# Studying methionine flux and its role in aging and neurodegeneration

> **NIH NIH R00** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $124,698

## Abstract

Abstract:
Aging is a risk factor for various human pathologies including Alzheimer’s disease, and both aging and
Alzheimer’s disease are characterized by extensive metabolic changes. Several studies have revealed a
number of metabolic pathways for which perturbation of the pathway can extend lifespan in flies and other
organisms. Similarly, Alzheimer’s disease is characterized by extensive metabolic reprogramming. Using
targeted high-throughput metabolite profiling in Drosophila melanogaster adults of different ages, we
demonstrated that methionine metabolism changes during aging. Particularly, we showed that one of the
methionine downstream metabolites, SAH, accumulates with age and further, that inhibition of SAH
accumulation extends life- and healthspan. The experiments proposed in this application aim to address the
fundamental questions of how methionine flux is reprogrammed at the whole-organism level and in different
organs and whether organ-specific activation/suppression of methionine flux can extend lifespan and suppress
different age-related pathological manifestations, including ones associated with Alzheimer’s disease. In
addition, impaired methionine flux and delayed SAH processing may have a strong effect on cellular
physiology via inhibition of a broad spectrum of methyltransferases. I will be using transgenic Drosophila
models relevant to Alzheimer’s disease to analyze how overexpression of human Tau affects methionine flux. I
will be testing the effects of methionine restriction and methyltransferases on pathological signs of
neurodegeneration in control flies and transgenic fly models relevant to Alzheimer’s disease. I will also use a
genetic model of methionine restriction, which will allow me to test the tissue-specific effects of methionine
restriction and examine how the distribution of labeled methionine in downstream metabolic pathways is
changed with age and in fly models relevant to Alzheimer’s disease. Our studies will provide insights into how
restoring of age-dependent defects related to impaired methionine metabolism can be applied to lifespan
extension and to the potential treatment of Alzheimer’s disease.

## Key facts

- **NIH application ID:** 10576497
- **Project number:** 3R00AG057792-05S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Andrey A Parkhitko
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $124,698
- **Award type:** 3
- **Project period:** 2019-02-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10576497

## Citation

> US National Institutes of Health, RePORTER application 10576497, Studying methionine flux and its role in aging and neurodegeneration (3R00AG057792-05S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10576497. Licensed CC0.

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