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August 30, 2012

Making the study of aging faster and more affordable through intelligent collaboration

SENS - A new Shared Ageing Research Models (ShARM) will make the testing and development of antiaging faster and more affordable.

The new Shared Ageing Research Models (ShARM) resource is now up and running. Headed by CIMA mesenchymal stem cell biologist Dr. Ilaria Bellantuono, ShARM uses a collaborative, decentralized, and "lean" approach to increasing scientists' access to aging animals for biogerontology research. The approach is quite different from the system used by the NIA. Instead of providing more mice to the scientists that need them for research, ShARM gives more scientists access to the limited supply of aged animals and tissues that are already in the British and international research system, allowing them to unlock lifesaving information out of biological materials that would otherwise be lost to science.

Imagine a biogerontologist who has raised a colony of rats into senescence in order to study (for example) the relationship between age-related decline in cognitive function and associated changes in hippocampal gene expression. She runs the aged animals and young controls through a Morris water maze, and then sacrifices them to obtain brain tissue for a microarray study. Under status quo ante, two or three years' worth of investment in those mice -- and an unquantifiable amount of additional data on the impact of aging on the remainder of the aged organism -- would simply go out in the biological waste material stream. But by participating in ShARM's biorepository, the researcher can open up access for multiple additional laboratories to mine what the degenerative aging process has seared into the same animals' otherwise-forfeited tissues and serum.

To participate in ShARM, the original researcher collects and flash-freezes multiple young-control and old animal tissues in accordance with a standardized protocol -- tissues that would otherwise be so much biological waste material. A small fund is available within ShARM to award researchers whose samples meet certain minimum criteria with up to £55 per donated mouse; these monies not only defray the original researcher's costs for raising the animals (and for then harvesting, submitting, and documenting the tissues), but incentivize donation and the taking of the care required to submit better-quality tissue samples.



These are then stored at a secure and proficient tissue bank, along with documentation of the samples' provenance. Researchers looking to perform studies with such tissues can then browse the biorepository databases and select samples that meet their research needs. The cost to the second (and, potentially, third, fourth, or more) researcher to obtain these samples is minimal: just a small administrative fee (£35/tissue) to help ensure the sustainability of ShARM as a nonprofit organization, amounting to about a third of what live aged animals cost when purchased from the NIA even with its generous subsidy, and a much smaller fraction of what it would have cost to raise an entirely new colony of animals for each of the several studies that might now make use of the animal's tissues.

In addition to banking tissues from already-sacrificed animals, ShARM also maintains an anonymized database of live colonies of aging animals, including information on information on rodent strain, current age, expected time of sacrifice, and husbandry. The database thus acts as matchmaker or clearing house for collaboration between researchers maintaining live colonies of aging rodents and other scientists needing bespoke or non-frozen tissue samples, or even to generate a side-project in an ongoing live animal study.

ShARM is also a very open program, giving quick and inexpensive access to tissues and serum of animals that have undergone degenerative aging to any legitimate biogerontology researcher in Britain and across the world. The availability of both banked and on-demand tissue samples, and the opportunity for collaboration with principal investigators with registered live animal colonies, makes it possible to move from conceptualizing an experiment to executing it in far less time, and with far fewer logistical requirements, than had previously been possible except through informal personal networks. In our hypothetical example, the original investigator was focused on the brain, but her participation in ShARM would allow other investigators to perform studies on the histology of the same animals' muscles and kidneys; on metabolomic or glucoregulatory changes in the serum; or on any number of additional subjects outside of the original researcher's specialty and beyond her budget or technical capacity to investigate, or the outside investigators' ability to support with animals of their own.

Handling mice for two years can cost $1400 per mouse

If half your mice live to age 24 months, then producing a single 24 month old mouse requires you to pay someone to house two mice for 24 months, one of which has just died. If only 10% of the mice survive to age 32 months, then the real cost of each 32 month old mouse is the cost of raising 10 mice for anywhere from 18 to 32 months to get the one alive at 32 months. ... The nominal cost of a 32 month old mouse (at $0.58/cage/day) is $140, but adjusting for attrition and disease gives a real cost closer to $1,400 each.
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