Worn-out cells eventually stop dividing


CELLS divide many times throughout their lives. But they cannot do it indefinitely. Once they have reached the limits of their reproductive powers, they enter a state called “senescence”, in which they carry on performing their duties but stop making new copies of themselves. For years it was assumed that, apart from their refusal to divide, senescent cells were otherwise identical to their replicating compatriots.

There is mounting evidence, though, that this is untrue. One study in 2016 reported that senescent cells in the kidneys and heart produce a protein that causes nearby healthy tissues to deteriorate. Another study found that senescent cells contribute to diseases like atherosclerosis and arthritis. New work led by Darren Baker, a biologist at the Mayo Clinic in Minnesota, published in Nature this week, suggests the accumulation of senescent cells within the brains of mice causes the animals to develop neurodegenerative diseases—and that clearing out these cells can help prevent them.

Working with a team of colleagues, Dr Baker obtained a population of mice that had been genetically engineered to quickly develop fibrous tangles of protein in their brains. These tangles are associated with the decline in mental abilities caused by diseases like Alzheimer’s. When the mice were four months old, Dr Baker collected brain tissue from some, and found senescent cells accumulating in the hippocampus, a seahorse-shaped region of the brain involved with learning and memory. By six months old, they were accumulating in the cerebral cortex as well—as were the tangles that are associated with neurological degeneration.

To see what role, if any, senescent cells were playing in the their diminishing brainpower, Dr Baker genetically altered some mice such that their senescent cells could be eliminated with a twice-weekly dose of a specific chemical. That left a subgroup of mice that were still genetically predisposed to neurological diseases, but which also had their brains rinsed of senescent cells.

By the time these mice reached six months old, the tangles were almost entirely absent. When the mice were presented with objects they had encountered before, they approached them without hesitation, as healthy mice should. In contrast, mice whose brains were full of senescent cells approached the objects tentatively, as if they had never seen them before.

Mice are not people. It remains to be seen whether clearing exhausted cells from human brains could have similar benefits. Since it is not possible to do pre-emptive genetic engineering on humans, some pharmaceutical method of clearing out senescent cells will have to be developed instead. But Dr Baker’s results suggest that is worth trying. Indeed, the next project in his lab is to explore whether clearing senescent cells from the brains of mice that are already suffering from the murine version of Alzheimer’s might allow their already damaged brains to recover.