# Advanced Glycation End-products, Exercise, and Sarcopenia

> **NIH NIH F30** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $35,525

## Abstract

PROJECT SUMMARY / ABSTRACT
The age-related loss of muscle mass, strength, and function, known as sarcopenia, represents one of the five
most common conditions in older adults. Of these five conditions, sarcopenia is the only one for which no FDA-
approved treatment exists. To promote independence and prevent disability in our aging population, the
identification of drug targets for sarcopenia is crucial. The accelerated sarcopenia seen in T2DM is an ideal
model for this purpose, as it is possible to systematically interrogate those pathways that are normally altered
somewhat by the aging process, but are extremely altered by T2DM. By examining these pathways, it may be
possible to identify novel therapeutic targets for sarcopenia. One such pathway, upregulated by the
hyperglycemic milieu of T2DM, is nonenzymatic protein glycosylation and the subsequent formation of AGE.
This detrimental process is known to contribute to multiple disease states. While AGE concentration has
previously been linked to muscle strength and function in cross-sectional studies, and blocking AGE
accumulation in animal models improves muscle mass, the role of AGE in sarcopenia in humans has yet to be
substantiated. We propose that AGE represents a potential mediator of sarcopenia in humans, but more
evidence – specifically, evidence of muscle AGE responsiveness to existing treatment modalities – is required
in humans prior to the conduct of specific clinical trials. To gather this evidence, the present study will examine
subjects with T2DM and healthy older controls before and after 12 weeks of progressive resistance exercise
training. Overall, we hypothesize that progressive resistance exercise training will reduce AGE concentrations
in plasma and muscle, and that these reductions will be associated with improved sarcopenia outcomes –
namely, muscle mass, strength, and function. Furthermore, we will test the hypothesis that progressive
resistance exercise training can be used in patients with T2DM to normalize protein glycosylation and AGE
accumulation, as compared to healthy older controls. Employing clinical, proteomic, biochemical
methodologies, the present study will address this hypothesis through three Specific Aims: 1) identify and
quantify glycated protein targets in aging human muscle and plasma from patients with and without T2DM, 2)
identify the effects of progressive resistance exercise training on protein glycation, AGE concentration, and
downstream effectors of AGE, and 3) determine whether AGE concentration is associated with baseline
differences or intervention-induced changes in measures of muscle mass, strength, or function, and calculate
the percent variation in these measures that is explained by AGE concentration. Determining the impact of
progressive resistance exercise training on protein glycosylation and AGE accumulation will inform the search
for novel therapeutic targets for sarcopenia, and assist in the formulation of future clinical trials.

## Key facts

- **NIH application ID:** 10406776
- **Project number:** 3F30AG058381-04S1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Amanda Randolph
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $35,525
- **Award type:** 3
- **Project period:** 2017-09-15 → 2022-06-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406776

## Citation

> US National Institutes of Health, RePORTER application 10406776, Advanced Glycation End-products, Exercise, and Sarcopenia (3F30AG058381-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10406776. Licensed CC0.

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