‘Every Man desires to live long; but no Man would be old’
How long can we, and should we, live? How to live for ever has been a compelling subject for a very long time. One of the earliest legends about immortality, and also one of the earliest written stories, is that of Gilgamesh, the Babylonian demigod, from around 2000 BC. When he aged and began to fear death, Gilgamesh was told that he could survive forever if only he could show that he could master sleep by not sleeping for seven days and nights. But try as he might, he failed to do this. The gods then told him that he could find a plant underwater that, if he ate it, would make him alone immortal. Gilgamesh found the plant, but was enjoying swimming so much that he left the plant on the shore while he continued swimming. A snake came along and ate the plant. The lesson to be learned was that ageing was unavoidable.
The legends of the Greeks are filled with the adventures of the immortal gods and humans who seek immortality through their deeds, or through the acts of the gods. But there was also a more realistic attitude. The Greek philosopher Democritus criticised people for yearning for a long life, and argued that if they developed the right attitude to ageing and death they could live more peacefully. The Roman Lucretius thought it absurd not to recognise that a long life was insignificant compared to how long one remains dead. He also argued that death was essential to keep the population down.
The ancients were all too aware of the dangers of immortality if the effects of ageing were ignored. This is illustrated by the story of Tithonus in Greek mythology, a story we should keep in mind when trying to extend life. Tithonus was the lover of the goddess of dawn, Aurora, and so good at what he did for her that she went to her father, the god of gods, Zeus, and asked if Tithonus could have eternal life. Zeus, being a doting father, immediately granted Tithonus immortality. The problem was that Aurora had failed to also ask for him to have eternal youth. With time the ageing process took its toll, and when Tithonus reached a hundred he had mild cognitive impairment and went around Aurora’s castle babbling incessantly:
But when loathsome old age pressed full upon him, and he could not move nor lift his limbs, this seemed to her in her heart the best counsel: she laid him in a room and put to the shining doors. There he babbles endlessly, and no more has strength at all, such as once he had in his supple limbs.
Aurora no longer loved him, and one day she turned him into a grasshopper, a cicada. Some claim that when today we hear the chirping of cicadas, it is just a group of old men babbling incessantly.
Judaism and Christianity had very strong views about long life. The Bible is against immortality; Psalm 90, verse 10, sets the human lifespan at threescore and ten, though the possibility of 120 years is given in Genesis. When Adam and Eve had eaten fruit from the tree of knowledge, God said, ‘See! The man has become like one of us, knowing what is good and what is bad! Therefore, he must not be allowed to put out his hand to take fruit from the tree of life also, and thus eat of it and live forever.’ God banished them from the Garden of Eden and stationed the cherubim and the fiery revolving sword to guard the way to the tree of life.
Old age could be the reward for a moral life and an indication of God’s favour. ‘Follow the whole instruction the Lord your God has commanded you, so that you may live, prosper, and have a long life in the land you will possess.’ ‘Ye shall harken diligently unto my commandments that your days may be multiplied, and that of your children,’ says God in Deuteronomy. And in Proverbs: ‘The fear of the Lord prolongeth days: but the years of the wicked shall be shortened.’
There are, nevertheless, claims in the Bible for very very long lives: Adam lives for 930, Noah 950 and Methuselah 969 years. Methuselah was a Hebrew patriarch and the grandfather of Noah; not much is known about him other than his extraordinary lifespan. There is also a figure from medieval Christian folklore whose legend began to spread in Europe in the thirteenth century, the case of Ahasverus, a Jewish cobbler, who told Christ to move on when he was carrying his cross and needed help. Christ told him that he would move on, but condemned Ahasverus to wander the earth and for his clothes to remain intact till Christ returned. And every 10 years he would be rejuvenated. There were reports that this Wandering Jew had been identified in 1252 at the Abbey of St Albans, and then again in Hamburg in 1642.
