Does Lower Oxidative Capacity Influence the Relative Contributions of ATP-Producing Pathways During Muscular Work in Aging?

Zoe H Smith; Liam F Fitzgerald; Rajakumar Nagarajan; Kate L Hayes; Martin Meyerspeer; Alfredo L Lopez Kolkovsky; Jane A Kent

doi:10.1093/gerona/glaf142

Does Lower Oxidative Capacity Influence the Relative Contributions of ATP-Producing Pathways During Muscular Work in Aging?

J Gerontol A Biol Sci Med Sci. 2025 Jul 2:glaf142. doi: 10.1093/gerona/glaf142. Online ahead of print.

Authors

Zoe H Smith¹, Liam F Fitzgerald¹, Rajakumar Nagarajan², Kate L Hayes¹, Martin Meyerspeer³, Alfredo L Lopez Kolkovsky^{4

5}, Jane A Kent¹

Affiliations

¹ Muscle Physiology Laboratory, Department of Kinesiology, University of Massachusetts Amherst, MA, USA.
² Human Magnetic Resonance Center, Institute for Applied Life Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
³ Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
⁴ NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France.
⁵ CEA, NeuroSpin, CNRS, Université Paris.

PMID: 40600907
DOI: 10.1093/gerona/glaf142

Abstract

Although the capacity of skeletal muscle to produce ATP via oxidative phosphorylation may decrease in some muscles in older age, the influence of a lower capacity on relative use of oxidative and non-oxidative ATP production pathways in vivo during contractions is unclear. To test the hypothesis that lower oxidative capacity would yield greater non-oxidative ATP production, 19 young (10F) and 17 older (9F) adults performed knee extensor muscle contractions in a 3-tesla magnetic resonance system. Phosphorus metabolites were used to calculate oxidative capacity (rate constant of phosphocreatine recovery; k PCr, s-1) and estimate the maximal rate of oxidative ATP production (Vmax, mM·s-1) following a 24-s dynamic contraction protocol. Next, ATP production (mM·s-1) by the creatine kinase reaction (ATPCK), glycolysis (ATPGLY), and oxidative phosphorylation (ATPOX) was determined during 4 min of dynamic muscle contractions. Proton spectroscopy of deoxymyoglobin was also acquired in a subset (n = 12) and used to calculate the cytosolic partial pressure of oxygen (PO2). Young muscle had a greater k PCr (0.023±0.005s-1, mean±SD) than older muscle (0.020±0.003s-1, p = 0.033). ATPCK, ATPGLY, and ATPOX were not different by group (p ≥ 0.129), but ATPOX as %Vmax was lower in younger than older muscle (55±14%, 71±10%, respectively, p < 0.001). Intracellular oxygen availability (PO2) was not different by group (young: 2.4±0.7 Torr, n = 7; older: 3.2±1.6 Torr, n = 5, p = 0.371). These new findings suggest a bioenergetic rigidity in older muscle, such that it adapts to the energetic demand by using oxidative ATP production at a greater percentage of capacity rather than switching to an increased use of non-oxidative ATP production.

Keywords: biochemistry; fatigue; glycolysis; mitochondria; muscles.

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