Chapter 26
In Search of the Elixir of Youth — Part 1
Latter-day work on the biology of ageing confirms Leclerc’s impressions and provides important clues about how to develop effective interventions that delay ageing. It is now clear that some of the hormonal and cellular pathways that influence the rate of ageing in lower organisms, such as flies or worms, also contribute to many of the manifestations of ageing that we see in humans, such as cancers, cataracts, heart disease, arthritis and dementia. Several studies have demonstrated that by manipulating certain genes, altering reproduction and reducing caloric intake, the duration of life of both lower organisms and mammals can be extended. Lower species are easier to study in large numbers, particularly drosophila, the common housefly. I have visited many laboratories that house large glass containers full of noisy buzzing flies, which are the mainstay of the laboratories research activities into ageing. Much of our knowledge of why human cells age derives from observations in such lower species. Perhaps next time we go to swat a fly, we will pause and reflect on its contribution to science! We humans are very advanced organisms – you have been working on ‘you’ for millennia. You exist only because of billions of deaths of organisms that were less well-adjusted and less complex. You are the survivor – you exemplify ‘survival of the fittest’. You started off your journey 4 million years ago as a single cell. Today’s cells have altered little in core content from that first cell. Cells are very, very tiny. For example, it takes 10,000 human cells to cover a pin head and our bodies are made up of trillions of cells. A cell’s main job is to produce energy, the energy that keeps the cell and therefore us alive. Very simply, food is converted into energy by the cell; waste occurs as a by-product of this energy and is rapidly disposed of by the cell. The instructions for energy creation and for waste disposal come from the cell’s nucleus. As we learned earlier, the nucleus is the cell’s library – a digital library that holds all of the cell’s information and sends out instructions through the cell at regular intervals when required. The cell wall allows the toxins and waste, which are the by-products of energy production from metabolism of food, to leave the cell – and eventually the body via the intestines and bladder as faeces and urine – and keeps all the good chemicals and food within for energy production. So, anything that changes the strength of the wall can cause serious damage. The part of the cell that produced energy and is responsible for the energy transactions necessary for cell survival is the mitochondria. Our cells are constantly busy, they never rest, generating energy and dividing and producing new cells repeatedly. During these divisions, the genes also divide and thereby pass on the instructions for various characteristics to the next generation. Occasionally, there are imperfections in divisions, called mutations. A mutation alters the instructions for one or more characteristics. Some mutations are minor and we live with them unnoticed but many mutations lead to death or impairment of the organisms. In this way, superior organisms, such as you and me, slowly evolved towards greater complexity – we are the survivors. Individual cells have a finite lifespan, so when they die they are replaced by new cells, which is why all division or replication is so important to us. Cells are dying and being replaced all of the time. Anything which interferes with this delicately balanced cycle between cell death and cell reproduction will hinder replacement of new fully functioning cells and thereby contribute to ageing of the organism. The makeup of a human cell
Chapter 7: In Search of the Elixir of Youth
Each type of cell has its own lifespan – this is important in forensic science and in murder investigations. For instance, red blood cells live for four months, white blood cells for a year, skin cells for three weeks, colon cells for four days and sperm cells three days. By knowing cell lifespans, time of death can be surmised depending on which cells are still living.
In natural animal populations, predation, starvation and environmental stresses rapidly eliminate frail or old animals. Humans are the striking exception to this rule, achieving a life expectancy of over 80 years despite frailty and old age. In the last 200 years, the average human life expectancy has doubled in most developed countries. In a century, the world has changed markedly from there being almost no countries where the life expectancy of the average citizen was of 50 years to many countries having a life expectancy of 80 years or more, and the pace that these changes are occurring is extraordinary. The following title made the cover of Time magazine in 2015: ‘This baby could live to be 142 years old’. In 1900 life expectancy of females was 47. In 2010, it was 79 years and continues to rise. You may well ask why this is happening. We don’t have all of the answers but extended lifespan is generally due to the ability of human populations to manipulate their environment, domesticate animals and plants, use tools and fire to provide stable nutrition and almost eradicate parasites. All of this is coupled with advances in medicine, clean water, less stress, more prosperity and, of course, our dominance over mutations as we evolved. The biological consequences and population impact of ageing is thus a uniquely human experience. For example, women will live half of their adult lives after losing reproductive potential – a situation unheard of in the rest of the mammalian world.
Chapter 7: In Search of the Elixir of Youth
We can learn more about what else is contributing to this human longevity from some animal species who live extraordinarily long lives. For most animals, there are two basic ways to die: from ageing and thus disease, and from injury. But a select few species are seemingly immune to ageing or diseases. In these animals, the gradual accumulation of cell damage that eventually kills most cells is slowed down dramatically – almost to a virtual standstill – thus prolonging life and youth. This is referred to as ‘negligible senescence’. It is fascinating how long some of these species live for. Tortoises are the most famous negligibly senescent animals. When an Aldabra giant tortoise named Adwaita died in 2006, carbon dating of his shell confirmed that he was born around 1750 – he was 255 years old. He died of liver failure complicated by a wound brought on by a crack in his shell. If his handlers at the Alipore Zoological Gardens in Kolkata, India, had had the resources and inclination to arrange for a liver transplant and surgery to rebuild his shell, Adwaita would still be crawling around today. Even so, making it to 255 years old wasn’t bad! Average life expectancy in European countries with accurate death records since 1800
Chapter 7: In Search of the Elixir of Youth
The Antarctic sponge has extraordinary longevity, living up to 1,550 years. It hardly moves at all, leading to one of my colleagues cruelly referring to a particularly lethargic member of his team as ‘the sponge’. The bowhead whale, the largest of long-lived mammals, lives over 200 years (the oldest known whale was 211 years). The jellyfish Turritopsis nutricula is the most fascinating of all, transitioning from polyp to adult to polyp, thereby displaying ‘eternal youth’ – the Benjamin Button of the animal world. Spare a thought for the queen termite with a lifespan of 50 years – the poor thing produces 30,000 eggs per day. Contrast this with the female American mayfly, much beloved of fly fishermen, which lives for only five minutes. You can imagine how these extremes in lifespan are of interest to us scientists in gerontology – what is it about the cell functions of different species that drives longer, or shorter lifespan? Were we to understand this and develop the ability to mimic the relevant changes in human cells we would likely be able to slow down ageing and occurrences of disease and thereby extend healthy human life – the much sought-after ‘elixir’. OK, ladies, take a bow, because women live longer than men in almost all modern societies. Longer life in females is not just the case for humans but also for many other mammals, such as chimpanzees, gorillas, orangutans and gibbons, all of whom consistently outlive the males of the group. On average, women live between six and eight years longer but this gap is narrowing in western civilisations, mostly because deaths from cardiovascular diseases are declining in men.
There are a host of other plausible explanations for the gender gap, including biological, hormonal, genetic, environmental and social factors, all of which likely contribute in varied proportions. One popular biological explanation is the gender difference in metabolic rate. Metabolic rate, the amount of energy that we produce from metabolism of food, is about 6 per cent higher in adolescent males than females of the same age and increases to 10 per cent after puberty. In many experiments and in most species, metabolic rate is negatively associated with longevity – that is, high metabolic rate is coupled with a reduced lifespan.