RF1AG092490

MODERATION OF AGING TRAJECTORIES OF COGNITION AND NEUROPATHOLOGY BY DIET COMPOSITION IN MIDDLE-AGED NONHUMAN PRIMATES - PROJECT SUMMARY DIET COMPOSITION POTENTLY MODULATES TRAJECTORIES OF BRAIN AGING. INTAKE OF A MEDITERRANEAN DIET INCLUDING FRUIT AND VEGETABLES, FISH, AND HEALTHY FATS IS ASSOCIATED WITH REDUCED RISK OF ALZHEIMER'S DISEASE AND RELATED DEMENTIAS INCLUDING VASCULAR DEMENTIA. INTAKE OF A WESTERN DIET HIGH IN SIMPLE SUGARS AND SATURATED FAT IS ASSOCIATED WITH INCREASED RISK OF THESE CONDITIONS. NONHUMAN PRIMATE MODELS OF DIET COMPOSITION EFFECTS ON BRAIN HEALTH ARE CRITICAL FOR PROVIDING INSIGHT INTO MECHANISMS OF DIET EFFECTS ON THE BRAIN, BECAUSE OF CHALLENGES ASSOCIATED WITH LONG-TERM STUDIES OF DIET MANIPULATIONS IN HUMANS. OUR PREVIOUS WORK SHOWED WESTERN DIET CONSUMPTION (COMPARED TO MEDITERRANEAN) INCREASED SOCIAL ISOLATION AND ANXIETY-RELATED BEHAVIORS, INCREASED GRAY MATTER VOLUME IN AN ALZHEIMER'S-RELATED TEMPORAL-PARIETAL CORTEX META-REGION OF INTEREST, REDUCED WHITE MATTER VOLUME, AND RESULTED IN LATERAL TEMPORAL TRANSCRIPTIONAL PROFILES ASSOCIATED WITH INFLAMMATION IN MIDDLE- AGED FEMALE CYNOMOGLUS MONKEYS. HOWEVER, BECAUSE COGNITIVE FUNCTION WAS NOT ASSESSED IN THESE MONKEYS, THE INTERPRETATION OF CHANGES IN BIOMARKERS AS REFLECTING A NASCENT PATHOLOGICAL PROCESS OR, ALTERNATIVELY, A RESILIENT ADAPTATION REMAINS UNCLEAR. FOR EXAMPLE, ELEVATED GRAY MATTER VOLUME IN MONKEYS CONSUMING THE WESTERN DIET MAY REFLECT IMPAIRED FUNCTION ASSOCIATED WITH INFLAMMATION, OR A REACTIVE CHANGE TO PRESERVE FUNCTION AND PROMOTE RESILIENCE IN THE FACE OF A POOR DIET. FURTHERMORE, MALES WERE NOT STUDIED IN OUR PREVIOUS WORK. TO ADDRESS THESE CRITICAL BARRIERS TO PROGRESS IN THE FIELD, WE PROPOSE TO TEST THE IMPACT OF MEDITERRANEAN VS. WESTERN DIET ON COGNITIVE FUNCTION AND TRANSLATIONAL IMAGING AND FLUID BIOMARKERS OF ALZHEIMER'S DISEASE RISK, NEUROINFLAMMATION, AND NEURODEGENERATION IN MIDDLE-AGED MALE AND FEMALE CYNOMOLGUS MONKEYS, IN A LONGITUDINAL DESIGN SPANNING 32 MONTHS OF DIET TREATMENT, CORRESPONDING TO ~9.5 HUMAN YEARS. OUR OVERARCHING HYPOTHESIS IS THAT CONSUMPTION OF WESTERN DIET INTERACTS WITH AGING TRAJECTORIES TO EXACERBATE COGNITIVE IMPAIRMENT WITH AGING AND PRODUCE PATHOLOGICAL BRAIN AGING, WHEREAS MEDITERRANEAN DIET PROMOTES RESILIENT AGING, PRESERVED COGNITIVE FUNCTION, AND REDUCTION OF MARKERS OF ALZHEIMER'S DISEASE RISK, INCLUDING FLUID BIOMARKERS OF NEURODEGENERATION AND NEUROINFLAMMATION, AND PET IMAGING MEASURES OF MICROTUBULE STABILITY AND NEUROINFLAMMATION. WE EXPECT THAT WITHIN AND ACROSS DIET TREATMENT GROUPS AND SEXES THAT ELEVATED MARKERS OF NEUROPATHOLOGY WILL PREDICT COGNITIVE DECLINE. THIS PROJECT SPECIFICALLY EXAMINES VULNERABILITY OF MIDDLE-AGED MONKEYS, A TIME IN THE LIFESPAN WHERE TRAJECTORIES OF AGING TAKE A TURN TOWARDS SUCCESSFUL AGING OR GREATER RISK OF NEURODEGENERATIVE DISEASE, WITH IMMENSE TRANSLATIONAL SIGNIFICANCE.

Wake Forest University Health Sciences

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

Winston Salem, North Carolina 27157 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)