Genetic Regions Involved In Brain Aging Rates Identified

A study released today at the American College of Neuropsychopharmacology's Annual Meeting revealed that scientists have identified genes related to reaching age 90 with preserved cognition. The study, which was funded by the National Institutes of Health and conducted at the University of Pittsburgh, is among the first to identify genetic links to cognitive longevity.

"While successful aging has been defined in many ways, we focused on individuals who had reached at least 90 without significant decline in mental capacity," said lead researcher George S. Zubenko, MD, PhD, Professor of Psychiatry and Biological Sciences at the University of Pittsburgh School of Medicine. "Not only is this a goal that many of us share, this definition of 'successful aging' can be determined objectively and consistently across subjects--an important requirement of scientific studies."

While previous research found that genes make important contributions to exceptional longevity, the goal of this study was to identify regions of the human genome that contributed, along with lifestyle factors, to reaching age 90 with preserved cognition.

The study involved 100 people age 90 and older with preserved cognition, as measured by clinical and psychometric assessments. Half of the subjects were male, half were female. Using a novel genome survey method, scientists compared the DNA of the study sample with that of 100 young adults, aged 18-25 years old, who were matched for sex, race, ethnicity and geographic location. Specifically, Dr. Zubenko and his research team attempted to identify specific genetic sequences present in older individuals that may be linked to reaching older ages with preserved cognitive abilities, or conversely, specific genetic sequences present in younger individuals (and not present in those over age 90) that may impede successful aging. The study also looked at a variety of lifestyle factors, such as smoking and alcohol consumption, with the goal of eventually exploring the interactive effects of genes and lifestyle on successful aging.

As expected, the study identified an increased frequency of the APOE E2 allele and a decreased frequency of the APOE E4 allele among the elders compared to the group of young adults. These gene variants confer protection and risk, respectively, of Alzheimer's disease, the most common cause of dementia in late life. The study also identified novel genetic regions associated with successful aging, including DYS389 and DYS390, some of which affected men or women, but not both.

The problem for us is that we already have our versions of genes in our brains. Also, gene therapy is very hard to do and especially hard to do in the brain. However, identification of specific genes that influence aging rate leads to the investigation of mechanisms by which some variants slow or accelerate aging.

Genes that influence brain aging are especially important. Probably in 20 or 30 years time we will be able to grow replacements for all the internal organs. Old parts will be replaced with new parts. But the brain is our identity and needs to be repaired, not replaced. Preferably individual neurons should even be repaired rather than replaced. This makes brain rejuvenation much harder than rejuvenation of the rest of the body. We need to slow brain aging because effective rejuvenation therapies for the brain are going to take longer to develop than rejuvenation therapies for the rest of the body. Also, brain aging has a big economic impact long before we die. Declines in intellectual ability translate into declines in job performance and income.

Even if you are very confident that a cure for aging will be found before you die that is not a reason to be complacent about your diet and lifestyle. Your brain will age and your cognitive abilities will decline while we wait for the realisation of Strategies for Engineered Negligible Senescence (SENS) therapies. Also, a lot of afflictions of middle age and later are no fun at all. Best to delay the onset of assorted maladies as long as you can.

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