# Studying methionine flux and its role in aging and neurodegeneration

> **NIH NIH R00** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $248,999

## 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:** 10223531
- **Project number:** 4R00AG057792-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Andrey A Parkhitko
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,999
- **Award type:** 4N
- **Project period:** 2019-02-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10223531

## Citation

> US National Institutes of Health, RePORTER application 10223531, Studying methionine flux and its role in aging and neurodegeneration (4R00AG057792-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10223531. Licensed CC0.

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