Many Indian fables and tales concern the ability to jump into another body—performed by advanced Yogis in order to live a longer life. There are also entire Hindu sects, the Naths and the Aghoras, devoted to the attainment of physical immortality by various methods. Long before modern science made such speculation unreasonable, people wishing to escape death turned to the supernatural world for answers. Examples include Chinese Taoists and the medieval alchemists and their search for the Philosopher’s Stone.
Denial of ageing can be very common, and longevity myths have been around for as long as humanity. Many of these legends involve places where people are reputed to live long. While it is true that people in certain cultures do not suffer many chronic illnesses while ageing, the lifespans of people in these places are hard to verify. As the Guinness Book of World Records stated in numerous editions from the 1960s to 1980s, ‘No single subject is more obscured by vanity, deceit, falsehood, and deliberate fraud than the extremes of human longevity.’
There were claims that Thomas Parr was the oldest man who ever lived, surviving till 152 years. He was said to have been born in 1483 near Shrewsbury. He did not marry until he was 80 years old and had two children, a son and a daughter, both of whom died in infancy. He attributed his long life to his vegetarian diet and moral temperance, although when he was around a hundred years old he allegedly had an affair, and a child born out of wedlock. As news of his age spread, ‘Old Parr’ became a national celebrity and was painted by Rubens and Van Dyke. In 1635 he was brought to London to meet Charles I. In London he was treated as a spectacle, but the change in food and environment apparently caused his death. Charles I arranged for him to be buried in Westminster Abbey in 1635. William Harvey, the physician who discovered the circulation of the blood, performed a post-mortem on Parr’s body. His autopsy suggested that Thomas Parr was under 70 years old.
In around 1500, Alvise Cornaro, an Italian nobleman aged 40, was feeling very unwell, and was advised by his doctor ‘cut down on your riotous living, stop the drinking, cut out the rich food, eat as little as you can, and don’t abuse your body. You can get well.’ He wrote The Art of Living Long and argued that men and women were not destined to die at 60 or 70, but with care and a good constitution could live extremely long lives. The key to longevity lay in giving up excesses in all things, and he preached extreme moderation. He died aged 102.
Legends about healing waters abound. People have always talked about, and hoped for, water that will restore youth and health. Herodotus, the Greek historian who lived in the 5th century BC, provided much information concerning the nature of the world and the status of the sciences during his lifetime. He referred to a fountain containing a very special kind of water located in the land of the Ethiopians, and he attributed the exceptional longevity of the Ethiopians to this water. Tales of healing waters are also linked to Alexander the Great in his search for the Water of Life. Travelling almost to the edge of the world, Alexander finds a darkened country and travels in it with his servant Andreas. Alexander can’t find his way through the darkness, but his servant does. Andreas drinks of the Water of Life and becomes immortal.
Another example that gave rise to the idea of a Fountain of Youth comes from the natives of Hispaniola, Puerto Rico and Cuba, who told the early Spanish explorers that in Bimini, a land to the north, there were waters that had such miraculous curative powers that any old person who bathed in them would regain his youth. Juan Ponce de Leon, who had been with Columbus on his second voyage in 1493, and who had later conquered and become governor of Puerto Rico, is supposed to have learned of the fable from the Indians. The fable was not new, and probably Ponce de Leon was vaguely cognisant of the fact that such waters had been mentioned by medieval writers, and that Alexander the Great had searched for such waters in eastern Asia. Ponce de Leon, who had become wealthy in the colonial service, equipped three ships at his own expense and set out to find the mythical fountain that would restore his health and make him young again. What he found was not Bimini but Florida, and now many patients clearly believe he was successful, as during the winter months they eschew the care of their good doctors and flee south to Florida’s warmer climate.
Myths about extreme old age persist into modern times. The Abkhasia are a people living in the Caucasus Mountains in southern Russia, a mountainous area near the Iranian border. They have a reputation for extremely long and healthy lives. In the 1960s and 1970s claims were made for lifespans of 150, marriages at 110 and fatherhood at 136. The greatest claim was that one man, Shirali Muslimov, was 168 years old when he died in 1873. The Soviets honoured him with a postage stamp. An official passport listed his birth date as 1805; Muslimov had no known birth certificate. The story was taken up by National Geographic Magazine, which later recanted on the claim. Individuals claiming to be physically immortal include Comte de Saint-Germain; in eighteenth-century France, he claimed to be centuries old, and people who adhere to the Ascended Master Teachings are convinced of his physical immortality. An Indian saint known as Vallalar claimed to have achieved immortality before disappearing for ever from a locked room in 1874.
