A MULTI-OMIC AND INTEGRATIVE LONGITUDINAL EVALUATION OF THE ROLE OF LIPID, ANTIOXIDANT, AND OSMOPROTECTANT…

Assistance award details

Assistance award identifier

ASST_NON_R00AG081495_075

FAIN

R00AG081495

Recipient

THE MCLAUGHLIN RESEARCH INSTITUTE FOR BIOMEDICAL SCIENCES, INC.

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$244,811

Period

Jul 15, 2023 – Jan 31, 2029

Fiscal year

2026

Place of performance state

MT

Source file

FY2026_All_Assistance_Full_20261006.zip

Description

A MULTI-OMIC AND INTEGRATIVE LONGITUDINAL EVALUATION OF THE ROLE OF LIPID, ANTIOXIDANT, AND OSMOPROTECTANT METABOLITES IN THE GENITOURINARY SYNDROME OF MENOPAUSE BY RACE AND ETHNICITY. - THE GENITOURINARY SYNDROME OF MENOPAUSE (GSM) IS AN AGE-RELATED CHRONIC, PROGRESSIVE UROGENITAL CONDITION THAT DISPROPORTIONATELY AFFECTS POSTMENOPAUSAL WOMEN AND CONTRIBUTES >$3 BILLION ANNUALLY TO US HEALTHCARE COSTS. THE IMPACT OF GSM IS EXTENSIVE AND AFFECTS >62 MILLION US WOMEN. RACIAL AND ETHNIC MINORITIES ARE DISPROPORTIONATELY AFFECTED BUT REMAIN UNDERREPRESENTED IN AGING AND SEXUAL HEALTH RELATED STUDIES. THE VAGINAL MICROBIOTA IS A CRITICAL DETERMINANT IN UROGENITAL AND SEXUAL HEALTH, AND WE HYPOTHESIZE THIS RELATIONSHIP MAY BE MEDIATED THROUGH HOST-MICROBIAL METABOLITE INTERACTIONS. AS WOMEN AGE, ESTROGEN LEVELS DECLINE DISRUPTING ESTROGEN-DEPENDENT PROCESSES. IN A LARGE COHORT (N=1190), I OBSERVED CHRONOLOGICAL AGING TO BE ASSOCIATED WITH ALTERED LIPID METABOLISM (E.G., LIPID PEROXIDATION), LOSS OF PROTECTIVE VAGINAL LACTOBACILLI, CELLULAR DAMAGE (E.G., INCREASED OXIDATIVE STRESS METABOLITES), AND A DECLINE IN VAGINAL ANTIOXIDANTS (E.G., VITAMINS). OXIDATIVE STRESS INDUCES INFLAMMATION, AND BIOMARKERS OF OXIDATIVE STRESS WITHIN SERUM AND PLASMA HAVE BEEN LINKED TO AGE- RELATED PATHOLOGIES (E.G., OSTEOPOROSIS, CARDIOVASCULAR DISEASE, AND ALZHEIMER’S DISEASE). SOME ANTIOXIDANTS CAN BE PRODUCED BY THE HOST (E.G., GLUTATHIONE), WHILE OTHERS MUST BE OBTAINED THROUGH THE DIET AND MICROBIOTA (E.G., VITAMINS). ANTIOXIDANTS SERVE TO NEUTRALIZE OXIDATIVE AND OSMOTIC STRESS AND THEIR DECLINE INCREASES SUSCEPTIBILITY TO OXIDATIVE STRESS RELATED PATHOLOGIES. THIS HAS NOT BEEN YET DESCRIBED WITHIN THE VAGINA. THE K99 PHASE PROPOSES TO (1) CHARACTERIZE THE RELATION OF VAGINAL LAO PROFILES WITH REPRODUCTIVE STAGE, CHRONOLOGICAL AGE, AND RACE/ETHNICITY; AND (2) QUANTIFY THE LONGITUDINAL MEDIATION BETWEEN LAO PROFILES AND GSM BY COMBINING MACHINE LEARNING, STRUCTURAL MODELS, AND MULTI-O