# Metabolomic profile of chronic distress in relation to diseases of aging across diverse populations

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2024 · $789,995

## Abstract

Various forms of chronic distress have been linked with premature aging, and development of cardiometabolic
diseases (CMD), which are leading causes of death for older adults. Both chronic distress and CMD conditions
are strongly linked with risk of Alzheimer's Disease and Alzheimer's Disease-Related Dementias (AD/ADRD).
While metabolic changes affecting vascular health are proposed as a key pathway driving the relationship
between chronic distress and major diseases of aging, understanding of molecular mechanisms underlying
such metabolic changes is limited. High-throughput technologies permit simultaneous measurement of
hundreds of metabolites in plasma (“metabolomics”) and provide a broad picture of an individual’s metabolic
profile. In our first funding cycle, we developed and validated a liquid chromatography-tandem mass
spectrometry (LC-MS)-based metabolomic score of chronic distress (anxiety and depression), in independent
data sets of largely non-Hispanic White women; this score was associated with higher risk of incident CMD. In
this renewal, using cutting edge metabolomic and biostatistical approaches along with several additional cohort
studies, we propose to extend our initial findings and address the following specific aims: (1) Strengthen our
existing chronic distress metabolite-score by adding novel, previously unknown metabolites strongly
associated with the distress phenotype, and biochemically identify these validated but unknown metabolites to
provide new mechanistic insight; (2) Assess our chronic distress metabolomic score (and its components) in
key populations including African-American (AA) and Hispanic men and women and White men, and optimize
the score in each population. We will also evaluate associations of the score (and components) with CMD and
secondarily AD/ADRD risk in AA men and women, White men, and preliminarily in Hispanic men and women,
and (3) Evaluate if chronic distress influences the distress-related metabolite score using causal methods and
evaluate the distress-metabolite score as a potential mediator of the relationships of chronic distress with CMD
risk and secondarily with AD/ADRD risk. We will achieve our aims by leveraging the robust data resources of
five prospective studies: the Jackson Heart Study (n=5,306; 100% AA men and women), the Multi-Ethnic
Study of Atherosclerosis (n=6,814; 39% White, 28% AA, 22% Hispanic, 12% Asian-American men and
women), the Nurses’ Health Study (NHS; n=121,700, 98% White women), the Women’s Health Initiative
(n=161,808 women; 18% non-White), PREDIMED (n=7,447; White men and women). Each cohort has
similarly assessed chronic distress, blood metabolomic profiles, relevant covariates, CMD and dementia risk
outcomes over up to 20 years of follow-up. NHS and MESA also have genetics data and repeated
metabolomics measures. This work will extend our understanding of biologic pathways underlying chronic
distress and their association with subsequent CMD and dementia risk amo...

## Key facts

- **NIH application ID:** 10748414
- **Project number:** 5R01AG051600-06
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Susan E Hankinson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $789,995
- **Award type:** 5
- **Project period:** 2017-09-15 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10748414

## Citation

> US National Institutes of Health, RePORTER application 10748414, Metabolomic profile of chronic distress in relation to diseases of aging across diverse populations (5R01AG051600-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10748414. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*