Scientists interested in studying successful aging and longevity have found a particularly good example: the naked mole rat. When kept in laboratories, these burrowing rodents have been reported to live nearly 30 years, making them the longest-lived rodent known.
A study by researchers at the Barshop Institute for Longevity and Aging Studies at the University of Texas in San Antonio reveals mechanisms in the cells of naked mole rats that could explain their impressive longevity. Compared with mice (which typically live three to four years), naked mole rats have better ways of maintaining the health of proteins in their cells, according to the study, published this week in Proceedings of the National Academy of Sciences. Coauthor Rochelle Buffenstein, a physiologist at the Barshop Institute, says that uncovering tricks that slow-aging animals use to extend their life span could point to strategies for alleviating diseases of aging in humans.
Buffenstein has been studying the naked mole rat for decades but recently became interested in the animals as “a model to study successful aging.” Although their pale, wrinkled skin and poor eyesight might not evoke the picture of health, mole rats not only live a long time, but they also seem to experience healthier aging than most animals. They have little incidence of cancer and few signs of bodily degeneration; females can breed up until their death.
One long-standing theory of aging is that it results from the slow degeneration of cells through contact with oxygen, called oxidative stress. But paradoxically, naked mole rats have higher levels of oxidative damage in their cells than do mice, even from a young age. To understand why these animals seem to be resistant to the effects of oxidation, Buffenstein and her colleagues at the Barshop Institute looked at the rodents’ proteins, one of the key targets of oxidative damage.
Buffenstein worked with biochemist Asish Chaudhuri to compare the structure of proteins in the liver tissue of old and young naked mole rats to those in mice using high-throughput methods recently developed in Chaudhuri’s lab. The analyses showed that proteins in mole-rat cells are more resistant to unfolding, making them more stable than those of mice.
The researchers also found evidence that the cells of mole rats have more efficient mechanisms for getting rid of improperly folded or oxidized proteins. Buffenstein says the results suggest that naked mole rats can withstand oxidative damage better by keeping their proteins stable and quickly removing unfolded proteins before they can accumulate.
Matt Kaeberlein, a scientist at University of Washington who studies aging in worms, says, “It’s been a mystery for a long time as to why these naked mole rats are so much longer lived than mice.” He says that the current study provides strong evidence that “one of the things that potentially underlies the extreme difference in life span in these animals” is their ability to maintain the health of proteins in cells.
Proteins are constantly unfolding and refolding, and can lose their proper shape or get damaged. Over time, the body loses the ability to deal with defective or improperly folded proteins, and they can accumulate and become toxic to cells. Indeed, the unhealthy aggregation of proteins in brain cells has also been implicated in several diseases of aging, including Alzheimer’s and Parkinson’s. This latest study, says Kaeberlein, fits well with research in other species suggesting that quality control of proteins is a key part of healthy aging.
“Our first plan is to try and identify the proteins that protect and are protected in naked mole rats,” says Buffenstein. It may be that only certain proteins are critical for keeping cells healthy; for instance, naked mole rats may have differences in a class of proteins called chaperones, which help stabilize proteins by keeping them properly folded. The researchers believe that once these targets have been identified, it may be possible to mimic the protective strategies of naked mole rats in order to prevent aging-related disease in humans.
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