Live long and prosper: lessons from super-centenarians
The oldest person alive at time of writing is Kane Tanaka, who celebrated her 119th birthday on 2 January 2022. [Edit 27 April, 2022]: Kane Tanaka died on 18 April 2022. According to a statement from Guinness World Records, Tanaka had been "hospitalized and discharged repeatedly" in recent weeks but remained in good spirits. Guinness has yet to name the new world recordholder, but experts had previously identified Lucile Randon, a French nun also known as Sister André, as the world's second-oldest person. She turned 118 in February.
Growing up in a small town on Japan’s southern island of Kyushu, Kane married at 19, gave birth to two sons and two daughters, adopted one more, and together with her husband managed the family’s small grocery store, that specialised in udon noodles and shiruko azuki bean pudding.
Surviving World War II, as well as surgery for pancreatic cancer in 1948, Mrs Tanaka converted to Christianity under the influence of US military pastors and continued to enjoy a peaceful married life until her husband died in 1993 aged 90. She moved into a nursing home in Fukuoka City in 2018, and despite recurring bowel cancer, and a reported fondness for cola and chocolate, [has] enjoyed generally good health.
Her hobbies include[d] calligraphy, maths puzzles, board games and increasingly shorter walks. She recently said she would be happy to carry on living, crediting her longevity to her faith, family, sleep, hope, good food and arithmetic. She was invited to carry the torch for the Tokyo Olympic Games in 2021, but pulled out due to concerns over Covid-19.
Mrs Tanaka is a statistical outlier, but by no means unique; there are now an estimated 500 ‘supercentenarians’ over 110 in the world. Most of these are women, and many are Japanese. Japan’s long life expectancy is often attributed to a varied low-carb traditional diet, and habits of frugality and hygiene, especially among the older generations. The southernmost island of Okinawa has nearly double the number of centenarians as the national average, which may be due to a diet rich in fish and vegetables, and lifestyle factors such as physical activity, low stress and caring communities that support older people.
100 not out: greetings from the Queen
The United Nations estimates the number of centenarians– people over 100 years old - in the world has quadrupled from around 150,000 in the year 2000 to 575,000 in 2020. This rapid increase in just two decades is a result of population growth as well as improved health and medical care in later life.
Some nations enjoy longer lives than others. Japan and Hong Kong have the highest average life expectancy at around 82 for men and 88 for women, and by far the highest proportion of centenarians – around 68 per 100,000, compared to South Korea at 43, with France, Germany, Canada and the USA around 30.
Japanese centenarians receive a silver cup and a certificate from the Prime Minister on Respect for the Aged Day, the third Monday in September. US centenarians receive a letter from the President on their 100th birthday. In the UK, the Queen sends a greetings card (previously a telegram), reading: "I am so pleased to know that you are celebrating your one-hundredth birthday, I send my congratulations and best wishes to you on such a special occasion".
Her Majesty is currently 95, and in good health, although she is limiting her public duties, especially since the death of her beloved husband Prince Philip a year ago at the age of 99. If he had lived just four months longer, he would have hit his century, so narrowly missed out on getting his own greetings card from the missus. We hope she will be able to send one to herself in 2027.
Some people worry that longer life may merely mean more years of misery, disease and disability, and that they may become a burden on their family and carers. However, the evidence seems to point the other way. Centenarians tend to stay healthy well into their nineties, and in supercentenarians, in their 100s.
The mystery of Mme Jeanne Calment
In 1942, a prosperous draper in the city of Arles named Fernand Calment died at the age of 73. His widow Jeanne, then 68, carried on living in their apartments above the family store, although ‘carried on’ living is an understatement – she continued in genteel good health for another half century. She had never had to work, and well into later life enjoyed walking, cycling, tennis, swimming, fencing, playing the piano and socialising, known for her waspish sense of humour.
At the age of 100, she fell off her bike and broke her leg, but was walking again within weeks. Shortly before her 110th birthday, the cold winter of 1985 froze the water pipes in her flat, where she refused to use heating, and gave her mild frostbite. She decided to move to the Maison du Lac nursing home, where she kept up a strict daily routine. This included morning prayers, coffee, exercises to music, fruit salads, chocolate, one cigarette and a small glass of wine, chatting, crosswords, more music and bed at 10pm.
