Neither intracellular oxygen availability nor mitochondrial coupling explain lower oxidative capacity in older human vastus lateralis muscle in vivo

TY - JOUR

T1 - Neither intracellular oxygen availability nor mitochondrial coupling explain lower oxidative capacity in older human vastus lateralis muscle in vivo

AU - Arieta, Luke R.

AU - Smith, Zoe H.

AU - Nagarajan, Rajakumar

AU - Meyerspeer, Martin

AU - Kent, Jane A.

N1 - Publisher Copyright: © 2026 The Author(s). The Journal of Physiology © 2026 The Physiological Society.

PY - 2026/7/15

Y1 - 2026/7/15

N2 - Abstract: Skeletal muscle oxidative capacity is a useful in vivo marker of mitochondrial health and is generally lower in the knee-extensor muscles of older compared with younger adults. The causes of this lower oxidative capacity in older muscle are unclear. We used magnetic resonance spectroscopy to investigate the influence of intramyocellular oxygen availability and the coupling (P/O ratio) between mitochondrial respiration and ATP production on oxidative capacity in the knee-extensor muscles of 14 young and 10 older adults. Participants completed a 24-s contraction protocol followed by 10 min of recovery and 8 min of cuff occlusion while interleaved 31P and 1H spectroscopy data were acquired. Oxidative capacity was calculated as the rate constant of phosphocreatine recovery, and intramyocellular oxygen tension ((Formula presented.)) was determined from the deoxymyoglobin signal. Critical (Formula presented.), the point at which respiration is limited owing to insufficient oxygen availability, and the P/O ratio were determined for each individual. Oxidative capacity was lower in older than younger muscles, whereas neither critical (Formula presented.) nor the P/O ratio differed between groups. On average, (Formula presented.) remained above the critical (Formula presented.) throughout the protocol in both young and older muscle. Oxidative capacity was modestly related to (Formula presented.) during recovery in young but not older muscle, and mitochondrial coupling was unrelated to oxidative capacity. These novel results do not support a primary role for limited oxygen availability or impaired mitochondrial coupling in the lower oxidative capacity of older knee-extensor muscles and suggest instead that other mechanisms, such as lower mitochondrial content, might be responsible. (Figure presented.). Key points: Knee-extensor muscle oxidative capacity is generally lower in older age, but the questions of whether this decline is attributable, in part, to insufficient oxygen availability or altered coupling between mitochondrial energy production and oxygen consumption remain open. Interleaved 31P and 1H magnetic resonance spectroscopy was used to measure intramyocellular phosphocreatine and deoxygenated myoglobin in vivo, respectively, in the knee-extensor muscles of young and older adults in response to a 24-s contraction protocol and 8 min of circulatory occlusion. Oxidative capacity was indeed lower in the older muscles, but intracellular oxygen availability during and after contractions was sufficient to support oxidative metabolism and did not differ in young and older muscles. Mitochondrial coupling did not differ by age and was unrelated to oxidative capacity. Thus, the lower knee-extensor muscle oxidative capacity in older age is not a result of inadequate intramyocellular oxygen availability or differences in mitochondrial coupling.

AB - Abstract: Skeletal muscle oxidative capacity is a useful in vivo marker of mitochondrial health and is generally lower in the knee-extensor muscles of older compared with younger adults. The causes of this lower oxidative capacity in older muscle are unclear. We used magnetic resonance spectroscopy to investigate the influence of intramyocellular oxygen availability and the coupling (P/O ratio) between mitochondrial respiration and ATP production on oxidative capacity in the knee-extensor muscles of 14 young and 10 older adults. Participants completed a 24-s contraction protocol followed by 10 min of recovery and 8 min of cuff occlusion while interleaved 31P and 1H spectroscopy data were acquired. Oxidative capacity was calculated as the rate constant of phosphocreatine recovery, and intramyocellular oxygen tension ((Formula presented.)) was determined from the deoxymyoglobin signal. Critical (Formula presented.), the point at which respiration is limited owing to insufficient oxygen availability, and the P/O ratio were determined for each individual. Oxidative capacity was lower in older than younger muscles, whereas neither critical (Formula presented.) nor the P/O ratio differed between groups. On average, (Formula presented.) remained above the critical (Formula presented.) throughout the protocol in both young and older muscle. Oxidative capacity was modestly related to (Formula presented.) during recovery in young but not older muscle, and mitochondrial coupling was unrelated to oxidative capacity. These novel results do not support a primary role for limited oxygen availability or impaired mitochondrial coupling in the lower oxidative capacity of older knee-extensor muscles and suggest instead that other mechanisms, such as lower mitochondrial content, might be responsible. (Figure presented.). Key points: Knee-extensor muscle oxidative capacity is generally lower in older age, but the questions of whether this decline is attributable, in part, to insufficient oxygen availability or altered coupling between mitochondrial energy production and oxygen consumption remain open. Interleaved 31P and 1H magnetic resonance spectroscopy was used to measure intramyocellular phosphocreatine and deoxygenated myoglobin in vivo, respectively, in the knee-extensor muscles of young and older adults in response to a 24-s contraction protocol and 8 min of circulatory occlusion. Oxidative capacity was indeed lower in the older muscles, but intracellular oxygen availability during and after contractions was sufficient to support oxidative metabolism and did not differ in young and older muscles. Mitochondrial coupling did not differ by age and was unrelated to oxidative capacity. Thus, the lower knee-extensor muscle oxidative capacity in older age is not a result of inadequate intramyocellular oxygen availability or differences in mitochondrial coupling.

KW - Atp

KW - P/O ratio

KW - Ageing

KW - Cellular respiration

KW - Deoxymyoglobin

KW - Intracellular oxygen tension

KW - Knee extensors

KW - Phosphocreatine recovery

UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=meduni_vienna_pure&SrcAuth=WosAPI&KeyUT=WOS:001781582300001&DestLinkType=FullRecord&DestApp=WOS_CPL

U2 - 10.1113/JP291176

DO - 10.1113/JP291176

M3 - Article

C2 - 42227731

SN - 0022-3751

VL - 604

SP - 6009

EP - 6027

JO - Journal of Physiology

JF - Journal of Physiology

IS - 14

ER -