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New research examines genetics of successful aging

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 t he 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.

"Historically women have lived longer than men on average, the prevalence of numerous serious diseases differs in men and women, and there are important differences in age-related physiological changes that occur between the sexes over the life span," said Dr. Zubenko. "It would not be surprising if the collection of genes that influences the capacity to reach old age with normal mental capacity differs somewhat for men and women." The results of the study also highlighted the detrimental effects of cigarette smoking and excessive drinking on successful aging in both sexes.

"The finding that genetics, lifestyle decision making, and their interactions, may influence the ability to reach old age with preserved cognition is exciting," stated Dr. Zubenko. "Identifying such genetic and behavioral factors may hold promise for better understanding the aging process and perhaps one day enriching or extending the lives of other individuals."



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