20 per cent less likely to develop dementia than those who ate no fish at all. Although drinking coffee had previously been linked to a lower risk of developing Alzheimer’s, a more recent study suggests that caffeine can directly target the disease itself. Mice with a rodent equivalent of the disease showed a 50 per cent reduction in levels of amyloid protein in their brains after scientists spiked their drinking water with caffeine. A small amount of alcohol can also help, but 10 per cent of cases of dementia are due to too much drink.

  Attitude to ageing can itself have an effect and a positive attitude can extend life by some five years. In 1968 a team studied a group of people, who were aged 18 to 49, who completed a questionnaire that measured the extent to which they agreed with 16 negative views of ageing. These included beliefs that elderly people are ‘feeble’ and ‘helpless’. Thirty years later, 25 per cent of those who had negative beliefs about ageing had suffered heart disease or a stroke, compared with 13 per cent of those who rejected the such views. Those who viewed ageing as a positive experience lived an average of seven and a half years longer. Women who were optimistic about their future were 14 per cent less likely to die from any cause than pessimists, and 30 per cent less likely to die from heart disease after eight years of follow-up in the study. Further evidence for the positive role of mental activity comes from a study of nuns who had long lives, even though they had plaques of amyloid characteristic of Alzheimer’s disease in their brains. Positive self-perceptions of ageing have a greater impact on survival than lowered blood pressure or cholesterol. On the other hand, there is some evidence that stress, particularly short-term stress, can be beneficial and help reduce the ageing process, including Alzheimer’s. A very provocative contemporary view is that laziness and lack of exercise and ambition will extend the lifespan.

  Though thousands of years old the ancient Taoist tradition of eating mushrooms and other magical substances together with eating less, as some wandering monks practised in India to extend life, is still with us. There are modern religious mystics who believe in the possibility of achieving physical immortality through spiritual transformation as a part of their religious doctrines. They believe that after God has called the Day of Judgment, they will go to what they describe as Mount Zion in Africa to live in freedom for ever. They avoid the term ‘everlasting life’ and deliberately use ‘ever-living’ instead. An example is the Rastafarian and Jamaican singer Bob Marley, who refused to write a will despite suffering from the final stages of an advanced metastasised cancer on the grounds that writing a will would mean he was ‘giving in to death’ and forgoi
ng his chance of living for ever. A group called the Rebirthers believe that they can acquire immortality by following the ‘connected’ breathing process of rebirthing.

  The multi-million-pound industry based on anti-ageing treatments is discussed in the next chapter. In 2002 an article in Scientific American supported by some fifty scientists stated that the more dramatic claims made by those who advocate anti-ageing medicine in the form of specific drugs, vitamin cocktails or esoteric hormone mixtures are not supported by scientific evidence, and it is difficult to avoid the conclusion that these claims are made for commercial reasons. There has been a resurgence and proliferation of healthcare providers and entrepreneurs who are promoting anti-ageing products and lifestyle changes that they claim will slow, stop or reverse the processes of ageing.

  The American Academy of Anti-Aging Medicine promotes the field of anti-ageing medicine and trains and certifies physicians in this speciality. Their co-founder Ronald Klatz stated that ‘We’re not about growing old gracefully. We’re about never growing old… The leaders of the Anti-Aging movement will help to usher in a new modern age for humanity: The Ageless Society. There is a remedy for this apocalypse of aging, and this remedy comes just in time to save America.’ But there is scientific hostility to its practices and no evidence that what they promote works.

  Medical interventions for age-related diseases do result in an increase in life expectancy, but none have been proved to modify the underlying processes of ageing. At present there is no such thing as an anti-ageing intervention. For example at present there is relatively little evidence from human studies that supplements containing antioxidants lead to a reduction in the rate of ageing. The use of cosmetics, cosmetic surgery, hair dyes and similar means for covering up manifestations of ageing may be effective in masking age changes, but they do not slow, stop or reverse ageing.