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Autumn 2017

Will I ever live forever?

Copyright: Aaron Jacobs on Flickr by CC 2.0

In the 1800s, the average lifespan was around 40 years; today it has almost doubled.

We ask some BBSRC researchers working at the frontiers of bioscience if living forever could be a possibility. From cellular metabolism to ageing and cognition they are working on frontier bisocience projects that will help us understand whether people will ever live significantly longer and healthier lives than we do now.

Copyright: Babraham Institute
Professor Wolf Reik is based at the Babraham Institute. Copyright: Babraham Institute

How can epigenetics help longevity?

Professor Wolf Reik, based at The Babraham Institute, heads a world-leading research group that looks at epigenetics - the way molecular markers can turn genes on and off in cells - which can affect gene expression and the destiny of cells, especially the stem cells that are the source of adult tissues. Understanding how stem cells develop is critical to increasing longevity and healthspan.

“We are working on an epigenetic clock which predicts chronological and biological age, so that we can understand better what factors accelerate or slow down ageing”, says Reik. “However such a clock is only known in humans so far, hence experimental opportunities have been limited.”

His group are working towards unravelling such a clock in the mouse which he says will open many exciting research avenues in terms of changing the ticking rate and age-reprogramming.

But Reik doubts whether humans will achieve significantly longer longevity. “Although progress is being made in understanding the ageing process and underlying mechanisms, there isn’t yet a unifying principle that you could think of tinkering with in humans.”

Could our muscles work forever?

Dr Carrie Ferguson, is a lecturer in exercise physiology based at the University of Leeds, and works on a collaborative BBSRC-funded project with Dr Harry Rossiter (University of Leeds) and Professor Graham Kemp (University of Liverpool) to find out how ageing affects muscle function.

Copyright: BBSRC
Dr Carrie Ferguson, pictured outside an MRI Scanner that is used to measure exercise in action on old and young participants. Copyright: BBSRC

If we want to understand whether we will ever live forever, then we will need to understand how the human body can maintain its ability to respond to physical activity and exercise as we age. Ferguson says that aerobic capacity (a measure of fitness) is the strongest predictor of mortality and morbidity that we have.

“Our BBSRC research aims to provide a better understanding of the intramuscular limits to aerobic capacity and exercise tolerance,” she says. “With a better knowledge of the limits to exercise tolerance across the lifespan, the next steps are to understand how best to intervene to overcome limitations to exercise tolerance across the lifespan to allow for healthier and happier independent living.”

So, does the team think that exercise is the key to longevity? “No. We do not believe that the human genome is designed for this type of longevity, whatever the methods used to promote a youthful physiology,” says Ferguson. “It seems likely that around about 120 years is the best that can be expected. The ideal would be to maintain optimal health and function for as much of this 120 years lifespan as possible - this is encompassed in the notion of the ‘healthspan’ as opposed to the lifespan.”

Will my immune system still protect me in very old age?

Professor Neil Mabbott is based at The Roslin Institute at The University of Edinburgh. He investigates host-pathogen interactions in the mucosal immune system, including how the immune system functions with increasing age.

Copyright: Norrie Russell, The Roslin Institute, University of Edinburgh
Professor Neil Mabbott from The Roslin Institute at The University of Edinburgh. Copyright: Norrie Russell, The Roslin Institute, The University of Edinburgh

It has been known for some time that as we age our immune systems become less effective, and we are much more susceptible to microbial infections, as well as cancer and inflammatory diseases, than when we were younger.

“We call this process immunosenescence,” says Mabbott. “We are trying to understand the factors which cause the immune system to become less efficient as we get older.”

Mabbott’s group have been using BBSRC funding to look at how ageing affects the organs of our immune system, and the how the ageing gut responds to pathogens, including prions. They have found that ageing dramatically affects the structure and function of certain immune system components.

“The aging immune system can less easily recognise foreign particles (antigens) and pathogens and mount an immune response against them,” Mabbott explains. “If we can identify why this happens we may be able to develop a novel treatment to help repair or reverse these changes and improve the immune systems of the elderly.”

