Shared Ageing Research Models (ShARM) is a not for profit organisation for sharing resources on ageing mice models. Funded by the Wellcome Trust, ShARM is a partnership between MRC Harwell and the Universities of Sheffield and Newcastle. ShARM Community offers access to aged mice models to researchers in the UK and abroad and encourages exchange of knowledge and ideas.
ShARM is a great example of how collaborations, sharing resources and networking can help accelerate research progress and reduce the number of animals used in research. One of the ShARM Board Members, Professor Tom Kirkwood CBE from the renowned Newcastle University’s Institute for Ageing, one of the largest academic institutes in the world studying ageing, shares his views on ShARM.
Professor Kirkwood has had a huge contribution in the area of biology of ageing and is considered a world leader in the field. His research aims to understand the basic science of ageing. He was Specialist Adviser to the House of Lords Science & Technology Select Committee inquiry into ‘scientific aspects of ageing’ and has served on the Councils of BBSRC and the Academy of Medical Sciences. Professor Kirkwood led the first study in the UK looking at the lives of 85+ year olds: the MRC-funded Newcastle 85+ Study, with more than 1000 participants. He is also an author of award-winning books and more than 300 scientific papers.
Two decades ago
Do tissue stem cells lose their functions with age? This was the question that the late Chris Potten and I wanted to answer nearly twenty years ago. At the time it was generally supposed that stem cells might be immune to the effects of ageing but no one really knew. The question seemed, at least in principle, easy enough to address. What we needed was to get hold of samples from mice of different ages, ranging from young to old, and to study them. Very fortunately, we had access to just the right source – a colony of aged mice that had been maintained for some years specifically for this kind of purpose. We were able to run pilot studies on just a few animals, which provided the evidence to support a successful grant application, which in turn provided the definitive answer to our question: yes, they do.
But suppose we had been unable to source the aged tissues we required. To begin the work we would have needed to acquire young mice, set them aside to grow older, and wait for at least two years before we could start work. How many mice would we have needed to set aside, and how would we have paid for them while we waited to get started? These practical obstacles have confronted many a researcher who has considered asking basic questions about ageing and, until the advent of ShARM, they have been hard to overcome.
Working with ‘old’ mice – where to start when you have to wait two years for a model?
The fundamental issue with the supply of mice for ageing research relates to the organisation of aged-rodent colonies. In order that researchers can gain immediate access to tissues from old animals, someone must have had the foresight to age them earlier. Yet the design and successful operation of an aged-rodent colony is far from simple. The key issues are cost, quality, forward planning, efficiency and animal welfare. The issue of cost alone is itself daunting. To keep a mouse until it is two or more years old, which is when it begins to become interesting from the ageing perspective, is very expensive. Not only do the animal house charges need to be paid for each week of this time, but the costs escalate much faster than linearly at the higher ages, because the oldest mice are the survivors from an initial birth cohort. The minimum actual cost of a very old mouse (several hundred pounds) therefore reflects the total cost of keeping the birth cohort to advanced old age.
Forward planning: quality and quantity
The issue of quality is also of paramount importance. If mice are to be kept for years in an aged-rodent colony, the quality of care must be consistently high. Particular attention needs to be taken towards minimising stress by looking at all the factors to which the animals may be sensitive – these include being aware that animals may be disturbed by changes in their environment (noise, personnel, odours, etc) – and by doing what is possible to supply stimulus through environmental enrichment. Without proper care to the quality of husbandry, changes that are seen in ‘old’ mice might reflect the impact of long-term, chronic stress just as much as intrinsic ageing.
The need for forward planning concerns the thorny problem of working out how many animals to include in successive birth cohorts. Too few and there won’t be enough for needs that may not become apparent at the outset. Too many and mice will reach the ends of their natural lifespans without being used for meaningful research. Not only is such an outcome wasteful, but it is also seriously unethical. Efficiency means making sure that when an old animal is killed for research, there are researchers who can make use of as many of its organs and tissues as possible. Once again the concern is to minimise, for both ethical and financial reasons, the numbers of animals that are needed.
ShARM to the rescue
ShARM exists to help resolve many of the above problems. It still requires that someone takes the initiative to establish cohorts of aged mice and operates them to the highest standards of care. But it provides the means to avoid wasting tissues from animals that reach old age and it provides for greatly increased efficiency from sharing of spare organs and tissues. Above all, by providing access to banked tissues from animals of different ages, it makes getting started into ageing rodent research so very much easier.
Research using archived tissue from ShARM includes a group at the University of Sheffield, who looked at bladder physiology in both young and old mice to check if the oxidative stress affects the urothelium (lining of the bladder) and plays a role in ageing. The researchers talked about their experience in the ShARM Newsletter: “Publishing this paper would have been challenging without the tissues from ShARM, and having donated tissues, we are able to include this as a collaborative/ethical action in future funding applications, to demonstrate dedication to the 3Rs.”