Senescence results from a cumulative imbalance between damage and repair. Progress in reducing damage by improving living conditions and preventing disease, together with medical interventions, are fundamental causes of increased longevity. But myths apart, only around fifty people in human history have been verified as reaching the age of 114. Fewer than twenty of those who got to 114 have reached the age of 115. Worldwide there are estimated to be between 300 and 450 living supercentenarians—that is, over 110 years old—but as of June 2010 there is a list of only 79 validated supercentarians, and only three are male. Just how content they are is not clear.
Currently the oldest person is a Japanese lady Kama Chinen who is just short of 115 years. The title of the oldest verified person in history belongs to Frenchwoman Jeanne Calment (122 years and 164 days old), who died on 4 August 1997. She was born in Arles, France on 21 February 1875. Her genes may have contributed to her longevity as her father lived to the age of 94 and her mother to the age of 86. She rode a bicycle to the age of 100 and smoked till she was 117.
While the oldest woman was 122, the oldest man so far was 115. He was Christian Mortensen (1882–1998), a Danish-American whose age is undisputed, although the Guinness Book of World Records still ranks him second to the disputed case of Shigechiyo Izumi, 120, as the oldest man ever. Recently the oldest man alive, Henry Allingham, died at 113 in July 2009. There was much in the news about him; he had 6 grandchildren, 12 great grandchildren, 14 great-great grandchildren, and one great-great-great grandchild. He had had two mental breakdowns caused, he claimed, by working too hard. He lived in a home for blind ex-servicemen.
New evidence studying the genomes of 1055 centenarians found that it is now possible to predict if someone can live to 100 with a 77 per cent accuracy. The result is based on analysis of 150 mutations. It was found that 90 per cent of the centenarians possessed a particular genetic signature of mutations in the relevant genes. However, one must remember that this genetic test will not tell someone how long they will live, as genetics only accounts for about a quarter or a third of our lifespan; it could tell someone how long they might live.
The oldest known mothers are thought to be two Indian women, Rajo Devi and Omkari Panwar, who were allegedly both 70 when they had babies in 2008 following fertility treatment. But neither has a birth certificate to verify their age. The world’s oldest father, Indian farmer Nanu Ram Jogi, fathered a child in 2007 at the age of 90. He is married to his fourth wife, boasts he does not want to stop, and plans to continue producing children until he is 100. Mr Jogi admits he is not certain how many children his series of four wives have borne him—but counts at least 12 sons and nine daughters and 20 grandchildren.
Alice Sommer was born in Prague 106 years ago and is the oldest person I know. She lives very close to me and is famed as a piano player and teacher—she still plays for several hours a day. She lives alone in quite good health, but goes out little, usually taken by her grandson. When asked how she felt about being old she replied:
There are very good things. Experience. Looking backwards and enjoying knowledge. Only when we are so old can we appreciate the beauty of life. We are surrounded by miracles. Memories are so important. There are no bad things about growing old. None at all, and I am not at all afraid of death as that is the natural order of things. I was lucky to have been born with a very good temperament. When I am faced with a bad situation I immediately find something good in it. I do not think about how old I would like to get.
How is she cared for?
I am looked after extraordinarily well—a girl comes in the morning for half an hour and then another for half an hour in the evening. And I get meals on wheels from the council. I use a magnifying glass to read so do not read much but Bach is my philosopher of music.
Those who pass beyond 90 do seem often to cope well, and centenarians can have daily lives that are as good as those ten years their junior. Being independent is a strong indicator for living long. In several studies, over one third of supercentenarians were still independent and able to care for themselves. In general it seems that this very old group are less well than the younger old, but then come to death rapidly. For example, only about 4 per cent die of cancer compared to 40 per cent of those around 50. They also have very low rates of heart disease, though there are stories that some are smoking heavily. There is a high incidence of some form of dementia, but not Alzheimer’s, though their brains have the signs of that disease.
