A decline in cognitive function – reduced attention skills, brain processing speed and reasoning ability – is a normal consequence of aging. For some, the rate of this decline is accelerated and may go on to develop Alzheimer’s disease.

A recent study, published in Nature, shows that the blood of young mice contains proteins that can promote the generation of new brain cells in old mice. If substantiated, it may be possible to slow down or reverse this age-related decline in cognitive function.

Adult neurogenesis, a process in which neural stem cells continue to generate new cells throughout life, overturned the long-held view that the adult brain is incapable of regenerating itself and raised the possibility of developing stem cell-based therapies for neurological conditions such as dementia, stroke and Parkinson’s disease.
Neurogenesis occurs in two regions of the brain: the subventricular zone, generating cells that migrate to the olfactory bulb; and the subgranular zone, producing newborn cells that migrate into the hippocampus, critical for learning and memory formation. Normal age-related cognitive decline may be related to a reduction in the rate at which newborn cells are produced.

Because neural stem cells are located close to blood vessels, neurogenesis may be regulated by chemical cues in the blood. Experiments with mice twins found that pairs of young mice had about the same number of newborn neurons in the dentate gyrus as unpaired mice of the same age. This was also true for pairs of old mice. Remarkably, brains of old mice paired with young mice had many more new cells than unpaired old mice, and those of young mice paired with old ones had much fewer than unpaired young mice. In the adult brain, the only cells containing new DNA are those that have just been produced by the division of neural stem cells.

Chemicals found in the blood of old mice inhibit new brain cell generation, whereas chemicals in the blood of young mice promote it. Researchers then put blood from young or old mice into young adults. Again, they found that animals injected with old blood had far fewer newborn neurons in the hippocampus than those injected with young blood, confirming that old blood contains soluble factors that inhibit neurogenesis.

Investigating the effects of old blood on cell function, researchers took slices of hippocampal tissue from the brains of young mice paired with young and old ones, and using microelectrodes to examine electrical properties, a decrease in long-term potentiation (LTP) was observed. LTP, a form of synaptic plasticity, where connections between neurons are strengthened, is widely believed to be critical for learning and memory.

Speculating that changes in blood composition may be linked to age related cognitive decline, they trained young mice on two different tasks: a fear conditioning task; and a memory task. All of the mice performed similarly on both tasks. After the training, some mice were injected with blood from old mice, and made to perform the same tasks again. The performance of these animals on both tasks worsened.

Finally, researchers compared the proteins found in blood from young and old mice before and after pairing them with animals of the same or a different age. In young mice, the CCL11 protein decreased neurogenesis and impaired performance on the fear conditioning and memory tasks.

These results show that age-related changes in the composition of blood are linked to the decline in adult neurogenesis, suggesting that these rejuvenating factors have the potential to someday alleviate the age related decline in cognitive function.