Naked mole-rats are distinguished by an exceptionally long life span in comparison to similarly sized rodents, and a near immunity to cancer. Unlike other mammals, their mortality rates stay fairly constant until very late life. They accumulate all the signs of significant oxidative damage in cells and tissues, but seem resilient to it. Similarly, researchers here note that naked mole-rats do in fact accumulate senescent cells, one of the root causes of aging, but appear resilient to the harmful presence and activities of these cells. Exactly why this is the case has yet to be determined.
Cells become senescent in response to potentially cancerous damage or reaching the Hayflick limit on replication. The vast majority destroy themselves or are destroyed by the immune system, but a tiny fraction linger. They generate signals that spur chronic inflammation, change surrounding cell behavior for the worse, and destructively remodel nearby tissue structures. This results in functional decline in organs and other important tissues and systems. It is interesting to see that while there are differences in the detailed behavior of senescent cells between naked mole-rats and other mammals, they nonetheless still generate the same damaging signals, and yet the naked mole-rats appear to shrug it off.
With their large buck teeth and wrinkled, hairless bodies, naked mole rats won't be winning any awards for cutest rodent. But their long life span - they can live up to 30 years, the longest of any rodent - and remarkable resistance to age-related diseases, offer scientists key clues to the mysteries of aging and cancer. That's why researchers studied naked mole rats to see if the rodents exhibit an anticancer mechanism called cellular senescence.
Previous studies indicated that when cells that had undergone senescence were removed from mice, the mice were less frail in advanced age as compared to mice that aged naturally with senescent cells intact. Researchers therefore believed senescence held the key to the proverbial fountain of youth; removing senescent cells rejuvenated mice, so perhaps it could work with human beings. But is eliminating senescence actually the key to preventing or reversing age-related diseases, namely cancer?
Researchers compared the senescence response of naked mole rats to that of mice, which live a tenth as long - only about two to three years. Their unexpected discovery? Naked mole rats do experience cellular senescence, yet they continue to live long, healthy lives; eliminating the senescence mechanism is not the key to their long life span. The researchers found that although naked mole rats exhibited cellular senescence similar to mice, their senescent cells also displayed unique features that may contribute to their cancer resistance and longevity.
The cellular senescence mechanism permanently arrests a cell to prevent it from dividing, but the cell still continues to metabolize. The researchers found that naked mole rats are able to more strongly inhibit the metabolic process of the senescent cells, resulting in higher resistance to the damaging effects of senescence. "In naked mole rats, senescent cells are better behaved. When you compare the signals from the mouse versus from the naked mole rat, all the genes in the mouse are a mess. In the naked mole rat, everything is more organized. The naked mole rat didn't get rid of the senescence, but maybe it made it a bit more structured."