Thursday, February 04, 2021

A Tweak to Immune Cells Reverses Aging in Mice

Good news! Towards a cure for Alzheimer's disease in the next 5-15 years! Research is turning from many years of painstaking analysis to targeted intervention!

"... that deleting the EP2 receptor in mouse macrophages and brain-specific microglia ... reduces inflammation and increases neuronal survival in response to both a bacterial toxin and a neurotoxin. ...
The cells from older [blood] donors made much more PGE2 and had higher abundance of the EP2 receptor than did macrophages from younger donors. When the researchers exposed human macrophages to PGE2, the cells altered their metabolism. Rather than using glucose to make energy, the cells converted it to glycogen and stored it, locking it up where the mitochondria couldn’t access it for ATP production. ..."

"Ageing is characterized by the development of persistent pro-inflammatory responses that contribute to atherosclerosis, metabolic syndrome, cancer and frailty ... Systemically, circulating pro-inflammatory factors can promote cognitive decline, and in the brain, microglia lose the ability to clear misfolded proteins that are associated with neurodegeneration ...
In ageing macrophages and microglia, PGE2 signalling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. This energy-deficient state, which drives maladaptive pro-inflammatory responses, is further augmented by a dependence of aged myeloid cells on glucose as a principal fuel source. In aged mice, inhibition of myeloid EP2 signalling rejuvenates cellular bioenergetics, systemic and brain inflammatory states, hippocampal synaptic plasticity and spatial memory. Moreover, blockade of peripheral myeloid EP2 signalling is sufficient to restore cognition in aged mice. ..."

A Tweak to Immune Cells Reverses Aging in Mice | The Scientist Magazine® Knocking out the receptor for a lipid that causes inflammation rejuvenates macrophage metabolism and restores cognitive function in an Alzheimer’s disease model.

Here is the link to the underlying research paper:

There is even a very long commentary published by Nature on this paper:
Reversal of immune-cell shutdown protects the ageing brain Immune cells called macrophages have been found to shut down major metabolic pathways during ageing. Restoring metabolism in these cells is sufficient to alleviate age-associated cognitive decline in mice.

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