By Rivka Borochov
Cats may live nine lives, and some species of coral live for 4,000 years. But cracking the secret elixir to longer life in human beings might make this one the year of the rat. Rodent expert Dorothee Huchon from Tel Aviv University in Israel has helped unlock the information to long life found in the genes of the naked mole rat, a rodent native to East Africa.
Knowing more about the special proteins made by this rodent’s brain could help scientists in the future prepare drugs to help humans live longer, more productive lives.
Compared to humans at an advanced age, this little hairless rodent -- also known as a sand puppy or desert mole rat -- shows little evidence of aging. It stays active through all stages of life, it enjoys good bone health, reproductive success, and its mind stays healthy.
While the common rat lives on average three years, the naked mole rat, Heterocephalus glaber, can surpass this by far – living from 10 to 30 years. It might not be beautiful, but it lives long.
This new collaborative research study between Huchon and colleagues at the Texas Health Science Center in San Antonio, and the City College of New York, determined that the naked mole rat’s unusual life expectancy is due to very high levels of a neuro-protective protein called Neuregulin (NRG-1) in its brain. The protein is also found in the human brain. In fact, the interaction of NRG-1 with other brain proteins is believed to be a cause of schizophrenia. Some researchers have found the NRG-1 gene can act as a tumor suppressor, can protect the brain against stroke, and a variant of the gene can lead to higher levels of creativity.
The mole rat might help science tap into the power of this potent protein.
The new study, whose results were recently published in the science journal Aging Cell, set out to determine if the NRG-1 protein is responsible for the rodent’s successful and long life. The DNA of this particular species shows a striking similarity – about 85 percent -- to the DNA of humans. Knowing more about NRG-1 in rats could very well lead to new advances for longer life in people.
Teasing out evolutionary relationships
In the study, Huchon conducted a genetic analysis that compared the mole rat with other rodent species, while her partners looked at the activity of NRG-1 in rodent brains.
Rodent expert Dorothee Huchon The US researchers measured NRG-1 levels in naked mole rats throughout the age range of one day to 26 years, and found it was in constant supply. The biggest concentration was in the cerebellum, an area of the brain involved in motor control.
Just how strong is the correlation between the level of the protein and the fitness of this species? Evolutionary biologist Huchon looked at seven species of rodents, including guinea pigs, mice and rats, to determine if long life was a trait that evolved in a way unique to the mole rat. She used a process called phylogeny (the history of the evolution of a species or group) to determine if the protein or something else was the causal effect of long life.
“In my day job I am working on rodent relationships, not aging,” says Huchon. In this study, “my knowledge on rodent relationships was used to help other researchers –– to give them a framework to describe the evolution of proteins.”
“We needed to know who is closest to whom, in the case of aging. If there are two species that live a long time, is it because they are related or because they [have proteins] that evolved in different pathways?”
She found that the mole rat’s life span was independent of phylogeny, meaning that its tendency to long life had evolved in a unique way compared to other rodents.
The researchers believe that this research is a first but important stage toward learning how aging and NRG-1 are related. Since mole rats have also been useful in biomedical research due to their resistance to cancer, there may be deeper consequences for human health if more is known about the functioning of NRG-1.