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A new study published in Physiological Genomics suggests that the brain shows signs of aging earlier than old age. The study found that the microglia cells—the immune cells of the brain—in middle-aged mice already showed altered activity seen in microglia from older mice.

Parkinson’s, Alzheimer’s and other aging-related neurodegenerative disorders are associated with excessive inflammation in the brain. Scientists believe that overactive microglia cells contribute to the excess inflammation. Normally, microglia protect the brain from infection and ensure the brain functions properly. Their immune response is tightly controlled. Microglia produce pro-inflammatory molecules to turn the inflammation process on, followed by anti-inflammatory molecules to turn inflammation off. With aging, microglial cells can overreact, and their immune activity can become less controlled—they turn inflammation on too quickly or turn it off too slowly. The prolonged or constant inflammation that results can damage the brain.

While it is known that microglia immune activity changes with aging, which response is affected first—the pro-inflammatory or the anti-inflammatory—or, more importantly, when microglial aging begins is not clear, says Jyoti Watters of the University of Wisconsin-Madison and lead investigator of the study. “We show in a mouse model that it may begin earlier than we thought,” Watters says.

The research team at the University of Wisconsin-Madison studied the microglia activity of young (two months old) and middle-aged (nine to 10 months old) mice. The researchers injected the mice with lipopolysaccharide, a molecule found in bacteria that strongly activates the immune system and causes inflammation. The mice were injected twice to assess the microglia’s ability to reset their immune activity and respond to another bout of inflammation.

The researchers found that middle-aged mice displayed exaggerated pro-inflammatory responses after the first injection. However, anti-inflammatory responses were normal. After the second injection, both pro-inflammatory and anti-inflammatory responses were normal. The data suggest that at middle age, the microglia already showed signs of an altered immune response. But not everything is impaired: The microglia of the middle-aged mice still responded normally to the second injection. “At this time, age-related alterations may only be beginning since other critical capacities have not begun to deteriorate yet,” according to Watters. “Of course, it is not known when aging-associated changes in microglial activities begin in the human brain, but these results in mice suggest that it may be earlier than we had previously appreciated,” Watters says.

.Newswise

When one eats may be as important as what one eats. New research at the Weizmann Institute of Science and in Germany, which recently appeared in the Proceedings of the National Academy of Sciences (PNAS), suggests that the cells’ power plants – the mitochondria – are highly regulated by the body’s biological, or circadian, clocks. This may help explain why people who sleep and eat out of phase with their circadian clocks are at higher risk of developing obesity, diabetes and metabolic syndrome.

Dr. Gad Asher of the Weizmann Institute’s Biomolecular Sciences Department, who led the study, explains that circadian clocks, which are found in living things from bacteria to flies and humans, control our rhythms of sleep, activity, eating and metabolism. “In a sense,” he says, “it’s like a daily calendar, telling the body what to expect, so it can prepare for the future and operate optimally.”

Dr. Adi Neufeld-Cohen, of Asher’s group, in collaboration with Dr. Maria S. Robles and Prof. Matthias Mann of the Max Planck Institute of Biochemistry in Germany, looked for circadian changes in the mitochondria that, by creating peaks and dips in the cells’ energy levels, would also help regulate their day-night cycles. The group identified and quantified hundreds of mitochondrial proteins, finding that the quantities of a whopping 40% peak once a day. Further research identified the proteins making up the mitochondrial circadian clock that regulates these activities. Surprisingly, most of the circadian proteins in the mitochondria peaked four hours into the daylight part of the cycle (in mice, which are active at night).

Among the essential proteins the researchers uncovered was a key enzyme that determines the rate of sugar use for energy production. This protein reaches its maximal amount four hours into daylight, suggesting that the mitochondria’s capacity for burning sugar peaks around this time, as well. To check, the researchers provided mitochondria with sugar and found that at around hour four, respiration and glucose utilization were indeed at their highest. They also found that the protein responsible for the entry of fatty acids into the mitochondria only peaks at the eighteenth hour and, again, tests showed fat processing was optimal at the same time.

In mice with a genetic mutation that interferes with their overall biological clocks, the amounts of these proteins did not change over the course of the day, and the decomposition activity of fats and sugars was steady throughout.

“These findings support previous findings in our lab in which we showed that if mice eat only at night, when they are active, rather than throughout the day and night, they will eat the same amount of calories but their liver lipid levels will be 50% lower,” says Asher. “In other words, the outcome depends not only on what you eat but also on when you eat it. If we could be more aware of the timing of our cellular activities, we might be able to take advantage of various nutrients in a healthier way.”