Mouse Lifespan Increased 20% by Single Gene Alteration

The researchers targeted a gene called mTOR, which is involved in metabolism and energy balance, and may be connected with the increased lifespan associated with caloric restriction.

A detailed study of these mice, published in the August 29, 2013, of the journal Cell Reports, revealed that gene-influenced lifespan extension did not affect every organ and tissue in the same manner. For example, the mice retained better memory and balance as they aged, but their bones deteriorated more rapidly than normal.

“While the high extension in lifespan is noteworthy, this study reinforces an important facet of aging; it is not uniform,” said lead researcher Toren Finkel, MD, PhD, at the US National Institutes of Health’s (NIH) National Heart, Lung, and Blood Institute (NHLBI; Bethesda, MD, USA). “Rather, similar to circadian rhythms, an animal might have several organ-specific aging clocks that generally work together to govern the aging of the whole organism.”

Dr. Finkel, who heads the NHLBI’s Laboratory of Molecular Biology in the Division of Intramural Research, noted that these findings may help guide therapies for aging-related diseases that target specific organs, such as Alzheimer’s disease. However, additional research in these mice as well as human cells are required to figure out precisely how aging in these diverse tissues is linked at the molecular level.

The researchers modified mice that make approximately 25% of the normal amount of the mTOR protein, or about the minimum needed for survival. The engineered mTOR mice were a little smaller than average, but they otherwise appeared normal. The median lifespan for the mTOR mice was 28.0 months for males and 31.5 months for females, compared to 22.9 months and 26.5 months for normal males and females, respectively. The mTOR mice also had a longer maximal lifespan; seven of the eight longest-lived mice in this study were mTOR mice. This lifespan increase is one of the largest observed in mice up to now.

Whereas the genetically modified mTOR mice aged better overall, they revealed only selective improvement in specific organs. They typically outperformed normal mice of same age in maze and balance tests, indicating better retention of memory and coordination. Older mTOR mice also retained more muscle strength and posture. However, mTOR mice had more loss of bone volume as they aged, and they were more prone to infections at old age, suggesting a reduction of immune function.

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US National Heart, Lung, and Blood Institute