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Research

Bioenergetics from single organelles to whole humans — the through-line is method. Every question we ask is one we can measure cleanly, repeatedly, and across time.

Research programs

The laboratory's work is organized around four interconnected programs. Each combines a signature measurement, a population of interest, and an open analytic approach.

Skeletal muscle mitochondrial bioenergetics

Substrate–uncoupler–inhibitor titration on Oroboros O2k / NextGen O2k in permeabilized fibers and isolated mitochondria. Coupling, leak, and reserve capacity in aging, obesity, T2D, and cardiometabolic disease.

In vivo NIRS muscle oxidative capacity

Rate constants of muscle reoxygenation (k, min⁻¹) via the Mito-6 paradigm with the Artinis PortaMon MKIII. Method refinement and open analysis via the in-house nirsox R package.

Immunoenergetics

Joint program with the Spielmann Laboratory. PBMC and T-cell bioenergetics before and after acute and chronic exercise; lactate and metabolite regulation of immune cell function.

Translational exercise interventions

Structured exercise trials across the lifespan and across disease. HFpEF, T2D, obesity, cancer survivorship, and healthy aging. Randomized and longitudinal designs.

Ongoing projects

4 active

Selected active studies. The laboratory is currently establishing its research infrastructure at the University of Virginia and welcomes inquiries from prospective collaborators and participants.

REALPA — Resistance Exercise and Low-Intensity Physical Activity Breaks in Sedentary Time to Improve Skeletal Muscle and Cardiometabolic Health in Older Adults

FunderNIH / NIA (R21AG058181)

Principal investigatorBrian A. Irving, PhD, FACSM (PI);
G. Spielmann and N. Johannsen (Co-I)

ParticipantsSedentary older adults (60+)

Research questionCan low-intensity physical-activity breaks combined with resistance training improve skeletal muscle mitochondrial oxidative capacity and cardiometabolic health in sedentary older adults?

MethodsHigh-Resolution Respirometry; DXA body composition; V̇O₂peak; metabolic phenotyping; accelerometry.

Method development for the Oroboros NextGen O2k — mitochondrial respiration and NADH redox balance

FunderLouisiana Board of Regents

InvestigatorsBrian A. Irving, PhD, FACSM (PI);
Ashok Sivasailam, PhD (postdoctoral fellow)

SettingWet-lab · C2C12 myotubes, isolated mitochondria, permeabilized fibers

Research questionCan multi-substrate respirometry protocols be standardized to resolve the "rotenone paradox" and yield reproducible NADH-linked respiration measurements across laboratories?

MethodsHigh-resolution respirometry with fluorometry (NextGen O2k); NADH autofluorescence; SUIT protocol optimization.

Immunoenergetics of exercise — PBMC and T-cell mitochondrial function

FunderContinuing Collaborative Program

InvestigatorsBrian A. Irving, PhD (UVA)
Guillaume Spielmann (LSU)

Research questionHow do exercise-induced changes in circulating metabolites (lactate, ketones) shape T-cell polarization, mitochondrial respiration, and cytotoxic function across the lifespan and in cancer?

Recent outputCho, Spielmann, Irving (2025). Effects of lactate concentration on T-cell phenotype and mitochondrial respiration. Physiol Rep. PMID 40705846.

SWIFT — Surgical Weight-loss to Improve Functional Status Trajectories Following Total Knee Arthroplasty

FunderGeisinger Clinic · Ethicon EndoSurgery

Sub-award PIBrian A. Irving, PhD, FACSM

ParticipantsAdults with severe obesity and advanced knee osteoarthritis

Research questionDoes prior bariatric surgery improve knee-function outcomes compared with immediate total knee arthroplasty among patients with severe obesity and advanced knee osteoarthritis?

ResultsPrimary results published 2026 in the Journal of Arthroplasty by the SWIFT Writing Committee (Benotti, Wood, Irving, et al.). PMID 42184930.

Recent completed projects

Cardiometabolic HFpEF — exercise therapy and nitric oxide / hydrogen sulfide signaling

CollaboratorsAllerton, Lefer, Shah, Ghosh, Noland, Spielmann, Quiriarte

ModelTwo-hit rodent model of heart failure with preserved ejection fraction

FindingsVoluntary exercise rescues skeletal-muscle dysfunction and exercise intolerance in cardiometabolic HFpEF; systemic inflammation is attenuated. An ongoing sub-award examines hydrogen-sulfide donor therapy.

PublicationsQuiriarte et al. (2025) JAHA · Quiriarte et al. (2024) JACC: Basic to Translational Science · Allerton et al. (2024) Sci Rep

Blood-flow-restricted resistance exercise and muscle oxidative capacity

FunderDelfi Medical & institutional pilot support

Research questionDoes low-load resistance exercise with blood-flow restriction improve muscle strength, endurance, and mitochondrial oxidative capacity relative to conventional resistance training?

PublicationsDavis, Spielmann, Johannsen, Irving (2025) Physiol Rep · Davis et al. (2024) Physiol Rep

Impact of exercise modality on skeletal muscle mitochondrial adaptations across age

FunderNIH KL2 Clinical Research Scholar Award (Mayo Clinic)

InvestigatorsBrian A. Irving, PhD (PI); K. S. Nair (mentor)

Research questionDo endurance, resistance, and combined training differentially affect skeletal-muscle mitochondrial oxidative capacity and protein synthesis in young versus older adults?

Key publicationsIrving et al. (2015) J Clin Endocrinol Metab · Konopka et al. (2015) Diabetes

See the full publications record