Why Do We Age? — Part 2

She washed herself unassisted with a flannel cloth rather than taking a shower, applying first soap, then olive oil and powder to her face. She washed her own glass and cutlery before proceeding to lunch. She made herself daily fruit salads with bananas and oranges. She enjoyed chocolate and, after the meal, smoked a Dunhill cigarette and drank a small glass of port. At this juncture, I’ll share that my husband, who is partial to both port and a cigar, frequently cites Calment as an example for why his habit may be beneficial rather than harmful, usually when I’m mid-sentence admonishing him for the cigar! In the afternoon, she would take a nap for two hours and then visit her neighbours in the nursing home, telling them about the latest news she had heard on the radio. At nightfall, she would dine quickly, return to her room, listen to music (her poor eyesight due to cataracts, which she refused to have surgery for, prevented her from enjoying her crosswords pastime), smoke a last cigarette and go to bed at 10:00pm. On Sundays, she went to Mass and on Fridays, to Vespers.

Apart from aspirin for migraines she had never taken medicine, not even herbal teas. She did not have hypertension or diabetes and her blood sample analytics in her last year were in normal ranges. Unfortunately, aged 114 she had a fall, sustained a hip fracture and was in a wheelchair thereafter, but lived for almost another nine years. Calment remained ‘mentally sharp’ until the end of her life. A documentary film about her life, entitled Beyond 120 Years with Jeanne Calment, was released in 1995.

Chapter 2: Why Do We Age?

But even Calment’s story did not escape the scrutiny and questioning of the scientific community. In December 2018, Jeanne Calment’s record of longevity was contested by a Russian gerontologist, Valery Novoselov, who was an assistant professor – the first step of the academic ladder – at the University of Moscow, and by Nikolay Zak, a laboratory technician. Their sceptical paper was published on a website, not a peer-reviewed journal, and Calment’s story was also challenged by them in a manuscript posted on ResearchGate.net. The sceptics proposed a fraudulent conspiracy by her family to identity switch between mother and daughter. Furthermore, they contested that it was mathematically impossible to live to Jeanne Calment’s advanced age. Despite the total absence of validation for their claim, and the absence of peer review of their assertions, it created quite a storm in the media and gerontology community. I recall having dinner with a renowned UK gerontologist the night before the claim was made public. He told me with some glee of this amazing story which would ‘break tomorrow and discredit and defame Jeanne Louise Calment and her family’. Even he never thought to question its validity! But the claim was incorrect and was followed up a year later with a verified rebuttal and presentation of full details confirming Jeanne Calment’s age in a proper peer-reviewed paper, thus discrediting Zak and Novoselov. Calment’s life exemplifies many of the features of lifestyle in the Blue Zones and covers all of the secrets for successful ageing. She had financial security, was relatively free from stress, experienced a varied and full life, had plenty of outdoor activities, was consistently curious throughout her life, had lots of friends and social engagement, ate good food and practised beneficial routines and rituals until her death. Had André-François Raffray known how her family history and lifestyle would contribute to healthy, longer living, he may well have declined the property deal in 1965, which cost him dearly! Most of us who read Calment’s story will surmise that her longevity was thanks to ‘great genes’ but there are a number of theories worth discussion. Early researchers concluded that the process of ageing was linked to fertility. In other words, they thought that mortality increases as fertility declines and all biology is dependent on this relationship. Although many species, like humans, do show mortality trajectories consistent with this theory, there are plenty of violations. In some species, such as the desert tortoise, mortality declines with age, while in others, such as the tiny freshwater organism known as the hydra, it remains constant. So fertility does not explain why all animals age. Moreover, and amazingly, the shapes of mortality trajectories are not strongly associated with the lifespan of species. In other words, both short-and long-lived species have increasing, decreasing or constant mortality rates.

Chapter 2: Why Do We Age?

For example, humans and other mammals are more likely to die with increasing age, while plants are highly variable. Longevity can be manipulated. Probably one of the greatest breakthroughs in the field so far is manipulation of genes and thus longevity and its plasticity, i.e., slowing down or speeding up ageing. We know, for instance, that manipulation of DNA repair systems in mice sometimes accelerates ageing. On the other hand, we can turn off a single gene, like growth hormone receptor gene, and significantly extend the life of a mouse. Much research has been invested in this very approach – switching genes ‘off and on’ – in order to reduce diseases and slow down the ageing process. To date, these studies have only been conducted in animals and are not as yet safe to conduct in humans. But there are other theories for why we age apart from genes. Knowing the various theories will help understanding of what we as individuals can do to slow down ageing and achieve a healthy lifespan close to that of the Blue Zone people. There are a number of explanations as to why, apart from genetics, cells age – and no one explanation clearly dominates. One theory is that an accumulation of toxins, free radicals and bad proteins builds up in cells, thus causing damage which eventually kills the cell. Another is that ageing is programmed, i.e., through an internal clock to live to a certain age. A more recent popular theory is that the immune system alters as we grow older, ‘attacking’ and eventually killing us.

We will briefly explore each possibility because they inform the recommendations for successful ageing in subsequent chapters. I have tried to simplify the explanation of the science and have kept it as brief and as straightforward as possible.

Chapter 2: Why Do We Age?

Let’s first start with genes because, in my experience, this is the theory that is most strongly embedded in popular belief. Genes are responsible for up to 30 per cent of how long we live for up to age 80 and play a much larger role in likelihood of longevity thereafter. Even very recently, I gently disabused a patient of his firm conviction that ‘genes are everything’ and that he had nothing to worry about because his father had died aged 94 and his mother, aged 87. Therefore, he, aged 68, assured me that although he smoked 20 cigarettes per day, was overweight and consistently enjoyed at least a half a bottle of wine daily, it would not make any difference to his health. After all, he said smiling, ‘I have great genes.’ His pronouncements are not entirely correct. Ageing is, only in part, determined by the genes we inherit. We have two copies of each gene – one inherited from each parent. Most genes are the same in all of us but a small number (less than 1 per cent) are slightly different between people. We have between 20,000 and 25,000 genes. Allelles are forms of the same gene with small differences in DNA. These small differences make up our unique physical features. ‘Twin research’ has taught us a lot about genes and ageing. Identical twins provide a ‘natural experiment’ because they have the same genes at birth and so are ‘genetically programmed’ to age in the same way – however, they do not do so! This is because life experiences and environmental factors including lifestyle behaviours (such as my patient’s smoking, drinking and diet) have a big effect on how fast or slowly we age and predominantly determine how long we live for. An early study of 2,872 Danish identical twin pairs compared the relative contribution of genetics and other ‘environmental’ factors. Born between 1870 and 1900, the genetic influences in the twins in this study were minimal up to late adult life but did get stronger after this. In other words, childhood experiences, social and economic circumstances, marital status, diets, sleep, smoking habits, alcohol intake, depression, stress and physical activity predominantly influenced ageing for the first numbers of decades, with genes only becoming more dominant in latter years. Other twin studies followed, confirming that genes contribute to only 20–30 per cent of the variation in survival up to 80 years and genetic factors play a much stronger role in long living beyond 80. The remaining 70–80 per cent of variation in survival up to age 80 is due to external or environmental factors. So, if my patient makes it to 80, then his hypothesis about his genes protecting him may prove correct. He is much more likely to succumb to problems from his lifestyle behaviours well before that. So genes play a dominant role in exceptional longevity – that is, reaching 100 or more.