So how does Mabbott rate our chances of living forever? “I think the ability of humans to live longer than 200 years or so is probably not biologically achievable. Of course, aging research should help us to find novel ways to ensure we can live healthier and active lives as we age.”

How healthy will I be in old age?

Professor Alison Woollard presented the Royal Institution Christmas Lectures in 2013. Based at the University of Oxford, she is now using BBSRC funding to develop novel approaches that determines healthspan.

Copyright: Paul Wilkinson
Professor Alison Woollard presented the Royal Institution Christmas lectures in 2013. Copyright: Paul Wilkinson

The last 100 years have seen almost a doubling in lifespan in the UK due to medicines, nutrition and social care. Can we match that over the next century? “I suspect improvements in the traditional approaches to extending life will probably slow down - the ‘low hanging fruit’ may have been picked,” says Woollard. “If we can understand why and how we age - in the biological rather than chronological sense - then it may be possible to treat ‘ageing’ itself, targeting several diseases of ageing at once.”

Woollard works with much-studied nematode worm C. elegans that shares many of its genes with people and so also shows recognisable signs of biological ageing. She explains that mutating either the wrn-1 gene (equivalent seen in people as Werner syndrome) or the p53 gene results in shortened worm lifespan. “Yet if worms carry both of these detrimental mutations, surprisingly they live even longer than a normal worm - and this increase in lifespan is accompanied by an increase in healthspan.”

These genes produce proteins in people, as well as in the worms, that could be targets for intervention through lifestyle changes or drugs. “We are investigating the mechanisms behind this novel phenomenon - which we call synthetic superviability - and whether there are other combinations of genes and environmental factors that can also be harnessed to improve the health span of worms, and hopefully that of humans.”

Won’t my bones be brittle and break in old age?

Professor Richard Oreffo, based at the University of Southampton and Director of the Centre for Human Development, has developed a way to create hip replacements using a patient’s own stem cells.

Copyright: University of Southampton
Professor Richard Oreffo has used a patient’s own stem cells for hip replacements. Copyright: University of Southampton

Key to additional years of life accompanied by years of good health is the ability to repair damaged tissue, such as bone. “We are harnessing stem cells including a patient’s own bone stem cells with appropriate scaffolds and have delivered molecular growth factors (messenger RNA, microRNA, protein cues etc.) to aid functional bone and cartilage repair,” Oreffo explains.

Reprogramming cells to create specific cell and tissue types is a powerful tool to regenerate and repair body parts. Add that to the ability to harness additive manufacturing techniques like 3D printing so that a patient’s own stem-cell derived cells can sit on bespoke scaffolds - think a hip joint shaped matrix - and we have the ability to make tissues. But not just tissue in a flat petri dish, but bone-muscle-tendon complexes, or bone-cartilage constructs.

“This will allow us to repair damaged and diseased tissue and create bespoke and tailored tissues that will dramatically improve quality and function and improve patient outcomes and, ultimately, a patient’s quality of life,” says Oreffo. But he adds that it’s unlikely we’ll see a significant extension in lifespan in the next 50 years. “Rather, research will offer us the opportunity for a healthier and longer life, in contrast to current advancements in longevity often accompanied by frailty and disability.”

Life and death in numbers

  • From 2010 to 2050 there will be a projected 350% increase in the number of people over 85
  • Some animals, planarian worms and jellyfish like Hydra, avoid the ageing process altogether, demonstrating that it is not inevitable for animals to age. These animals are also capable of amazing feats of regeneration, able to regenerate their entire body parts from small starting fragments. This ability to regenerate is fuelled by the presence of many stem cells in adult animals
  • The accuracy of the human epigenetic clock - a way of estimating the biological age of a tissue, organ or organism by measuring DNA methylation levels in a specified set of genomic positions - is within +/- 3.6 years in humans
  • One in two women and one in five men over the age of 50 will experience an osteoporotic fracture in the UK
  • Some octogenarian athletes are able to maintain aerobic capacity close to the median of those 40 years younger. In one case study, a man was able to increase aerobic capacity by 13% through exercise training between the ages of 101 and 103.

Header image copyright: Aaron Jacobs on Flickr by CC 2.0


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