# Defining Strategies to Target Energy Failure in Metabolically Vulnerable Human Cells

> **NIH NIH R01** · J. DAVID GLADSTONE INSTITUTES · 2024 · $620,722

## Abstract

Project Summary
Disrupted energy metabolism is a central driver of dysfunction and death in a wide range of diseases, and may
also contribute to aging. Energy failure, or insufficient energy to support normal function, can lead to
neurodegenerative diseases, ischemia and heart failure, while an imbalance in energy production may contribute
to cancer. As such, boosting energy levels has great therapeutic potential to improve cellular function and
survival. However, there are only anecdotal examples of how to increase or preserve cellular ATP levels. To
address this critical unmet need for anti-aging and energy-focused therapeutics, we developed an innovative
high throughput screen that uses a fluorescent biosensor to measure ATP levels in individual cells, and used it
to identify genes and pathways that regulate ATP levels. In this proposal, we will test our central hypothesis
that increasing ATP can enhance the function and survival of vulnerable cells, but the efficacy depends on the
mechanism by which ATP is increased. The overall objectives of our proposed study are to define the most
robust mechanisms to increase cellular energy levels, and to determine if increasing ATP boosts the function
and survival of human cells that are susceptible to diseases of energy failure. We will accomplish these objectives
in two specific aims. (1) We will use metabolomics, transcriptomics and assays of energy production and
consumption to determine the broad mechanisms by which energy levels can be increased. (2) We will determine
if increasing the ATP level can enhance the function and survival of human neurons and cardiomyocytes. Overall,
these studies will i) determine the broad cellular mechanisms by which cellular energy levels can be increased,
and ii) begin to assess the therapeutic potential of increasing energy levels to protect against energy failure in
metabolically vulnerable human cells.

## Key facts

- **NIH application ID:** 10844591
- **Project number:** 5R01AG065428-05
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** KEN NAKAMURA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $620,722
- **Award type:** 5
- **Project period:** 2020-08-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844591

## Citation

> US National Institutes of Health, RePORTER application 10844591, Defining Strategies to Target Energy Failure in Metabolically Vulnerable Human Cells (5R01AG065428-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10844591. Licensed CC0.

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