Harvard researchers at Dana Farber Cancer Institute have successfully engineered mice with a controllable telomerase gene that partially reverses aging. The findings could be applied for helping humans with age related problems, particularly those with rare genetic premature aging disorders and possibly the rest of us.
Telomeres that are part of DNA erode with aging. Longer telomeres are linked to a longer lifespan. The Harvard scientists tested the genetically engineered controllable gene in mice, finding that switching the teleromase enzyme off caused them to age, while reactivating the gene reversed many aspects of the aging process. The mice regained cognitive functioning and became fertile from new brain and testes growth.
Researchers Reverse many Signs of Aging in Mice
The scientists found many signs of age reversal in the mice, including increased size of testes, brain and spleen. Ronald A. DePinho, a Harvard Medical School (HMS) professor of genetics says, “One of the most amazing changes was in the animals’ testes, which were essentially barren as aging caused the death and elimination of sperm cells. When we restored telomerase, the testes produced new sperm cells, and the animals’ fecundity was improved — their mates gave birth to larger litters.”
He also says flipping the gene back on reversed signs of aging in the brain. “More newborn nerve cells were observed, and the fatty myelin sheaths around nerve cells — which had become thinned in the aged animals — increased in diameter. In addition, the increase in telomerase revitalized slumbering brain stem cells so they could produce new neurons.” The mice who had lost their sense of smell regained the sense that is necessary for survival – an activity the scientists used to test functional improvements in the mice. They also showed no signs of developing cancer.
The way the researchers accomplished age reversal was by using the mouse’s own teleromase gene known as TERT, rather than giving them a supplemental gene. They then engineered TERT to include a fusion protein that would only become activated with a special type of estrogen. When they used the estrogen to flip the gene from off to on, they found many signs of aging reversal in the mice after four weeks.
DePinho says it’s a difficult question as to whether the findings could apply to humans, “But it is notable that telomere loss is associated with age-associated disorders and thus restoration of telomeres could alleviate such decline.”
He says the age reversal accomplished in mice could be applied to humans because the findings show adult stem cells in aging tissue can be reactivated and repaired. Telomere shortening causes cells and tissues to fail explains DePinho, but if you can keep stem cells active, it may be possible to reverse aging heath issues.