INVESTIGATING THE ROLE OF SLEEP IN BRAIN RESILIENCE DURING AGING USING A SCALABLE AND SHORT-LIVED VERTEBRAT…

Assistance award details

Assistance award identifier

ASST_NON_R00AG076879_075

FAIN

R00AG076879

Recipient

THE TRUSTEES OF PRINCETON UNIVERSITY

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$249,000

Period

Aug 15, 2023 – Jul 31, 2029

Fiscal year

2026

Place of performance state

NJ

Source file

FY2026_All_Assistance_Full_20261006.zip

Description

INVESTIGATING THE ROLE OF SLEEP IN BRAIN RESILIENCE DURING AGING USING A SCALABLE AND SHORT-LIVED VERTEBRATE MODEL - PROJECT SUMMARY SLEEP IS A CRITICAL BEHAVIORAL STATE THAT FULFILLS ESSENTIAL NEEDS FOR HEALTH, INCLUDING CLEARING WASTE PRODUCTS (E.G., AMYLOID BETA [AΒ]) FROM THE BRAIN. AS HUMANS AGE, SLEEP QUALITY STRIKINGLY DETERIORATES, AND THIS DECLINE CORRELATES WITH INCREASED RISK FOR NEURODEGENERATION, VASCULAR DEMENTIA, AND ALZHEIMER’S DISEASE. WHILE THE OCCURRENCE OF SLEEP DISRUPTION DURING AGING IS WELL DOCUMENTED, THE CAUSATIVE IMPACT OF SLEEP ON BRAIN RESILIENCE WITH AGE AND DISEASE REMAINS UNEXPLORED. I HYPOTHESIZE THAT SLEEP IS A KEY MODULATOR OF ANIMAL HEALTH THAT CAN BE MANIPULATED TO IMPROVE BRAIN RESILIENCE IN THE CONTEXT OF AGING AND DISEASE. TO INVESTIGATE THE IMPACT OF SLEEP ON BRAIN RESILIENCE LATE IN LIFE, I WILL (AIM 1) CHARACTERIZE IF AGE-ASSOCIATED SLEEP DETERIORATION (E.G., CIRCADIAN TIMING AND AMOUNT OF SLEEP) IMPACTS COGNITIVE HEALTH, (AIM 2) PERTURB SLEEP AND TEST THE IMPACT ON COGNITIVE RESILIENCE LATE IN LIFE, AND (AIM 3) DETERMINE IF SLEEP IMPROVES BRAIN RESILIENCE IN THE CONTEXT OF HUMAN AΒ1-42 OVEREXPRESSION. THE AGE DEPENDENCE OF SLEEP DETERIORATION AND NEURODEGENERATION IS DIFFICULT TO STUDY AT SCALE DUE TO THE TIME-CONSUMING CHALLENGE OF AGING VERTEBRATES. TO OVERCOME THIS CHALLENGE AND TACKLE THIS QUESTION, I WILL USE THE AFRICAN KILLIFISH, A MODEL WITH AN EXTREMELY SHORT LIFESPAN OF ONLY 4-7 MONTHS. THE KILLIFISH EXHIBITS KEY HALLMARKS OF HUMAN AGING (E.G., NEURODEGENERATION, FRAILTY) AND HAS CONSERVED BRAIN STRUCTURES AND GENES KNOWN TO REGULATE SLEEP. CRITICALLY, KILLIFISH BRAINS EXHIBIT INCREASES IN NEUROFIBRILLARY DEGENERATION, OXIDATIVE STRESS, GLIOSIS, AND INFLAMMATION, AS WELL AS DECREASES IN REPAIR, AS THEY AGE. THE KILLIFISH ALSO POSSESSES PRACTICAL ADVANTAGES SUCH AS LOW HUSBANDRY COSTS, A SHORT GENERATION TIME (<1 MONTH), AND GENETIC TRACTABILITY. THESE TRAITS MAKE THE KILLIFISH A SUITABLE MODEL SYSTEM TO INVEST