A protein associated with youth may help aging brain cells regain some of their lost abilities. Scientists at the Icahn School of Medicine at Mount Sinai have discovered that TIMP2 plays an important role in keeping the brain's immune cells healthy, offering new clues about how the brain changes with age. In a study published in Nature Communications, researchers found that removing TIMP2 caused brain immune cells, known as microglia, to develop characteristics linked to aging and neurodegenerative disease.
When the scientists restored TIMP2 in the bloodstream of older mice, these cells became better at removing cellular debris and showed fewer molecular signs of inflammation and other potentially harmful changes. The discovery suggests that proteins associated with youth may help preserve the brain's natural defenses as it ages. It also identifies TIMP2 as a potentially important factor in maintaining healthy immune activity in the brain.
Why the Brain's Immune Cells Become Less Effective With Age Getting older is the greatest known risk factor for Alzheimer's disease and other neurodegenerative disorders. However, scientists still do not fully understand the biological processes that make the aging brain increasingly vulnerable to these conditions. One important piece of the puzzle involves microglia, specialized immune cells that serve as the brain's maintenance and defense system.
They remove cellular waste, help maintain the networks through which neurons communicate, and respond when brain tissue is injured. As the brain ages, these cells can lose some of their ability to perform these essential tasks. They may also shift into states that promote inflammation and interfere with normal brain function.
"TIMP2 facilitates healthy function for the brain's immune cells," said Joseph M. Castellano, PhD, Associate Professor of Neuroscience at the Ronald M. Loeb Center for Alzheimer's Disease and The Friedman Brain Institute at The Icahn School of Medicine at Mount Sinai, and corresponding author of the study.
"By supporting the ability of microglia to clear debris and limit maladaptive responses, TIMP2 may help restore aspects of microglial function that become compromised with age. Since our previous work identified TIMP2 as a regulator of synaptic plasticity through the extracellular matrix, these findings suggest that this factor sits at the intersection of several processes that are critical for normal brain function." Synaptic plasticity refers to the brain's ability to strengthen or weaken connections between neurons, a process essential for learning and memory. The extracellular matrix is a network of molecules surrounding cells that helps support and regulate their activity.
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