# Nitrite therapy to improve mitochondrial energetics and physical activity in older adults

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $660,088

## Abstract

Contemporary demographic patterns include the prominent growth of the older adult population. Old age is
associated with declining skeletal muscle mitochondrial bioenergetics, and ramifications include decreased
physical function, increased fatigability, and greater vulnerability to frailty and disability. Therefore, augmenting
mitochondrial respiration may help to fundamentally improve the health and wellbeing of older adults. Our
preliminary data show that inorganic sodium nitrite treatment augments skeletal muscle mitochondrial
bioenergetics in older sedentary adults and that it also enhances the metabolic efficiency of walking (i.e.,
reduced oxygen utilization for the same submaximal walking activity). This provides strong rationale for a 3-
year trial to more definitively analyze the utility of sodium nitrite treatment to enhance skeletal muscle
mitochondrial respiration in older sedentary adults. Nitrites will be administered as convenient capsules, a
novel preparation that we have demonstrated is well-tolerated and associated with high serum nitrite levels.
Aim 1 will emphasize mitochondrial bioenergetic assessments, and include ex vivo (Oroboros) as well as in
vivo (phosphorus magnetic resonance spectroscopy) mitochondrial respirometry measures to fully elucidate
pertinent physiology. Furthermore, skeletal muscle RNA transcription (RNA-seq), Western blots, and
transmission electron microscopy will additional enrich insights regarding nitrite effects on mitochondrial
performance. In Aim 2, complementary vascular analyses will be included, with measures of vascular flow
(flow-mediated dilation) and perfusion (near infrared spectroscopy) to fully delineate nitrite’s endothelial effects.
Aim 3 is exploratory, and focuses on nitrite therapy’s impact on physical function, daily activity, and fatigability.
Physical function is assessed both in terms of physiological measures (i.e., peak oxygen update (VO2) and
VO2 at a submaximal workload) and clinical measures (i.e., endurance [tolerance of submaximal work at 70%
peak VO2 until exhaustion], 6 minute walk distance, the Short Physical Performance Battery, and handgrip
strength). Daily activity is measured using accelerometry. Fatigability is measured in respect to perceived and
performance indices. Overall, this proposal provides a critical mechanistically-oriented perspective regarding
the efficacy of nitrite; if mitochondrial bioenergetics are improved in this analysis, future studies can explore
nitrite’s utility as a therapy to help surmount sedentariness in old age.

## Key facts

- **NIH application ID:** 9873886
- **Project number:** 5R01AG058883-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Daniel E. Forman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $660,088
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873886

## Citation

> US National Institutes of Health, RePORTER application 9873886, Nitrite therapy to improve mitochondrial energetics and physical activity in older adults (5R01AG058883-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9873886. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*