# Mitochondrial energetics, exercise intolerance and fatigability in older people with HIV

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $607,859

## Abstract

People living with HIV infection (PLWH) are living longer but with advancing age experience
accelerated functional decline (decreased strength, slowed gait, reduced exercise tolerance) and increased
frailty, as compared to non-infected individuals. The syndromes of functional decline and frailty are associated
with impaired quality of life, increased vulnerability to superimposed stresses, and the likelihood of premature
morbidity and mortality. The mechanisms underlying this accelerated dysfunction and disability, however, are
poorly understood. The proposed project examines the contribution of altered skeletal muscle (SM)
mitochondrial function and high energy phosphate metabolism to the related, but distinct syndromes of fatigue,
exercise intolerance, and frailty often present in older PLWH. Considerable pre-clinical data and our pilot
clinical studies using a 31P magnetic resonance spectroscopy (MRS) fatigability test during and following lower-
extremity exercise suggest an “energetic myopathy” as a possible basis for the fatigue and decreased
performance in older PLWH individuals. However the extent, underlying responsible factors, and functional
significance of altered SM mitochondrial bioenergetics in this population have not been characterized. In
addition, two potential mechanisms responsible for altered SM high energy phosphate metabolism in other
populations, increased inflammation and SM lipid accumulation, have not been examined and related to
muscle energetics in PLWH and so these too will be examined. The central hypothesis is that impaired SM
mitochondrial energy metabolism, initiated by aging and accelerated in the setting of contemporary HIV, is a
central contributor to the geriatric syndromes of fatigue, exercise intolerance, and frailty in older PLWH. We
propose to use state-of-the art 31P MRS exercise testing, detailed muscle and whole body composition
measures, functional assessments during observed and free-living conditions, and biomarkers of inflammation
and immune activation in 200 older (age>=60) women and men derived from four local NIH-sponsored cohorts
to address these questions. The specific aims are 1) to define the scope of SM metabolic changes in older
women and men living with HIV, 2) to probe whether inflammation, skeletal fat and other underlying factors are
related to the energetic abnormalities in older PLWH and 3) to determine the functional significance of SM
energetic changes in older PLWH by examining the relationships between the energetic changes and exercise
tolerance and other functional assessments as well as the frailty phenotype. Fatigue, exercise intolerance, and
frailty are common in older PLWH and the underlying mechanisms remain poorly understood These novel,
timely studies will provide new insights and guide future intervention strategies designed to attenuate or
reverse mitochondrial and bioenergetic decline and thereby reduce the personal and societal toll of these
geriatric conditions in ...

## Key facts

- **NIH application ID:** 9952301
- **Project number:** 5R01AG063661-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ROBERT G WEISS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $607,859
- **Award type:** 5
- **Project period:** 2019-06-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952301

## Citation

> US National Institutes of Health, RePORTER application 9952301, Mitochondrial energetics, exercise intolerance and fatigability in older people with HIV (5R01AG063661-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9952301. Licensed CC0.

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