AGEING AND THE BRAIN
Reducing chronic maladaptive inflammation rejuvenates brain cells in mice Scientists pinpoint a single molecular signalling pathway that could be used to reverse age-associated metabolic and immune dysfunction in mice.
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he quest to slow down or reverse the mental decline triggered by age-related inflammation in the brain has been vigorously pursued. A discovery by scientists at Stanford University School of Medicine offers insights into cellular ageing and the promise of restoring cognitive functions. Ageing is associated with excess, chronic, low-grade inflammation, a process that specialists refer to as ‘inflammaging’ and believe is involved in many diseases, from Alzheimer’s to cancer. Inflammaging involves changes in the activity and biology of macrophages, specialised cells that detect and destroy bacteria and which form the first line of defence against disease-causing organisms and pathogens. Aged macrophages store energy differently to young and
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June 2021
Ageing is associated with excess, chronic, low-grade inflammation.
healthy ones; for instance, instead of using it for fuel, they save up glycogen to use it in launching a stronger immune response during acute inflammation. But this stronger immune response, an overreaction of sorts, carries a hefty price in the aged brain; it damages normal tissue, tires the immune system, and exacerbates degenerative conditions. Katrin Andreasson, a professor of neurology at Stanford Medicine, is investigating the link between metabolic activity and maladaptive inflammation. In a new study published in Nature, her team showed that microglia—the resident macrophage cells inside our brains—are highly sensitive to changes in the levels of an inflammatory molecule called prostaglandin E2 (PGE2), which they sense via the cell-surface receptor EP2.
Microglia effectively reign over the brain’s active immunity. When they are not busy battling pathogens and suppressing inflammation, they’re clearing the misfolded proteins associated with neurodegeneration,1 removing old or dead neurons and cellular debris, and promoting neurogenesis by protecting and nourishing healthy and youthful neurons. But microglia—as central as they are to brain health—can also accidently turn against the very organ they protect by going into overdrive in response to distress signals that the receptors on their surface pick up. As a result, they end up killing neurons as they try to limit infections or damage.2
Slowing down cognitive decline
The team led by Andreasson used human myeloid cell cultures and aged mouse
