People are living longer. While this is to be celebrated, old age brings with it a host of age related diseases that are putting a strain on global health services. Is there a way to combat this, to ensure that people not only live longer, but live healthy longer? PhD student Adam Field (joint with the Cancer Research UK Beatson Institute) studies the molecular mechanisms underlying cancer susceptibility in relation to biological ageing. Here, Adam discusses the broader field of biogerontology, and what we could learn from animals that are seemingly better at ageing than us.
Forever Young
Learning to Stay Healthy to 100
We humans are very good at getting old. In fact, we are the longest lived land mammal alive today, routinely living 80-90 years and frequently more than a century. But it has not always been this way. Our lives have been getting longer and longer over the past century largely thanks to modern medicine, which has drastically reduced infant mortality and a whole host of infectious diseases. Unfortunately, as with so many things, we have become a victim of our own success.
The world as a whole is getting older at an impressive rate. As a result, we’re looking at an incoming tidal wave of elderly individuals. This trend has been referred to as the ‘silver tsunami’ and it’s becoming increasingly apparent that we need to learn how to ride the wave.
Our health services and economy are already feeling the effects. More of us in old age means a larger proportion of the population suffering from age related disease, such as cancers and dementia, with fewer working age individuals to support them. If we are to enhance the well-being of our older population and ease the strain on our society, we will need to learn how to remain healthier for longer. Luckily, some animal species are better at this than we are. My job is to find out what we can learn from them.
Golden Oldies
There are a great many animal species out there that leave us in the dust when it comes to ageing. We may be able to push 100 years of age, but recent discoveries have suggested that the Greenland shark may live more than 400 years. Atlantic clams show similar record-breaking longevity, living almost half a millennium. A small pond-dwelling animal called the freshwater hydra doesn’t bother ageing at all. All evidence seems to suggest these diminutive creatures never get old. At least, not in a way we’re familiar with.
The revelation that ageing is not universal, with some animals living for hours and others for centuries, inspired my field of biology: biogerontology. A mouthful that is best described as simply ‘ageing biology’. Scientists in this field have worked hard to find out what exactly allows some animals to live so much longer than others. More importantly, how do they remain disease free for so long? Answering this question may allow us to apply such knowledge to humans, delaying our age related decline.
Greenland shark. Image by NOAA Okeanos Explorer Program (Public Domain), via Wikimedia Commons. Ming, the ocean quahog clam that lived to 507. Image by AD Wanamaker Jr et al. (CC BY 3.0), via Wikimedia Commons. The ‘Immortal” Turritopsis dohrnii medusa. Image by Bachware (CC BY-SA 4.0), via Wikimedia Commons.
Ageing Under the Microscope
The first steps towards understanding the molecular biology of long-life came from the lab of Cynthia Kenyon. Experimenting on nematode worms, she demonstrated that by simply deleting a single gene, she could double the worms’ lifespans. Further, experiments in flies, and more recently mice, have shown that by making targeted alterations to certain biological programs we can make animals live healthier, longer lives.
At the forefront of this research are the dwarf mice. Discoveries made in simpler organisms suggested that by lowering the expression of genes involved in growth and energy utilisation, whilst increasing expression of genes involved in stress resistance, may have beneficial effects. The Ames dwarf mouse is one such example. This tiny mouse, half the size of its ‘normal’ counterparts, trades it’s size for being healthier and living almost 50% longer. These ‘super mice’ result from a lack of growth hormone circulating in their blood. Therefore, it seems that high levels of growth hormone may not be conducive to a long, healthy life.
Graph showing the increased survival rates of Ames dwarf mice compared to their ‘normal’ counterparts. Image by Holly Brown.
Hunting for the Elixir of Youth
All this work has profoundly altered how we view our own lives and what happens to us as we move into our twilight years. The discovery that we can slow down ageing and reduce disease incidence with age in lab animals has opened up many research possibilities. Can we take inspiration from the mechanisms seen in creatures like dwarf mice or Greenland sharks, create drugs using this knowledge, and use them to treat age related disease?
Rapamycin is a chemical isolated from a strain of bacteria native to the isle of Rapa Nui, or Easter Island as it is better known. Initially, the drug was used as an antibiotic and was later applied to preventing organ rejection in transplant patients. But rapamycins’ biggest trick was yet to come. In the early nineties it was discovered that rapamycin delays ageing, at least in mice, flies and other laboratory animals. It prevents a huge host of age related diseases, including cancer. The best part is that this drug is already used safely in humans. It may represent our best candidate for a pill that can ensure a longer, healthier life for us all. My research focuses on understanding how rapamycin affects our cells so we can use this knowledge to better human health late in life. We have already shown that rapamycin can prevent or even reverse errors that accumulate with age in our epigenetic code, the system which regulates and controls our DNA.
Treating Ageing
Currently, ageing is not considered a viable target for therapy as it is not considered a disease. However, as the population ages and the diseases this brings reap their toll, medical science will need new ways to cope. The first clinical trials testing whether drugs can slow ageing in humans will soon be under way in the form of the TAME (Targeting Aging with MEtformin) trial, using the diabetes drug metformin in a cohort of healthy volunteers. The objective of the study is to see if the individuals on metformin develop less age related disease than their counterparts, a first step towards preventing age related disease by pre-emptively targeting ageing itself. A future where treatment begins before we even get a disease may soon be on its way. As the old adage goes, prevention is almost always better than cure, and preventing ageing may be our best hope for healthy future generations.
Ames dwarf mouse (right) compared to its ‘normal’ counterpart (left). Image by Teresa Valencak.
Adam is a keen science communicator; you can find his writing in places like F1000, The GIST, and The Epigenetics Literacy Project.