# Methionine Cycle as a Mechanistic Hub for the Hallmarks of Aging

> **NIH NIH R01** · BROWN UNIVERSITY · 2024 · $434,989

## Abstract

Summary (NIH)
Age-dependent changes in Drosophila represent the key Hallmarks of Aging. While the progression of these
Hallmarks is delayed by intervention within the nutrient sensing axis, there is no consensus for how nutrient
sensing mechanistically coordinates Hallmarks or how retarded Hallmarks coordinate to regulate lifespan. We
will address this issue with new genotypes of the Drosophila insulin/IGF receptor (dInr) that differentially affect
nutrient sensing where each extends lifespan. Canonical long-lived dInr mutants are insulin-resistant.
Remarkably, a new dInr mutation within the kinase insert domain (KID) strongly increases lifespan but retains
insulin sensitivity. We conducted RNA, metabolomic and methionine-isotope labeling analyses to gain insight
on how nutrient sensing regulates aging hallmarks. We found insulin-resistant dInr increases cellular methionine
cycle flux, whereas insulin-sensitive dInr decreases this flux. Notably, the methionine cycle is a control hub for
epigenetics, proteostasis, stress resistance, and stem cell regulation – underlying processes of aging hallmarks.
We therefore hypothesize the methionine cycle provides a central mechanism to control multiple Hallmarks of
Aging in response to nutrient sensing. This proposal will establish how nutrient regulation of the methionine cycle
integrates Hallmarks of Aging.

## Key facts

- **NIH application ID:** 10924064
- **Project number:** 5R01AG082801-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Andrey A Parkhitko
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $434,989
- **Award type:** 5
- **Project period:** 2023-09-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10924064

## Citation

> US National Institutes of Health, RePORTER application 10924064, Methionine Cycle as a Mechanistic Hub for the Hallmarks of Aging (5R01AG082801-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10924064. Licensed CC0.

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