June 11, 2004
Gene Expression Shows Human Brains Age At Different Speeds

Brain genes for learning, stress, repair, inflammation, and immune responses all showed altered responses as we age.

To investigate age-associated molecular changes in the human brain, Dr. Bruce A. Yankner, professor in the Department of Neurology and Division of Neuroscience at Children's Hospital Boston and Harvard Medical School, and colleagues examined patterns of gene expression in postmortem samples collected from thirty individuals ranging in age from 26 to 106 years. Using a sophisticated screening technique called transcriptional profiling that evaluates thousands of genes at a time, the researchers identified two groups of genes with significantly altered expression levels in the brains of older individuals. A gene's expression level is an indicator of whether or not the gene is functioning properly.

"We found that genes that play a role in learning and memory were among those most significantly reduced in the aging human cortex," said Yankner. "These include genes that are required for communication between neurons."

In addition to a reduction in genes important for cognitive function, there was an elevated expression of genes that are associated with stress and repair mechanisms and genes linked to inflammation and immune responses. This is evidence that pathological events may be occurring in the aging brain, possibly related to gene damage.

The researchers then went on to show that many of the genes with altered expression in the brain were badly damaged and could not function properly. They showed that these genes also could be selectively damaged in brain cells grown in the laboratory, thereby mimicking some of the changes of the aging brain.

"Our findings suggest that these genes are unusually vulnerable to damage from agents such as free radicals and toxins in the environment," said Yankner. "The brain's ability to cope with these toxic insults and repair these genes declines with age, leading to their reduced expression. It will now be important to learn how to prevent this damage, and to understand precisely how it impacts brain function in the elderly."

According to Yankner, "If you examine brain gene patterns among young adults, they are quite similar. In very old adults, there is some increased variability, but there is still similarity between individuals. In contrast, individuals in the middle age population between 40 and 70 years of age are much more variable. Some middle-aged individuals exhibit gene patterns that look more like the young group, whereas others show gene patterns that look more like the old group."

This is evidence that people may age differently during middle age. It will now be of great interest to understand what it is that makes some people age more rapidly than others.

These findings raise the exciting possibility that treatments or lifestyles that reduce gene damage in young adults may delay cognitive decline and the onset of brain diseases in later years. However, more research is needed.

"We can repair these aging genes in the laboratory, but that is a far cry from the human brain. This is only a first step," cautions Yankner.

The brain is going to be the hardest organ to repair and rejuvenate. With most organs we are going to be able to just grow replacements or at least replace pieces. But each of your neurons involved in memory or personality encode a part of who you are. Killing off old neurons kills off some small part of who you are. We need to be able to repair individual aged cells. That is going to be hard to do.

The hardest problem is going to be the development of gene therapy techniques for delivering genes into brain cells. The removal of extracellular accumlated junk is probably a more solvable problem as vaccines have already showed considerable promise in removing the beta amyloid plaques involved in Alzheimer's Disease. It is possible that the removal of at least some of the intracellular junk may not turn out to require gene therapy. But my guess is that part of the intracellular junk that accumulates in lysosomes will require gene therapies developed to provide enzymes that can break down that junk.

We need much greater funding and effort aimed at developing brain rejuvenation therapies. We also need a lot more research aimed at discovering why some brains age more rapidly than others. However, it is very likely that just improving blood lipid and cholesterol profiles will reduce the oxidative load on the brain and therefore reduce the rate of brain aging. The sorts of dietary and exercise advice aimed at avoiding heart disease and cancer will very likely slow brain aging as well.

If this report of middle aged signs of brain aging makes the problem more real to you and makes you feel you ought to do something to protect your brain then consider the "ape" diet to improve blood lipids and cholesterol. The ape diet uses a combination of nuts, foods high in soluble fiber (e.g. eggplant), margarines fortified with plant sterols, soy, and vegetables. The ape diet lowers cholesterol, C Reactive Protein (an inflammation indicator), and triglycerides.

There is now a large accumulation of studies which show that cholesterol-lowering statin drugs reduce the risk of Alzheimer's Disease and vascular dementia. Though be aware that some statin drug users experience acute memory problems. Still, you can always stop taking a statin drug or switch to a different one if you experience harmful cognitive effects. But if you are not going to take statins then for the sake of your brain at least consider being like an ape man when you eat and lower your cholesterol that way. Ray Davies had it all figured out years ago when he sang "I'm an ape man, I'm an ape ape man, oh I'm an ape man. I'm a King Kong man, I'm a voodoo man, oh I'm an ape man".

Also see my previous posts Brain Aging Studied With Gene Microarrays, Myelin Cholesterol and Iron Build-Up Leads To Alzheimer's, GABA Neurotransmitter Rejuvenated Aged Monkey Brains, Vitamin C, E In High Dose Combination May Protect Against Alzheimer's.

Share |      Randall Parker, 2004 June 11 03:09 PM  Brain Aging


Comments
Reason said at June 12, 2004 5:22 PM:

I'm thinking that much more basic research is still needed when it comes to genetics and the brain. Paul Allen's brain atlas project is looking timely these days:

http://www.brainatlas.org/

You didn't mention that moderate exercise looks to have beneficial effects on the health of the brain.

http://news.bbc.co.uk/2/hi/health/3492955.stm

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