My mother in-law is 85 years old and watches her diet carefully. She sees her physician at a Malaysian government clinic regularly. My wife takes care of her well-being like any daughter would do. She is the oldest among her siblings, who grew during the Japanese occupation in the Second World War. She also saw how the British rubber planters lived in her small town of Rantau, Negeri Sembilan, Malaysia. In the 1960’s she saw at every evening British rubber planters and their wives congregated at a club house in the centre of the town till the early hours. We hope she can live till 100 years.
We read an interesting article by Damian Whitworth in the Times London on September 30th on advances made in the area of ageing. He reported research works done by geneticist David Sinclair, who is a longevity expert who believes we will soon be able to boost our genes to defy the ageing process
He interviewed David Sinclair who is a professor at the Harvard Medical School, Cambridge, USA. He is a 50-year old and believes that the pioneering work he and other human biologists are doing could help him to live for another 80 years. He is an author of a book, Lifespan: Why We Age-and Why We Don’t Have.
The following is an extract of the interview.
David Sinclair, an expert on ageing, has some extremely eye-catching things to say about how long we might live and what that means for the future of our species. He would like to see the 22nd century. “That would mean making it to my 132nd year. To me, that is a remote chance, but not beyond the laws of biology or way off our current trajectory,” he writes in Lifespan, his new book about how medical science is changing our futures.
Jeanne Calment, who is believed to have lived longer than any other recorded person, died in France at the age of 122 in 1997. By the turn of the next century a 122-year-old will be thought of as having led a full life, but not a particularly long one, Sinclair says. Hitting 150 may not be out of reach. And then? “There is no biological law that says we must age.” We are, he says, about to “redefine what it means to be human, for this is not just the start of a revolution; it is the start of an evolution”.
Sinclair runs a laboratory at Harvard Medical School, where he is a professor in the department of genetics and a co-director of the Center for the Biological Mechanisms of Aging. He runs a sister laboratory at the University of New South Wales in Sydney, Australia, where he grew up. He made his name in the mid-2000s when he demonstrated that the natural chemical resveratrol mimicked calorie-restriction in yeast and made the cells live longer. In 2013 he made headlines with his work to stimulate longevity genes in mice so that the effects of ageing were reversed and old mice found new vitality.
I had been expecting, after reading his book with its bold claims, to encounter a grand figure, but Sinclair is relaxed and understated in conversation. Clearly, though, he is not shy of making the sorts of assertions of which many scientists are usually wary.
“Well, the world, in my view, is sleeping on the job,” he says. “I’ve just spent the last two years seeing results in my laboratory and in my colleagues’ laboratories that I thought I’d never see; finding that there’s a back-up hard drive of youthfulness. In 50 years’ time it’s really impossible to imagine the kinds of advances that’ll be possible.”
Sinclair works on sirtuins, which have been dubbed “longevity genes”. There are seven sirtuins in mammals, made by almost every cell in the body. They control health, fitness and survival, and require a molecule called nicotinamide adenine dinucleotide (NAD). The diminishment of NAD as we age is understood to be a primary reason why our bodies develop diseases when we are older. Longevity genes can be activated by exercise, intermittent fasting, low-protein diets and exposure to cold temperatures, Sinclair says. “But over time, diet and exercise are not sufficient. We need more than that.”
That’s where science comes in. NAD increases the activity of all seven sirtuins. Sinclair’s research has found that old mice that were fed nicotinamide mononucleotide (NMN), an NAD-boosting molecule, suddenly started running ultra-marathons.
NAD boosters extend the lives of mice. There are indications that NAD boosters may restore the fertility of old mice, and positive signs from another trial in mares. The implications are enormous if women can look forward to extending their fertility window. Sinclair is careful to say that what happens in mice might not necessarily happen in humans, but “if that works in women the way it’s working in mice and in horses, then women can start to think differently about their lives”.
Sinclair predicts that another key path to prolonging youth will be cellular reprogramming, in which ageing cells are reset — like DVDs that have had their scratches removed and lost information restored. Shinya Yamanaka won the Nobel prize in physiology or medicine in 2012 for discovering that a set of genes could turn adult cells into pluripotent stem cells, which can become any other cell type. Sinclair’s team is working on developing this “switch” to reset cells in the petri dish and then, he hopes, in the body. He envisages a day when we could be administered a specially engineered virus carrying reprogramming genes that are switched on by an antibiotic. A person in their forties would feel 35 again. Then 30 and 25.
“Theoretically you could reset tissue or the entire body every ten years,” he says. “We don’t know how many times we can reset, but that’s one of the exciting areas of the field.” The very significant downside could be that the process causes cancers. “But I’ve been pleasantly surprised that we reprogrammed mice with a virus last year and those mice are still fine — no evidence of any downsides.”
A third part of the approach that Sinclair outlines in his “information theory of ageing” is attacking senescent, or “zombie”, cells. These are cells that have stopped dividing, but aren’t dead. They can cause inflammation, and while restoring them would be a tall order, a class of drugs — senolytics — are being developed to kill them, which should aid rejuvenation, according to Sinclair.
He is not a medical doctor, so he won’t give advice, but he does share details of how his knowledge of the frontline research on ageing shapes his daily life. His aim is to walk a lot of steps each day, take the stairs, and lift weights and run at the weekend at the gym, where he also takes a sauna and dunks in an icy pool. He tries to stay cool during the day and when sleeping.
