By Holly Giles | Deputy Editor
The UK has an ageing population where there are nearly 12 million people aged 65 or over in the UK, a number which is increasing every year. Across the world people are living longer and the number of centenarians (people reaching 100) has increased by 8% in the past 15 years. By 2030 it is estimated there will be over 21,000 centenarians.
This increased life expectancy means we are exposed to many conditions that were not previously encountered as our bodies simply didn’t last that long. As explained by AgeUK the increase in life expectancy has risen more quickly than healthy life expectancy meaning the number of years spent with chronic and complex health conditions is increasing. This has led to researchers trying to try and slow down the ageing process so quality of life can improve and people can age well.
A key step has been taken in the world of ageing research this year through work at the Buck Institute. They have performed a longitudinal and functional study of 700 mice in order to track how the mice age. They regularly monitored clinically significant ageing changes including blood glucose, body composition, activity levels, metabolic markers and skeletal ageing in bone to see how the mice aged and how this could be improved in the future. During this process they were able to test several potential therapeutics and see if they extended the lifespan or reduced neurological disease, giving mice a higher quality of life.
A focus for the researchers was bone. Through ageing bone mass decreases meaning bones are weaker and people are at an increased risk of fracture. This is caused by a number of processes including a reduction in physical activity, hormonal changes and metabolic changes leading to a loss of calcium in bone. This is a big problem for healthcare with the incidence of fractures increasing with age and around 255,000 admissions to A&E for fractures in people aged over 65. These often lead to rehabilitation problems and disability.
As a means to counteract this the researchers looked at potential therapeutics. Of particular note was the effect of Benzoxazole. This compound had been previously shown to extend the lifespan of nematodes in 2011. Based on this study, researchers decided to test it in the lab mice. They found it slowed bone ageing by up to 31% over the course of a year’s treatment. The effect of the compound on bone was particularly surprising as nematodes are boneless creatures, suggesting the molecule has additional benefits not previously recognised.
Reflecting on this, Buck professor, Gordon Lithgow, said:
“If you have a therapeutic that extends lifespan in a simple animal that has no bone whatsoever, you certainly wouldn’t predict that it would slow the rate of bone aging in a mammal. It’s obvious that aging-related pathways have been conserved during evolution. This new finding is a great example of the utility of screening compounds in simple animals as the starting point to look for unexpected and surprising benefits in mammals.”
This findings is also relevant to human health, as explains senior author of the paper, Simon Melov: “The metrics we used are all directly applicable to aging in humans. They literally have direct clinical correlates to the types of things you would measure in humans.” The exact mechanism behind the reduced bone ageing is not currently known but is a site of current research and one that can be expected to see human applications in the near future.
As well as the findings of Benzoxazole, the results of this study are expected to change the field for years to come. It has created a labyrinth of data for other researchers to use. Many experiments are preceded by pre-clinical studies to find the ideal number of animals needed and the time period required; these steps can now be skipped by researchers using this database as their pre-clinical trial.
On this, Melov said:
“We think using this new database could save substantial resources for those wanting to do preclinical studies on interventions. If someone wants to test a compound against a particular aging phenotype this database could provide information about how many mice are needed for the experiments and how long it would likely take to see results”.
A key principle of animal testing is the 3Rs meaning the number of animals used is minimal, they are only used when needed and the potential for suffering is reduced wherever possible. These principles govern ethical approval on animal studies so the being able to reduce the number of animals needed as a result of this database is a huge step forward for the sector and can be expected to increase the rate of research in the future.
The database from the Buck Institute will be used by researchers for years to come, where it is hoped that the results of Benzoxazole can be realised. It provides a new potential therapy which both increases our understanding of bone ageing and may give us another weapon to fight it.