# Metabolic regulation of healthy aging by diet, mTOR signaling, and skeletal muscle

> **NIH NIH F99** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $9,712

## Abstract

PROJECT SUMMARY
 Obesity, glucose and insulin resistance, and other metabolic disorders are on the rise due in part to the
growing aged population. Dietary interventions such as calorie restriction (CR) can improve and even reverse
these complications but CR diets are difficult for most people to adhere to. Alternative regimens based on
restriction of specific macronutrients, such as protein restriction (PR) or limitation of specific essential amino
acids, have shown promise in improving metabolic health and extend lifespan without needing to limit of
calories.
 I and the Lamming lab have shown that Isoleucine restriction (IleR) improves glucose homeostasis,
improve body weight and adiposity, and even extends the lifespan of mice. IleR induces fibroblast growth
factor 21 (FGF21), an energy expenditure hormone and some but not all of the documented benefits of IleR
are dependent on FGF21. During the F99 phase, I will determine for the first time if FGF21 is required for
lifespan extending effects of IleR by using a mouse model of whole body FGF21 knockout. I will also test the
necessity of mTORC1 in the adipose and skeletal muscle – two key sites of isoleucine catabolism – on IleR
benefits by deleting Raptor specifically in the skeletal muscle or adipose tissue. This study will nicely bridge the
gap between my graduate and postdoctoral work as I shift my focus from whole body metabolism and
physiology to biology of aging muscle.
 In the K00 phase, I will utilize a validated mouse model of resistance exercise training to determine the
interaction between training and the mTORC1 inhibitor rapamycin on skeletal muscle outcomes, such as
muscle mass, fiber type, strength and mitochondrial respiration in both male and female mice of middle and old
age, as well as organismal outcomes including frailty. I will also utilize banked tissues to examine muscular
outcomes in older humans from a randomized clinical trial of everolimus Dr. Konopka has received funding for.
Finally, I will conduct an exploratory analysis of the interaction between skeletal muscle health, everolimus,
and dietary components based on the diet recall collected for each participant in the clinical trial. Completing
these aims will bring me one step closer to my goal of becoming a well-rounded independent researcher
conducting meaningful research on nutrition and metabolism in aging.

## Key facts

- **NIH application ID:** 10936515
- **Project number:** 5F99AG083290-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Michaela Trautman
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $9,712
- **Award type:** 5
- **Project period:** 2023-09-10 → 2024-10-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10936515

## Citation

> US National Institutes of Health, RePORTER application 10936515, Metabolic regulation of healthy aging by diet, mTOR signaling, and skeletal muscle (5F99AG083290-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10936515. Licensed CC0.

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