Partial gene knockout produces long-lived mice
Researchers at the National Institutes of Health have found that suppressing the expression of a single gene in mice extends their average lifespan by about 20 percent – the equivalent of humans living an average of 95 years. While modification of the so-called mTOR gene may not lead to the fountain of youth, further study could open up a path to keeping us healthier and more alert in our old age.
The findings of the NIH study indicate that the median lifespan of the wild-type mice was 25.4 months, compared to 30.3 months for the mTOR-suppressed mice, an increase of over 19 percent. The maximum lifespan of the mTOR-suppressed mice was increased by about 12 percent, to about 1.5 times the median lifespan of the wild-type mice. In human terms, this would correspond to nearly 120 years of age, which is getting close to the 122 years survived by Jeanne Calment, the oldest human on (reliable) record.
There were a mixed bag of other effects on the mTOR-suppressed mice. They tended to suffer more infections and more severe age-related bone density loss than did wild-type mice. On the other hand, the genetically engineered mice had fewer tumors (one of the primary causes of death of laboratory mice), and experienced a slower transition into senility (mental and physical) than did the wild-type mice.
The mTOR gene is associated with metabolism and energy balance, suggesting that its suppression may have effects similar to those of caloric restriction. Previous research has shown that eating a very-low calorie diet increases the lifespan of mice and rhesus macaques, inspiring some people to follow such a diet. However, a recent study of 41 strains of mice found that one-third of the strains showed no change in lifespan in response to caloric restriction, and of the remainder, more strains had shorter rather than longer lifespans. An analysis of the studies on rhesus monkeys showed that if you include all forms of death, they do not on average live longer on calorie restricted diets.
The structure of the rapamycin-FKBP12-mTOR complex - pink is rapamycin, blue is FKBP12, and red is mTOR (Photo: Fvasconcellos via Wikipedia)
The immunosuppressant drug rapamycin shows effects similar to those claimed for caloric restriction. The mode of operation is thought to be suppression of the mTOR gene, which regulates numerous metabolic and inflammation pathways. However, rapamycin does not appear to be a musine fountain of youth. A recent study shows that populations of mice treated with rapamycin do appear to live longer, but the rate at which they age is not slowed. The effect now appears not to be a general slowing of aging (although senility appears to have a slower onset), but rather that fewer premature deaths occur from formation of tumors.
The NIH team decided to study suppression of the mTOR gene in a more focused way. They used a new technique to genetically engineer a strain of mice which produced only about one-quarter of the mTOR protein found in normal mice. They found mTOR suppression does correlate with 20 percent longer lifespan, but there is no consistent slowing of the aging process.
These findings suggest that mTOR suppression could provide benefits to an aging population by keeping people healthier as they get older. This is clearly a worthwhile target for further research, and if such research also reveals how to extend the human lifespan, well, two birds with one stone.
The NIH study was recently published in the journal Cell Reports [PDF].
Source: National Institutes of Health