Of those who reach 100, a study found that about one half avoided chronic disease till they were over 80, and about one fifth escaped all the main chronic diseases. Children of centenarians suffer less from cancer and heart disease. A variation in the gene FOXO3A, a key regulator of the insulin-IGF1 signalling pathway, has a positive effect on the life expectancy of humans, and is found much more often in people living to a hundred and beyond—this appears to be true worldwide. The ApoE gene can also help with respect to dementia. Failing to give up smoking or to control blood pressure and cholesterol were reported to reduce life expectancy by 10 to 15 years. However, Clement Freud commented: ‘If you resolve to give up smoking, drinking and loving, you don’t actually live any longer, it just seems longer.’
Studies of twins and long-lived families have indicated that genes can explain about one third of maximum lifespan, but even identical twins age differently and this may be partly due to random switching on and off of some of their genes due to environmental influences. The other determinants are how one lives and chance factors like accidents and infections. Siblings of centenarians have a significantly higher chance of becoming a centenarian themselves. We have seen that the insulin IGF-1 system is involved in determining lifespan in model organism, so could reduction in its activity increase lifespan in humans? The answer seems to be yes. Mutations known to impair IGF-1 receptor function are overrepresented in a cohort of Ashkenazi Jewish centenarians, and DNA variants in the insulin receptor gene are linked to longevity in a number of groups located throughout the world. Increased activity of sirtuins, related to ageing in yeast, prompted by the drug resveratol has not been shown to extend lifespan in mammals.
In model organisms, such as the worm, fruit fly and mouse, changes in genes can dramatically increase their lifespan as much as fivefold. The equivalent life-extending effect in humans would result in an average lifespan of 400 years, and a maximum lifespan of over 600 years. But how healthy would such individuals be, and would they not have the effects of ageing? Never forget Tithonus. Many of the pathways regulating lifespan in model organisms are conserved throughout evolution, yet the genes that could dramatically increase human lifespan have not been identified.
How long would we like to live? Polls show that on average people want to live to about 90, though some 15 per cent had no idea how long they wished to live. Many were rightly very concerned about health as they aged, and one half, for example, feared the inability to drive their car. The elderly were less fearful than the young. Only about half of the public want scientists to work on mechanisms of age extension.
The Japanese artist Hokusai made his famous wood-block print of The Great Wave off Kanagawa in the 1820s at the age of around 65. Even after reaching the age of eighty, he was busy producing many fine prints. He often expressed his desire to live beyond the age of 90, and just before he died at the age of 88 he sighed and said his last words: ‘If heaven gives me ten more years, or an extension of even five years, I shall surely become a true artist.’ He also wrote:
All I have produced before the age of seventy is not worth taking into account. At seventy-three I learned about the real structure of nature, of animals, trees, birds, fishes and insects. In consequence when I am eighty, I shall have made still more progress. At ninety I shall penetrate the mystery of things; at a hundred I shall certainly have reached a marvellous stage; and when I am a hundred and ten, everything I do, be it a dot or a line, will be alive. I beg those who live as long as I to see if I do not keep my word.
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 forgoing 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.
Nevertheless, there is extensive advertising of anti-ageing products and the public is spending vast sums of money on them, even though in most cases there is little or no scientific basis for their promises and some may have harmful side effects. Some scientists are unwittingly contributing to the proliferation of these pseudoscientific anti-ageing products by failing to participate in the public dialogue about the reliable science of ageing research. There are, for example, advertisements for a treatment which prevents shortening of telomeres and so promotes longevity. Although telomere shortening may play a role in limiting cellular lifespan, there is no evidence that telomere shortening plays a major role in the determination of human longevity.