She attributed her longevity to God, olive oil, exercise and living up to her name by keeping calm. By now, she attracting the attention of medical researchers and the media. At 114 years old, she claimed that she had never taken any medicine, apart from aspirin for migraines, and had somehow managed to avoid illness. In 1990, she fell and fractured her femur. Following surgery, she could no longer walk and used a wheelchair.
She finally quit smoking at 117, but refused a routine cataracts operation to restore her eyesight. At the age of 118, neurophysiological tests and a CT scan showed her verbal memory and language fluency compared well with people 30 years younger, and she showed no signs of neurological disease, depressive symptoms or other illness. She died of ‘unspecified causes’ on 4 August 1997, at the age of 122, and reportedly remained cheerful and mentally sharp until the very end.
In 2018, a Russian mathematician Nikolay Zak caused uproar by claiming that it was not Jeanne Calment who died in 1997, but her daughter, Yvonne, who according to official records had died of tuberculosis aged 36 in 1934. According to Zak and his supporters, it was in fact Jeanne who died then with Yvonne assuming her identity, possibly as a tax dodge. This would naturally explains how she seemed 30 years younger than her true age, but would require an unlikely degree of deception by the great and good of Arles.
The controversy is well covered in a feature by journalist Phil Hoad in The Guardian. Meanwhile, Mme Calment remains the oldest fully documented person ever, and the only person to live beyond 120, though we can expect her record to fall within the next few years, if not to Mrs Tanaka, then to another Japanese supercentenarian.
It is encouraging that so many more people around the world are now living longer and healthier lives, but has medical science really succeeded in significantly extending the maximum human lifespan?
Ancient ancients show it ain’t necessarily so
A look back at the history of human longevity suggests not, or at least not yet. Although the number of centenarians is on the rise, that doesn’t mean maximum lifespans today are much longer than they have been over the past few millennia.
According to Genesis, Noah was 600 years old when the flood came, and lived another 350 years afterwards, despite being an alcoholic.
While we can dismiss the 900+ lifespans claimed for Adam, Noah, Methuselah and other biblical patriarchs, the three score years and ten of the Torah, or in Psalm 90 "The years of our life are seventy, or even by reason of strength eighty", seem not unreasonable, and are echoed by sources from Greece, Rome and elsewhere in the ancient world.
Ancient accounts of individual centenarians include Cicero's wife Terentia, reported by Pliny the Elder to have lived to 104. Adad-guppi, mother of Nabonidus the last Babylonian Emperor lived c. 648-544 BC (also 104 years) according to inscriptions on funeral steles. Several ancient Greek philosophers including Democritus are reported to have lived beyond the age of 90 or even 100.
Though reliable demographic data are scarce, there is evidence that lives became nastier, more brutish and shorter in medieval Europe. It is certain that until the 20th Century, both birth rates and rates of infant and child mortality were much higher, as were death from violence and infectious disease in adulthood. Despite this, people who survived these had a reasonable chance of living to a ripe old age, at least in society’s upper strata.
So most of the dramatic increase in average life expectancy over the past century is thanks to improvements in health and hygiene that have cut premature deaths, boosting the average still further. So can we expect future generations to live much longer than Mrs Tanaka and Mme Calment?
The prospects for longer, healthier lives
In recent years, there have been great advances in the field of bio-gerontology, the study of ageing processes in organisms ranging from roundworms to rodents to rockfish, and their implications for human health. While ageing is a multidimensional process, involving complex genomic and cellular changes, there are some simple things most of us can do to improve our chances of living longer. There are also some more radical things that scientific progress might make possible in the near future.
The simple things are not surprising. Good diet, eating well and not too much, is vital. Many studies in animals and humans show the benefits of dietary restriction. Laboratory mice kept on restricted diets can live several times longer than their free-eating siblings, but that doesn’t mean near-starvation is good for humans. However, over-eating and obesity are associated with many of the diseases of ageing, while intermittent fasting, as practiced in many traditional cultures has been shown to slow cellular ageing and have other health benefits.
