Long-term exercise prevents age-related brain changes

A study of the brains of mice shows that deterioration associated with old age can be prevented by long-term aerobic exercise starting in mid-life.


The findings are according to the authors of a research article publishing in the Open Access journal PLOS Biology on 29 October 2015.


Gareth Howell, Ileana Soto and their colleagues at The Jackson Laboratory in Bar Harbor, Maine (USA) found that structural changes that make the blood–brain barrier leaky and result in inflammation of brain tissues in old mice can be mitigated by allowing the animals to run regularly, so providing a potential explanation for the beneficial effects of exercise on dementia in humans.

Old age is the major risk factor for Alzheimer's disease, like many other diseases.


Age-related cognitive deficits are due partly to changes in neuronal function, but also correlate with deficiencies in the blood supply to the brain and with low-level inflammation.


The authors set out to investigate the changes in the brains of normal young and aged laboratory mice by comparing by their gene expression profiles using a technique called RNA sequencing, and by comparing their structures.


The gene expression analysis indicated age-related changes in the expression of genes relevant to vascular function, and inflammation (especially related to the complement system, which clears foreign particles) in the brain cortex.


These changes were accompanied by a decline in the function of astrocytes (key support cells in brain) and loss of pericytes (the contractile cells that surround small capillaries and venules and maintain the blood–brain barrier) and of major components of the basement membrane, which forms an integral part of the blood–brain barrier, as well as an increase in the density and functional activation of the immune cells known as microglia/monocytes, which scavenge the brain for infectious agents and damaged cells.


Dr. Soto, lead author on the study, says: "Collectively, our data suggests that normal aging causes significant dysfunction to the cortical neurovascular unit, including basement membrane reduction and pericyte loss. These changes correlate strongly with an increase in microglia/monocytes in the aged cortex.”


Physical activity is already known to ameliorate the cognitive decline and sensorimotor deficits seen in old age in humans as well as in mice.


To investigate the impact of long-term physical exercise on the brain changes seen in the aging mice, the researchers provided the animals with a running wheel from 12 months old (equivalent to middle aged in humans) and assessed their brains at 18 months (equivalent to ~60yrs old in humans, when the risk of Alzheimer's disease is greatly increased).


Young and old mice alike ran about two miles per night, and this physical activity improved the ability and motivation of the old mice to engage in the typical spontaneous behaviors that seem to be affected by aging.


This exercise significantly reduced age-related pericyte loss in the brain cortex and improved other indicators of dysfunction of the vascular system and blood–brain barrier.


Exercise also decreased the numbers of microglia/monocytes expressing a crucial initiating component of the complement pathway that others have shown previously to play are role in age-related cognitive decline.


Interestingly, these beneficial effects of exercise were not seen in mice deficient in a gene called Apoe, variants of which are a major genetic risk factor for Alzheimer's disease. The authors also report that Apoe expression in the brain cortex declines in aged mice and this decline can also be prevented by exercise.


Previous studies showing that exercise is beneficial for the human brain suggest the effects on mice are relevant for human health.

See the open access article "APOE Stabilization by Exercise Prevents Aging Neurovascular Dysfunction and Complement Induction" in PLOS Biology.


29 October 2015.