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Genetically modified mice live longer

2 September 2013
Appeared in BioNews 720

Scientists have extended the lifespan of mice by partially suppressing a gene associated with cell growth and metabolism.

The team of researchers National Institutes of Health (NIH), USA, engineered mice that produced only 25 percent of the normal level of protein expressed by a gene called mTOR. They found that the median lifespan for the mTOR mice was extended by about 20 percent in both males and females, the equivalent of increasing the average human lifespan by 16 years.

The team also noted that the genetically influenced mice outperformed normal mice of similar age in maze and balance tests, indicating improved memory and coordination. Older mTOR mice also retained more muscle strength and posture. However, as these mTOR mice aged, they had less bone volume and were more susceptible to infections. This implied that the mTOR gene affected tissues differently.

'While the high extension in lifespan is noteworthy, this study reinforces an important facet of ageing; it is not uniform', said lead author Dr Toren Finkel at NIH's National Heart, Lung, and Blood Institute. 'Rather, similar to circadian rhythms, an animal might have several organ-specific ageing clocks that generally work together to govern the ageing of the whole organism'.

Dr Joseph Baur, a researcher at the University of Pennsylvania who was not involved with the study, told The Scientist 'that this was the first study to use a genetically induced reduction of mTOR resulting in lifespan extension among both sexes of mice'.

Looking ahead, Dr Finkel noted 'that these results may help guide therapies for ageing-related diseases that target specific organs, like Alzheimer's'.

The exact mechanism by which mTOR regulates a person's lifespan remains unclear. Professor Dominic Withers from Imperial College London, who was not involved in the study, told The Scientist 'that ageing in these mutant mice is likely delayed by a combination of effects involving mTOR inhibition. Reduction of mTOR signalling may mimic the effects of dietary restriction - which in itself is not fully explained as a mechanism'.

However, Dr Finkel concedes that further studies in these mice as well as human cells are needed to identify exactly how ageing in these different tissues is connected at the molecular level.

The study is published in the journal Cell Reports.

SOURCES & REFERENCES
Genetic Manipulation Extends Life of Mice 20%
Wall Street Journal |  29 August 2013
Increased Mammalian Lifespan and a Segmental and Tissue-Specific Slowing of Aging after Genetic Reduction of mTOR Expression
Cell Reports |  29 August 2013
Mutant Mice Live Longer
The Scientist |  29 August 2013
Single gene change increases mouse lifespan by 20 percent
National Heart, Lung and Blood Institute (press release) |  29 August 2013
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