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Does anyone my age have any chance of living for centuries? Will younger generations have a chance? - Adam Barclay, 44, Newcastle.
One century? Yes, a decent chance. We might in theory be able to live for centuries. This is a dream that many are working towards - but we aren’t there yet.
The subject of living longer, and more importantly, healthier lives is now a serious, mainstream endeavour in biology and medical science.
Molecular biologists, geneticists, and nutritional scientists are reaching for the ultimate goal of delaying onset of age-related conditions, which would reduce the incidence of nearly every non-communicable disease ageing brings.
Although reduced disease burden is the public health goal that motivates governments and the medical science community to pursue ageing research, it is living longer - finding the elixir of youth, seeking immortality - that captures the public imagination.
With the exception of wars, famine, or major economic dislocation, human lifespan has been steadily increasing around the world for the past century. Life expectancy in Australia is around 83 years, the fourth greatest in the world. These gains are largely due to improved access to and quality of health care. We are yet to see the impact of therapies specifically targeted to treat ageing, which could turbo-charge this increase in life expectancy.
What researchers are working on
Most of the anti-ageing or “geroprotective” compounds under development work by mimicking the effects of calorie restriction or physical exercise. Lifelong calorie restriction, reducing calorie intakes by around 30%, is one of the strongest interventions known for extending lifespan.
For the past two decades, research into ageing has sought to determine which genes and molecular pathways are turned on and off by eating less and exercising more. This has resulted in the discovery of a number of pathways (called the sirtuins, insulin/IGF-I signalling, mTOR, and AMPK) that can be manipulated in animals to extend lifespan. An anti-diabetic drug called metformin activates one of these, and is being trialled to improve health in old age.
Another way to extend lifespan might be to remove so-called “senescent”, or old and damaged cells, which cause disease. But here’s the thing - those pathways extend lifespan by only up to 30%, which on a “normal” human lifespan of 83 years, takes us to merely one century.
While increasing life expectancy to over a century would be an astounding achievement, this is nowhere near the centuries that many people dream of. To achieve that, the biology of ageing will have to move beyond mimicking calorie restriction, tinkering with metabolism, and trimming away old cells.from www.shutterstock.com
Possible future directions
Instead, we might look to nature for inspiration. The jellyfish Hydra has no discernable biological ageing, and is functionally immortal, most likely due to a high content of stem cells that can replenish the adult body. Another species, Turritopsis dohrnii, the “immortal jellyfish”, can reverse back from its adult body into its juvenile state, as a polyp growing on a rock, and then grow back into an adult, and repeat that cycle to achieve near immortality.
So how could we imitate the immortal jellyfish? Well, we could reprogram our “epigenomes” - which is the arrangement that keeps different parts of our DNA code turned on and off. Excitingly, we already know how to do this. There are just four genes, called “Yamanaka factors”, which rejuvenate adult cells back into embryonic stem cells - like Benjamin Button, this would mean turning our cells from aged adults back to those of a developing baby.
In theory, turning these factors on for the right amount of time in the right places could rejuvenate our bodies back into those of young people - at which point, in theory, we might be able to live for centuries.
The trick will be figuring out when, where, how much and for how long to turn these Yamanaka factors on. Too much, and our organs could turn into a mass of undifferentiated embryonic stem cells, which could grow back into the wrong tissue type. Too little, and there would be no effect. Getting the dosage just right could be very powerful. Testing for the first time in humans would be risky.
It’s worth remembering that extending lifespan alone is not the same as extending quality of life or healthy years. Advancement of lifespan should not occur by delaying death following long periods of sickness. Instead, shortening the amount of time people are unwell should be the ultimate goal.
At some point prior to death, everyone crosses the threshold of being independent, healthy and active, to becoming dependent, sick and immobile. The duration spent below this threshold is unique to the individual, but everyone agrees this time should be minimal in comparison to the person’s healthy years.
Lifestyle changes, and advances in technology and medicine, aim to maximise the proportion of time spent living life to the fullest and delaying the (unavoidable) onset of age-related conditions. But living for centuries remains a dream – for now.
Lindsay Wu is a founder, director and shareholder in Jumpstart Fertility and Life Biosciences. He is also a shareholder in Continuum Biosciences, Senolytic Therapeutics, EdenRoc Sciences, and Intravital. His lab at UNSW Sydney receive funding from the National Health and Medical Research Council (NHMRC) of Australia and Jumpstart Fertility, and has in the past received funding from Cancer Institute NSW and MetroBiotech NSW. His salary at UNSW Sydney is supported by an RD Wright Biomedical Fellowship from the NHMRC.
Stefanie Mikolaizak works at Robert Bosch Krankenhaus (Hospital) in Germany. RBMF is the medical research department associated with the hospital of the German charity foundation “Robert Bosch Stiftung”. She is currently coordinating the German clinical site of a large multi-centre intervention trial (PreventIT). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 689238.
Authors: Lindsay Wu, NHMRC Senior Lecturer, School of Medical Sciences, UNSW