For years, scientists have studied the effects of aging on the brain; today this study reaches the single-cell level. Using innovative brain mapping tools, and as part of the NIH BRAIN Initiative, these scientists were able to examine the brain both more holistically and in more detail.
“Aging is the greatest risk factor for Alzheimer’s disease and many other devastating brain disorders. Our work provides a very detailed map of which brain cells may be most affected by aging,” summarizes lead author Dr. Richard J. Hodes, director of the National Institute on Aging at the NIH: “Our data clarify how “aging affects the brain and provides a guide for the development of new treatments for age-related brain diseases.”
Not all types of brain cells age in the same way
The study reveals that some cells, including a small group of cells controlling hormones, may undergo more age-related changes in their gene activity or expression than others. Specifically, using advanced genetic analysis tools, researchers tracked individual cells in the brains of 2-month-old “young” mice and 18-month-old “old” mice. For each age, the researchers analyzed
the genetic activity of 16 large brain regions representing 35% of the total brain volume.
Analysis of this data reveals:
- a decrease – unsurprisingly – with age in the activity of genes associated with neuronal circuits;
- these decreases in expression are observed in neurons, primary circuit cells, as well as astrocyte and oligodendrocyte “glial” cells, which can support neuronal signaling by controlling neurotransmitter levels and electrically insulating nerve fibers;
- an increase with age in the activity of genes associated with the brain’s immune and inflammatory systems, as well as brain blood vessel cells.
Cell types more sensitive to aging:
- aging reduces the development of newborn neurons present in at least 3 regions of the brain;
- some of these newborn neurons could play a role in circuits that control certain forms of learning and memory, while others could help recognize different odors;
- The cells most susceptible to aging surround the third ventricle, a conduit that allows cerebrospinal fluid to pass through the hypothalamus. Located at the base of the brain, the hypothalamus produces hormones that can control the body’s basic needs,
including temperature, heart rate, sleep, thirst and hunger;
- These cells that line the 3rd ventricle of the brain and neighboring neurons of the hypothalamus show the greatest changes in genetic activity with age, including an increase in immunity genes and a decrease in genes associated with neuronal circuits.
Clearer links between aging and body metabolism: these observations help explain the links between age and metabolic changes. They also shed light on how intermittent fasting and other low-calorie diets may increase lifespan. Specifically, age-sensitive neurons in the hypothalamus are known to produce food and energy controlling hormones while ventricular wall cells control the passage of hormones and nutrients between the brain and the body.
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