Methuselah Mouse Prize



The Methuselah Mouse Prize or Mprize is a growing $4.5 million prize started in 2003 to accelerate research into slowing and reversing cellular aging and breakdown in humans. It is governed by The Methuselah Foundation, a non-profit 501(c)(3) volunteer organization whose other interests beside the Mprize include PR work for the acceptance of and interest in scientific anti-aging research and SENS-based research programs, all of which the foundation hopes will lead to a proposed Institute of Biomedical Gerontology.

The Methuselah Foundation awards prizes to researchers who extend the lifespan of a mouse to unprecedented lengths. The prize is named after Methuselah, a patriarch in the Bible said to have reached 969 years of age. Former Cambridge biogerontologist Aubrey de Grey is the chief scientist of the project, and also the co-founder alongside David Gobel. The Mprize has been covered in many news sources, including the BBC and Fortune magazine. The prize broke through the $4 million USD barrier on December 11, 2006.

Prize structure and current record holders
The foundation currently awards the following two prizes:


 * A longevity prize for extending total lifespan
 * A rejuvenation prize focusing on intervention begun at older age

The foundation collects donations in order to increase the size of the prizes. Whenever a record is broken, the researcher receives an amount based on the then current size of the prize fund and the percentage by which they exceeded the previous record.

The longevity prize allows any type of intervention, including breeding and genetic engineering; only a single mouse has to be presented. As of 2005, the record holder was a mouse whose growth hormone receptor had been genetically knocked out; it lived for 1819 days (almost 5 years). The rejuvenation prize deals with peer-reviewed studies involving at least 40 animals, 20 treated and 20 control. Treatment may begin only at mid-life, and the average lifespan of the 10% longest living treated animals is used for the record. As of 2005, this record stood at 1356 days (about 3.7 years); the treatment was calorie restriction.

Until November 2004, the foundation ran a reversal prize instead of the rejuvenation prize, with the following rules: the treatment of the mouse could be started at any age, and days before treatment had started were counted double. The winner was a mouse that did not receive any dietary or pharmacological treatment at all, just an enriched environment. The mouse lived for 1551 days (about 4.2 years).

The mouse strain most often used for studies of lifespan, called C57BL/6, has a normal lifespan of about 3 years, while mice whose grandparents have been caught in the wild are unharmed by inbreeding and live nearly 4 years on average.

The science behind
From his biogerontology work, de Grey believes there to be seven root causes of cellular aging, or as he puts it, "the set of accumulated side effects from metabolism that eventually kills us," all of which are reversible. They are:


 * Cell loss and cell atrophy
 * Nuclear [epi]mutations
 * Mitochondrial mutations
 * Death-resistant cells
 * Extracellular crosslinks
 * Extracellular junk
 * Intracellular junk

For more in-depth info on these and the proposed reversions and obviations regarding these, see SENS: The "seven deadly things" and why there are only seven.

Goals and expectations
The foundation believes that if slowing or reversing of cellular aging can be exhibited in mice, an enormous amount of funding would be made available for such research in humans, potentially including a massive government project similar to the Human Genome Project or by private for-profit companies.

Criticisms
One of the issues that has cropped up is whether the mouse is the most suitable model organism with which to research human aging interventions. It has been argued that the fruit fly (drosophila melanogaster) is an alternative model organism for aging studies. While the fruit fly has only 44% genetic similarity to humans, compared to 85% for the mouse, it is estimated that 75% of human disease genes have a fruit fly version. The argument for the suitability of the fruit fly are that (1) lifespan of the fruitfly (40 days) means that more experiments can be performed, (2) the size and low maintanence per individual means hundreds of thousands can be screened per generation (3) the cost of laboratory maintenance is low (4) ethics approval is not required, and (5) low difficulty in generating genetic modifications in embryos, so it is less technically difficult to generate transgenic animals. However, with respect to surgical methods, the larger the animal, the easier to do surgery (such as bone marrow transplants). .

Based on the above considerations, the mouse is preferable if genetic similarity to humans is given highest weight, or if a question specific to the mouse was being asked; the fruit fly may be a better model for studies of many generations, or if large numbers of mutations are needed.