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University of Pittsburgh Schools of the Health Sciences

New Research Examines Genetics Of Successful Aging

PITTSBURGH, August 10, 2006 — Scientists have identified genes related to reaching age 90 with preserved cognition, according to a study published in the September issue of the
American Journal of Geriatric Psychiatry. The study, which was conducted at the University of Pittsburgh is among the first to identify genetic links to cognitive longevity.

“Successful aging has been defined in many ways, however, we focused on individuals who had reached at least 90 without significant decline in mental capacity,” said lead researcher George S. Zubenko, M.D., Ph.D., professor of psychiatry and biological sciences at the University of Pittsburgh. “While this is a goal that many of us share, such a definition of ‘successful aging’ can be determined objectively and consistently across subjects—an important requirement of scientific studies.”

While previous research has revealed 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 who had 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, who were matched for sex, race, ethnicity and geographic location. Particularly, 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.

The study identified nine genetic regions that were associated with successful aging, 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 majority of the successful aging or “SAG” regions overlapped with gene locations previously reported to show linkage to susceptibility genes for cardiovascular disorders, psychiatric disorders and the accumulation of tissue damage due to oxidative stress. The results of the study also highlighted the detrimental effects of cigarette smoking, excessive drinking and serious mental disorders 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.”

The study was published online ahead of print at http://www.ajgponline.org/ on August 10. The American Journal of Geriatric Psychiatry, published monthly, is the official journal of the American Association for Geriatric Psychiatry.

Co-authors of the paper include Hugh B. Hughes, III, M.D., and Wendy N. Zubenko, Ed.D., A.P.R.N., both of the department of psychiatry, University of Pittsburgh School of Medicine; and Brion S. Maher, Ph.D., of the Center for Craniofacial and Dental Genetics at the University of Pittsburgh School of Dental Medicine.

The study was funded by the National Institute of Mental Health, one of the National Institutes of Health.

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