Genetically modified mice live longer

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.