December 6, 2010

Aspects of Aging Might Be Reversed

Microscope image of blue chromosomes with green dots at tips Telomerase (green) was turned on to restore telomeres at the ends of chromosomes (blue).Jaskelioff et al, courtesy of Nature.

Researchers have reversed age-related degeneration in a mouse model of aging. While the findings don’t prove that natural aging could be halted or reversed, they may lead to new strategies to combat certain age-related conditions.

Several studies have tied shortened telomeres to age-related diseases and early death in humans. Telomeres are sections of specialized DNA and proteins that cap the ends of chromosomes and prevent them from unraveling. With each cell division, telomeres erode slightly—although they can be rebuilt by the enzyme telomerase. When telomeres become too short, the cell stops dividing or dies.

In the laboratory, the telomerase enzyme has been found to help certain types of cells divide indefinitely or live longer. A team of researchers led by Dr. Ronald A. DePinho of the Dana-Farber Cancer Institute at Harvard Medical School set out to explore whether boosting telomerase activity could make a difference in living animals. Their investigation was supported partly by NIH's National Cancer Institute (NCI).

The researchers began with telomerase-deficient mice. These animals prematurely undergo the DNA and tissue degeneration normally seen in older mice. The scientists genetically engineered a telomerase gene into the mice that could selectively be turned on with a compound called 4-OHT.

As reported on November 28, 2010, in the advanced online edition of Nature, 4 weeks of 4-OHT treatment reversed many aspects of the aging process. The mice had longer telomeres, various rejuvenated tissues and gave birth to larger litters. They also lived longer than untreated telomerase-deficient mice—although still not as long as normal mice.

Telomerase reactivation also quickly affected the brain, leading to the growth of new neurons and an increase in brain size. "When we flipped the telomerase switch on and looked a month later, the brains had largely returned to normal," DePinho says.

To investigate functional improvement in the brain, the scientists tested whether the mice would avoid an odor that mice are known to dislike. People and mice both tend to lose the ability to detect and distinguish odors with increasing age. The telomerase-deficient mice didn't avoid this particular odor. However, telomerase reactivation led the mice once more to avoid the odors.

While these findings are preliminary, they do suggest that regenerative strategies aimed at restoring telomeres might reverse some of the effects of aging. “Whether this would impact on normal aging is a more difficult question,” DePinho says. “But it is notable that telomere loss is associated with age-associated disorders and thus restoration of telomeres could alleviate such decline.”

—by Harrison Wein, Ph.D.

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