There are a variety of reports of substances that can extend life. A study of over a thousand men in Holland over 40 years found that those who drank half a glass of wine a day lived about five years longer than those who drank no alcohol at all, and two and a half years longer than those who drank beer and spirits. Herbs such as ginseng, rhodiola and maca have active ingredients that are claimed to suppress ageing. Studies show that a plant compound, resveratrol, can extend the lifespan of yeast, worms, flies and fish but there is as yet no evidence that it helps with humans. Resveratrol appears to mediate ageing effects partly by activating sirtuins. Resveratrol is found in the grape plant and in berries, and it is also a vital component of red wine.
A new star has appeared in the field of drugs that delay ageing in laboratory animals, and are therefore candidates for doing the same in people. The drug is rapamycin, already discussed in relation to TOR, its target, and which is in use for suppressing the immune system in transplant patients and for treating certain cancers. It can increase the lifespan of nematodes and fruit flies, and recently increased the lifespan of mice significantly. Given to the mice when they were 600 days old, it increased their lifespan by about 30 per cent. It has not been tested on humans and this should be done with great care because of its effects on the immune system. Studies in mouse models indicate that weakening the pathway on which rapamycin acts leads to widespread protection from an array of age-related diseases.
Aubrey de Grey is a scientist who, contrary to the standard scientific view, believes it will be possible to significantly prevent ageing. He calculates that two thirds of the people who die each day worldwide die of ageing, based on a definition of ‘death from ageing’ as death from causes that afflict the elderly more than young adults. He claims it will be possible to reduce the effects of ageing so greatly that humans will have a 50/50 chance over the next thirty years of being effectively immortal. He believes regenerative medicine may be able to thwart the ageing process altogether within that time. He works on the development of what he has termed ‘Strategies for Engineered Negligible Senescence’, a tissue-repair strategy intended to rejuvenate the human body. One basis for his claim is that mitochondria are damaged due to free radicals damaging their DNA, and they cause their host cells to secrete more damaging free radicals and so damage other cells. He believes that it will be possible to obviate the damage in the mitochondria’s DNA. He also claims that many age-related degenerative diseases are linked to inadequate lysosomal function. Lysosomes are small vesicles in cells whose contents can destroy almost any unwanted cellular material—but not quite all, and this shortfall is known to underlie various age-related problems, including cardiovascular disease and macular degeneration. Alzheimer’s disease involves the failure of unwanted proteins to be destroyed by other waste disposers both inside and outside the cell. Amyloid protein aggregates, a possible cause of Alzheimer’s, are made from a normal protein that has been altered. An anti-amyloid vaccine could be helpful as the immune system would destroy the aggregates. A clinical trial along these lines was stopped when one individual became very ill, but a new trial has now reached phase 3.
In order to prevent ageing in this way, it will be necessary to repair, or else render harmless, numerous types of accumulating molecular and cellular damage so that the age-related pathologies caused by excessive amounts of that damage are prevented. In various cases, this requires manipulating genes, which at present would need to be done in the fertilised egg. And then the researcher would have to wait more than a hundred years to see if that individual survives that long, and suffers no problems from the manipulation to the genes. This is a most unlikely scenario; it is far too risky, and few if any researchers would live to see if their treatment worked. Thus, as de Grey accepts, the comprehensive application of regenerative therapies to ageing within a few decades relies on the development of safe and highly effective somatic gene therapy, which currently remains a daunting prospect. Additionally, an effective panel of therapies must address cancer, extracellular damage causing pathologies such as heart disease, and viral and bacterial infections. Finally, it is also far from clear that preventing cellular ageing would prevent cognitive abnormalities such as dementia and depression occurring, and de Grey acknowledges our ignorance of such matters.
