# Does Metformin Modulate the Pillars of Aging in Older Adults?

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $410,523

## Abstract

Based upon epidemiological data and interventional studies in invertebrates and rodents, metformin is a
leading candidate to modulate aging. Yet, these animal studies have limited applicability to human subjects
because they usually are of short duration and apply metformin doses that are much higher than the doses used
in humans. Thus, the impact that metformin has on aging-focused outcomes and the mechanism by
which metformin may promote healthy life extension in older human subjects is unknown.
 This grant application targets RFA-AG-20-044 “The Biological Mechanisms of Metformin Effects on Aging
and Longevity” to test the hypothesis that metformin modulates critical pillars of aging in older adults to improve
healthspan. We will leverage our ongoing NIA-funded randomized, placebo-controlled trial of metformin to
prevent frailty in older adults (R01AG052697). The parent trial (n=120) is testing whether metformin
administration for 24 months can prevent or delay the onset of frailty in older (≥ 65 years) adults. Deep aging-
focused phenotyping includes changes in frailty (Fried phenotype score and Rockwood deficit accumulation
index), physical function (short physical performance battery and 6-minute walk), muscle strength/mass, glucose
metabolism (insulin clamping and glucose tolerance) and cognition (Mini-Mental State Exam). The parent trial
also collects several biospecimens including blood, skeletal muscle and adipose tissue before and during
metformin/placebo administration for measures of metabolic (AMPK and insulin signaling) and inflammation
(NFκB and MAPKs) pathways.
 By applying innovative metabolomic, proteomic, molecular and biostatistical methodologies we will take
advantage of these rich phenotypic data and biospecimens to evaluate the effect of metformin on 1)
mitochondrial function; 2) cellular senescence; 3) epigenetics (DNA methylation), which will be in addition to the
pillars of aging studied in the parent grant (metabolism and inflammation). Our objectives are:
Aim 1) To determine the effect of metformin on pillars of aging in older adults.
Aim 2) To determine the link between metformin-induced modifications in pillars of aging and changes
in aging-focused phenotypic outcomes.
 We have assembled an interdisciplinary group across three institutions (UTHSCSA, Mayo, UCLA) that is well
poised to help clarify the molecular and cellular mechanisms by which metformin promotes healthy life extension.

## Key facts

- **NIH application ID:** 10087333
- **Project number:** 1R01AG069690-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Sara Elyse Espinoza
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $410,523
- **Award type:** 1
- **Project period:** 2020-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087333

## Citation

> US National Institutes of Health, RePORTER application 10087333, Does Metformin Modulate the Pillars of Aging in Older Adults? (1R01AG069690-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10087333. Licensed CC0.

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