Exercise to maintain a healthy brain while aging

Structural deterioration of the brain associated with old age can be eased by long-term aerobic exercise starting in mid-life, according to research published in PLOS Biology.

Exercise from middle age can help prevent dementia later in life.

Frailty and cognitive decline tend to accompany aging, and exercise is known to combat them. How this works is not completely understood, but the development of dementias such as Alzheimer's disease has been linked with physical inactivity.

The risk of dementia increases with age. Age-related cognitive deficits result partly from changes in neuronal function, but also correlate with deficiencies in the blood supply to the brain and with low-level inflammation.

The researchers from The Jackson Laboratory in Bar Harbor, ME, found that structural changes that make the blood-brain barrier leaky, causing inflammation of brain tissues in old mice, can be reduced by allowing the animals to run regularly.

The researchers started by investigating changes in the brains of normal young and aged laboratory mice by comparing by their gene expression profiles using RNA sequencing, and by comparing their structures at high-resolution by using fluorescence microscopy and electron microscopy.

What normal aging looks like

The research team found age-related changes in the expression of genes relevant to vascular function and inflammation in the brain cortex.

There was a decline in the function of astrocytes, key support cells in the brain; a loss of pericytes, which surround small capillaries and venules and maintain the blood-brain barrier; and a loss of major components of the basement membrane, which forms an integral part of the barrier.

An increase also occurred in the density and activity of immune cells known as microglia/monocytes, which scavenge the brain for infectious agents and damaged cells.

Evidently, normal aging causes significant dysfunction to the cortical neurovascular unit and an increase in immune activity in the aged cortex.

How exercise can make a difference

Physical activity is known to reduce age-related cognitive decline and sensorimotor deficits in both humans and mice.

To investigate the impact of long-term physical exercise on brain changes, the researchers provided mice with a running wheel from 12 months old - equivalent to middle age in humans. They assessed their brains at 18 months, equivalent to around 60 years in humans, the age at which the risk of Alzheimer's increases.

Both young and old mice ran about 2 miles each night; 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.

Tests showed that age-related pericyte loss in the brain cortex was significantly reduced in these mice, and other indicators of dysfunction of the vascular system and blood-brain barrier were improved. The numbers of microglia/monocytes also decreased.

Aerobic exercise from middle to older age appears to preserve cerebrovascular health, prevent behavioral deficits and reduce age-related neuroinflammation in the cortex and hippocampus in aged mice.

Interestingly, mice which were deficient in a gene called Apoe, a risk factor for Alzheimer's, did not benefit from this exercise. Apoe expression in the brain cortex was seen to decline in aged mice; researchers report that this decline can also be prevented by exercise.

The researchers recommend focusing future efforts on understanding the impact of aging and lifestyle choices on neurovascular unit decline and neuroinflammation, particularly astrocyte and pericyte dysfunction.

"As a society we need to work hard to ensure we maintain an active lifestyle wherever possible. In this day and age, with so many distractions and conveniences, it is easy to fall into a lifestyle that does not include enough exercise. With an aging population, I hope our study helps in encouraging a healthy lifestyle that includes exercise."

The research team believes that understanding the biological changes that trigger cognitive deterioration during aging and the mechanisms by which exercise improves health and brain function is key to ensuring quality of life for elderly people, and to reducing risk of dementias such as Alzheimer's disease. 

References:

1.  APOE stabilization by exercise prevents aging neurovascular dysfunction and complement induction, Ileana Soto et al., PLOS Biology, doi:10.1371/ journal.pbio.1002279, published 29 October 2015.
2.  PLOS news release, accessed 27 October 2015.