# DNA methylation markers of Multimorbidity in Aging Humans and Mice

> **NIH NIH K01** · UNIVERSITY OF WASHINGTON · 2022 · $121,392

## Abstract

Multimorbidity (MM), conventionally defined as two or more chronic diseases, is a public health problem
in older adults. MM patients are at high risk of iatrogenesis from polypharmacy, disability, and premature
death, with challenges to caregivers and cost to society. The study of the pathophysiology of MM based on
single biomarkers or pathways has had limited success. Moreover, there are no comprehensive biomarkers
developed to evaluate and predict MM. Previous experience and preliminary data corroborate the hypothesis
of the existence of potential DNA methylation (DNAm) biomarkers that are associated with MM at the
population level. Additionally, the study of mechanisms of MM at the tissue level in humans have been limited
due to ethical and logistical complications. Neglected yet unarguably pivotal, identifying DNAm markers
associated with MM mouse models is of paramount importance to develop our capabilities to predict MM and
shed more light on its underlying mechanisms.
 The overarching goal of this proposal is to identify DNAm markers of MM in human populations and
mouse models to develop a set of comprehensive tools for the identification of at-risk individuals. The resulting
markers will be applicable to both male and female individuals. Using four population cohorts, I will test the use
of DNAm markers to predict who is likely develop MM. I will measure how cell specific DNAm and gene
expression (RNA-seq) are related and different between individuals who are free of MM at baseline and
developed MM and those who remained free of MM. I will use an animal model of MM using histopathology
studies of organs to define mm and measure DNAm and cognate transcriptomics (RNA-seq). The results of
this study can be used to better identify and understand the shared mechanism(s) that causes MM.
Collectively, identifying “DNA methylation markers of multimorbidity in aging humans and mice” should allow
geriatricians to predict multimorbidity in older adults and help researchers to further understand the
mechanisms underlying multimorbidity. The results of this project, in the future, can be applied to test the
effectiveness of interventions such as metformin that target these mechanisms for prevention and treatment of
MM.

## Key facts

- **NIH application ID:** 10551502
- **Project number:** 7K01AG059898-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Shabnam Salimi
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $121,392
- **Award type:** 7
- **Project period:** 2019-05-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10551502

## Citation

> US National Institutes of Health, RePORTER application 10551502, DNA methylation markers of Multimorbidity in Aging Humans and Mice (7K01AG059898-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10551502. Licensed CC0.

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