His diet is plant-heavy, but he’ll eat meat after he has done a workout. He tries to miss one meal a day or have one very small one. His sugar, bread and pasta intake is low, and he gave up desserts a decade ago. Every few months he has his blood analysed for biomarkers and makes adjustments to his diet and exercise if anything shows up. He doesn’t smoke and avoids microwaved plastic, excessive exposure to UV, x-rays and CAT scans.
As well as daily doses of vitamin D, vitamin K and aspirin, he takes a “triple combo” of anti-ageing supplements. NMN is made by our cells and found in avocados, broccoli and cabbage. It increases the levels of NAD in the body, but you’d need to eat an awful lot of avocado toast to achieve the same effect as the gram that Sinclair takes at breakfast.
Metformin, a derivative of French lilac, is used as a diabetes medication, but shows signs of prolonging vitality. In studies it has been seen to increase the lifespan of mice, and among human users it apparently reduced the likelihood of dementia, cardiovascular disease, cancer, frailty and depression.
Sinclair takes a gram of that too, along with a gram of resveratrol in his homemade yoghurt. Resveratrol, which is found in red wine, protects against many diseases and extended the lifespan of yeast cells and fruit flies. Is this good news for boozers? Not really. The dose Sinclair takes “would be the equivalent of about 500 glasses of wine for breakfast”. He drinks the occasional glass of red wine.
Sinclair was a co-founder of a company that was set up to test resveratrol, which he promoted as “close to miraculous”. The company was sold to GlaxoSmithKline, which allegedly ended the research because the results were underwhelming. Sinclair, who made a reported $8 million from the sale, says that he would love to “reinvigorate” the programme.
His sprightly 80-year-old father is on the same regimen as Sinclair, who has even put the three family dogs on NMN. He shows me the ring he wears that monitors his heart rate, body temperature and movements. This is just the beginning of the way in which we will monitor ourselves as companies read our genomes and monitor our glucose, the oxygen levels in our blood, vitamin balance and hormones, and diagnose neurodegenerative diseases from subtle changes in our movement long before symptoms are noticeable.
Is there not a danger that all this data will result in losing some of the fun of life?
“You can combine fun and fact,” Sinclair says. “It’s not for everybody. A third of the population, at a rough guess, is really interested in their long-term health and would love to have some additional incentives.”
He has done some “conservative” maths about what scientific developments will achieve over the next 50 years. DNA monitoring will soon be alerting us to diseases long before they become serious, allowing us to start treating cancer and other conditions earlier — that could give us an extra ten years of life.
Eating fewer calories and fewer animals, doing more exercise and getting cold enough to boost the development of “healthy” brown fat, which research suggests correlates with longevity in rodents, could add another five years. Molecular treatment to turbo-charge our longevity genes could add another eight.
Then we could reset our epigenome — the control systems and cellular structures that govern which genes should be turned on and off — with molecules or genetic modification, destroy senescent cells with drugs or vaccinations and replace worn-out organs with those from genetically altered farm animals or 3D printers. All this might add another decade.
That’s 33 years added to the roughly 81-year life expectancy of a person in the UK. And we won’t be decrepit old people; we will be full of vitality.
Yet will a life expectancy of 114 be just for the rich? Sinclair warns that we stand on the brink of a world in which the wealthy could ensure that their children, or even their pets, live far longer than the children of those living in poverty.
“Some of these medicines might be very expensive initially, though they’ll come down in price.”
And don’t those rejuvenated people eventually become incapacitated? “They will,” he says, but the research suggests they’ll die quicker. The expensive people are the ones who are sick for a long time.
Sinclair is unusually energetic, and you can imagine him carrying that into deep old age. But what if millions and millions of the rest of us are quite happy to be ancient and fit, but just want to sit around? “We can’t retire at 65 and live another 65 years,” he says. “It’s just not tenable. It’s not fair to the younger people. There will have to be adjustments.”
We’d have to address our levels of consumption to make living on our planet sustainable and to avoid the environmental crisis becoming further exacerbated by a growing, ageing population. Our social security systems can’t support half a life of retirement. “We are flying blind into one of the most economically destabilising events in the history of the world,” Sinclair says. He doesn’t have all the solutions.
Critics suggest that there is a temptation for those in the highly lucrative field of longevity research to over-hype what is possible, although Sinclair tells me that “income to my family from my inventions is put back into medical research and innovation”.
Jeffrey Flier, a former dean of Harvard Medical School, this year criticised the publicity on longevity studies. “If you say you’re a terrific scientist and you have a treatment for ageing, it gets a lot of attention,” he said on the website Kaiser Health News. “There is financial incentive and inducement to overpromise before all the research is in.”
What Sinclair says he wants more than anything is for everyone to expect to meet their great-great-grandchildren. By knowing future generations, he argues, we will feel more accountable for our actions today. “It will compel us to confront the challenges that we currently push down the road,” he says. “To invest in research that won’t just benefit us now, but people 100 years from now. To worry about the planet’s ecosystems and climate 200 years from now.”
Note:
Lifespan: Why We Age — and Why We Don’t Have To by David Sinclair is published by Harper Thorsons.