In the UK the life expectancy for men and women is now 77 and 82, and a young man in his 20s today is expected to live five years longer than a man in his 50s. There are estimates that one in eight UK citizens now aged 35 will live to over 100. Half of the children alive today in countries with high life expectancies may celebrate their 100th birthday. In the UK, with a population of 61 million, 400,000 are over 90 and there are more pensioners than children under 16. The small village of Montacute in Somerset has the highest life expectancy for men in Britain, possibly because many of them grow their own food and work hard at it. In the USA, male life expectancy is 75 and female is 81. There is expected to be an increase from 4 million to 20 million over-85s by 2050 in the USA, at which time there may be nearly one million centenarians. At present about 10 per cent of the world’s population is over 60 but by 2050 it will be 20 per cent, and the elderly will outnumber children worldwide. Women outnumber men at age 100 by 5 to 1. Japan has the current highest life expectancy for females, estimated at 85, and Iceland for males, at 80 years.
There are currently about 40,000 centenarians in the United States, and they are the fastest growing segment of the population. Traditionally scientists believed that most people who live to 100 experience a ‘compression of morbidity’—that is, they do not develop common age-related chronic illnesses like diabetes or coronary disease until very late in life, if at all. However, more recently, investigators have found that nearly one-third have in fact suffered from long-standing chronic illness, in many cases for 15 years or more, before turning 100. What they experience is a compression of disability: they avoid major disability and require little or no assistance in performing the activities of daily life, at least until extreme old age.
The increase in the numbers of elderly people throughout the developed world is already having serious consequences, which will only increase in the future. Leon Kass, who has been chairman of the US President’s Council on Bioethics, has questioned whether the resulting overpopulation problems would make life extension unethical. ‘Simply to covet a prolonged lifespan for ourselves is both a sign and a cause of our failure to open ourselves to procreation and to any higher purpose… Desire to prolong youthfulness is not only a childish desire to eat one’s life and keep it; it is also an expression of a childish and narcissistic wish incompatible with devotion to posterity.’ He highlighted the importance of lifespan limits in making room for new generations who deserve to take their rightful place in the world.
Francis Fukuyama, who predicted the eventual global triumph of political and economic liberalism, argues that efforts to increase human longevity risk undermining social security schemes, damaging family structures, and rendering the United States vulnerable to assault by countries with more youthful populations. He suggests that it could lead to a ‘posthuman future’, where human existence would be radically different from what we currently experience. This may be an alarmist view, but the problems associated with increasing human lifespans are still severe.
What impacts might a much further increase in age in the population have? Would immortality be a benefit or a disaster? In Kurt Vonnegut’s 1998 story ‘Tomorrow and tomorrow and tomorrow’ a grandfather aged 172 takes an anti-ageing potion; he drives his descendants mad by taking the best food and space. Many fear that extending lifespan without reducing illnesses would increase the time living with limited physical and mental abilities, but it could nevertheless offer new opportunities. Superlongevity, radical life extension, would require every citizen to learn new skills. There would probably be a craving for novel experiences. Even now, many of those who have retired feel much younger and wish to have an active life that can include new work and learning. Living longer would enable people to find out what the future is like, but they would need to be healthy and cared for—and not be bored. And note again that in spite of all the research, no way of preventing ageing other than by a healthy lifestyle has yet been discovered.
Nevertheless there are several organisations devoted to extending lifespan and even superlongevity. Leon Kass apparently believes that if our bodies don’t grow old we will become even more fearful of death. He also thinks we will feel unhinged and lack the sense of purpose that supposedly comes with growing old. Superlongevity would make time of no consequence and this could have bad consequences due to the increase in population size. The emerging picture of perhaps many hundreds, or even thousands, of small effects and tissue-specific damage provides a sobering challenge for those aiming to engineer reduced senescence. Controlling behavioural and environmental exposures to reduce cell damage may be a more realistic priority, as the great majority of people are likely to have large numbers of genetic vulnerabilities for one or another disease not related to ageing. A £5 million programme of bioengineering has been proposed to do research to find solutions to the problems associated with ageing of the body. Research will focus on joints, spine, teeth, heart and circulation. This seems more sensible than trying to develop safe and effective genetic engineering to alter the thousands of small damaged functions in our cells.
In Shakespeare’s All’s Well that Ends Well the king is suffering from physical disability related to old age. When Helena offers to cure him, which she later does with a potion from her doctor father, the king responds with cautionary words: