THOMAS DEERINCK, NCMIR/SCIENCE PHOTO LIBRARY
Wiping out zombie-like brain cells that are worn out but won’t kill themselves could provide a new way to prevent or treat Alzheimer’s disease and other types of dementia. That’s the conclusion of experiments in mice showing that if these ‘senescent’ cells are eradicated as they develop through life, the brain is protected against further degeneration.
“We show that senescent cells promote neurodegeneration and cognitive loss,” says Darren Baker of the Mayo Clinic in Rochester, Minnesota, and head of the team. “Preventing these cells from accumulating attenuates disease.”
Baker studied mice genetically engineered so that their brains degenerate unusually early in life by becoming clogged with damaging clumps of fibres called tau tangles. His team discovered that by the time the mice were a year old, they had also over-accumulated senescent cells. Compared with healthy control mice, they had a dozen times as many senescent cells in the brain’s memory centre – the hippocampus – and twice as many in the cortex, the “thinking” hub of the brain.
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Cell destroyer
To find out if senescent cells also drive the tau-related brain degeneration, the researchers crossed the tau tangle-prone mice with mice whose senescent cells could be selectively destroyed as they emerged throughout life by treating the mice with a drug called AP. Destroying the senescent cells halted brain degeneration in the tau tangle-prone mice, and prevented their usual loss of memory and cognitive ability.
“This is exciting,” says Aubrey de Grey, a co-founder of the SENS Research Foundation in Mountain View, California. “Several years of work pioneered by Baker and his colleagues has shown overwhelmingly that senescent cells make far broader contributions to the health problems of old age than we might previously have expected.”
Earlier this year, another team at Mayo showed they could increase by 36 per cent the lifespan of elderly mice by giving them a drug combination – including one derived from apple peel – that destroys senescent cells.
Journal reference: Nature, DOI: 10.1038/s41586-018-0543-y
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