The naked mole-rats (Heterocephalus glaber) are very unusual burrowing rodents from Eastern Africa. Mole rats live in underground colonies of 20 to 300 animals, and are unique amongst vertebrates with their social system similar with that find in some insects (like ants, bees or termites). Only one female (the queen) and one to three males reproduce, while the rest of the individuals function as workers! Workers have 30-35 g while the queen can weigh 50 to 80 g (the same differences of size occur in bees)! Workers can be tunnelers (which dig with their teeth) or soldiers.
Unique amongst mammals, they are virtually cold blooded. They cannot regulate their body temperature at all and requires an environment with a specific constant temperature in order to survive. Another surprising trait of these rodents is their lifespan. While mice of the same sizes life 3 years at most, the naked mole rat can live till the age of 28. Recently scientists found that the naked mole-rat shows much higher levels of oxidative stress and damage and less robust repair mechanisms than the common mouse. This contrasts with the oxidative stress theory of aging, which claims that damage caused by oxidative stress is a significant contributor to the aging process.
According to the theory, the naked mole-rats should present lower levels of oxidative stress than their shorter-lived relative. "Don't toss
the oxidative stress theory of aging out the window just yet, but prepare to modify it," said Rochelle Buffenstein, of the City College of New York.
The naked mole-rat's longevity may be caused by its ability to defend against acute bouts of oxidative stress that happens because of an unusual occurrence rather than as a result of normal aerobic respiration, as the experimental results showed. "For example, when hydrogen peroxide (a powerful oxidant substance) is added to a culture containing naked mole-rat fibroblast cells, they remain viable and appear to repair the acute damage more rapidly than shorter-lived animals," explained Buffenstein.
"They (naked mole rat and common mouse) re the same size and they're (closely related) rodents, but the mole-rat lives to 28 years, about nine-times longer than the mouse."
"Mole-rats must have something happening at the biochemical level to allow them to do this," said Blazej Andziak, from the same City College, NY.
The normal oxidative stress occurs during the burning phase of the metabolism when oxygen molecule (O2) splits into single oxygen atoms (free radicals), which circulate by themselves or combine with molecules, forming reactive oxygen species (ROS). ROS can damage functional molecules (DNA, lipids and proteins) thus impairing normal cellular function. Antioxidants neutralize ROS, decreasing their activity.
The study compared two-year-old naked mole-rats to four-month-old mice to be of equivalent ages compared to their lifespans. The team measured the level of reduced glutathione (an antioxidant) against oxidized glutathione. The ratio of reduced/oxidized glutathione indicates the level of oxidative stress: more reduced gluthathione means less oxidative stress.
When they measured this ratio in the liver, they found it higher in mouse than in mole-rat, which contradicted the theory of aging. So the mole-rats experienced more oxidative stress.
Andziak had previously found that glutathione peroxidase, the antioxidant enzyme, had much lower activity in mole-rats than in mice. Looking for damage caused by oxidation in cellular molecules, they found it at much greater levels, in all tissues studied, when compared to mice.
The study found multiple signs of lipid damage: The level of isoprostanes found in the urine was 10 times higher in the naked mole-rat, the level of malondialdehyde in liver tissue was twice as high and isoprostane levels in heart tissue was two-and-a-half times the level of the mice. The kidney and heart presented significantly more protein damage and the DNA damage was greater in the kidney and liver. "All of the classical measures of oxidative stress are higher in the mole-rat," Andziak concluded. "Given that naked mole-rats live an order of magnitude longer than predicted based on their body size, our findings strongly suggest that mechanisms other than attenuated oxidative stress may explain the impressive longevity of this species."
Buffenstein said "the mole-rat is able to fend off the occasional oxidative insult that can occur, and that may be more important than what happens with the steady-state levels of oxidative stress that result from normal metabolic activity."
The naked mole-rats in the laboratory may suffer higher levels of oxidative stress than they would in their natural underground habitat, less aerated. "But this exposure at an early age may provide some protection against acute oxidative stress and may be of considerable importance in their resistance to bursts oxidative stressors throughout their lives," she said.
"The naked mole-rat, with its surprisingly long lifespan and remarkably delayed aging, seems like the perfect model to provide answers about how we age and how to retard the aging process," Buffenstein said.
"This animal may one day provide the clues to how we can significantly extend life."
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