Physical activity naturally helps burn fat, but also seems to have other positive effects on metabolism and even on the genome. Brisk walking is associated with longer telomeres, the sequences on the end of DNA strands that protects them from damage, and exposure to high or low temperatures such as cold-water swimming seems to affect epigenetic factors. Good sleep, gut health, oral hygiene and low blood pressure are also clearly correlated with health and to some extent with longevity.
While there are no drugs yet demonstrated to extend lifespan, there are promising developments in drugs that can simulate the effects of dietary restriction, and in natural compounds that can stimulate protective cellular processes.
Genomic revelations and tech revolutions
Studies of centenarians suggest that luck, in the form of genetics, plays an even greater role. The New England Centenarian Study, running since 1995 with a cohort of several hundred people over 100, has published several key papers that found that exceptional longevity runs strongly in families, and the degree of genetic influence upon survival increases in older ages. So if your parents survive into their nineties, it’s a very good sign for you!
This probably involves many genetic variants with individually modest effects, that cumulatively slow ageing and decrease risk for ageing-related diseases such as heart disease, stroke, cancer, diabetes and Alzheimer’s. However there are two genes that seem to be most strongly associated with longevity: APOE and FOXO3. APOE codes for a protein involved in cholesterol transport – the APOE2 variant appears to be protective against the diseases of ageing. FOXO3A, which occurs more frequently in centenarians, seems to simulate the beneficial effects of dietary restriction on cellular ageing.
A team led by Nir Barzilai at the Albert Einstein College of Medicine discovered three other rare gene combinations in many centenarians in New York. One raises HDL cholesterol to at least double average levels, another reduces thyroid activity, and a third restricts human growth hormone. They also identified a rare variant of the SIRT6 gene that increases DNA repair in human cells, among centenarians of Ashkenazi Jewish ancestry,
These genetic factors seem to counteract the effect of less than healthy lifestyles. The stereotype of a grandpa who lived to 100 despite smoking 60 cigarettes a day may be exaggerated, but many people in the New England Centenarian Study enjoyed a century free of cancer or heart disease despite smoking and drinking. Surveys of Okinawan supercentenarians show over half had a history of smoking and one-third were regular alcohol drinkers.
As some of the more promising drugs and gene treatments currently in development are introduced over the next two decades, it will extend lives long enough for more radical technological advances to be introduced. These include epigenetic reprogramming using stem cells. Australian geneticist David Sinclair at Harvard is leading researcher in this area, and has shown that partial reprogramming can dramatically reverse age-related phenotypes in the eye, muscle and other tissues in cultured mammalian cells and rodent models.
These results have naturally sparked interest among investors including Amazon’s Jeff Bezos, and several start-ups are raising tens of millions of dollars and racing to develop the technology. With such billionaire backing, advances in genomics and the vast computing power now available, we can only expect the pace of discovery to accelerate.
New discoveries are being made every year, and I hope to explore some of these in future posts, including some interviews with scientists working at the cutting edge of bio-gerontology.
Some leading advocates of anti-ageing science believe that human have the potential for far longer lifespans. Aubrey de Grey, founder of the SENS institute and Methuselah Foundation, famously claimed that the first human to live 1,000 years is probably already alive. It seems a bit of a leap, but there are reasons for this wild-seeming optimism.
Being human…
We know we are all going to die. But we do not yet know what the biological limits to ageing might be. Some organisms, such as the immortal jellyfish seem to be able to reverse ageing and reset their genomic clocks. Like Tolkein’s elves, although they may die, they do not grow old.
If immortality is biologically possible, it is a realistic prospect, given time and technology. Hence the optimism of de Grey and ‘rationalist’ thinkers like Open Philanthropy founder Holden Karnofsky who predict that sometime this century, we may well develop super-powerful artificial intelligence that will be able to deploy as yet unknown technology to cure all human diseases, including ageing.
There is a lot of exciting work to do before then, and I hope to share some of it in this blog, so please do comment and suggest topics for future posts.