Adam J Santanasto1, Nancy W Glynn2, Sharon A Jubrias3, Kevin E Conley3, Robert M Boudreau1, Francesca Amati4, Dawn C Mackey5, Eleanor M Simonsick6, Elsa S Strotmeyer1, Paul M Coen7, Bret H Goodpaster8, Anne B Newman1. 1. Department of Epidemiology, Center for Aging and Population Health, Graduate School of Public Health, University of Pittsburgh, Pennsylvania. 2. Department of Epidemiology, Center for Aging and Population Health, Graduate School of Public Health, University of Pittsburgh, Pennsylvania. glynnn@edc.pitt.edu. 3. Translational Center for Metabolic Imaging, University of Washington, Seattle. 4. Division of Endocrinology and Metabolism, School of Medicine, University of Pittsburgh, Pennsylvania. 5. Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, Canada. 6. Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland. 7. Division of Endocrinology and Metabolism, School of Medicine, University of Pittsburgh, Pennsylvania. Department of Health and Physical Activity, School of Education, University of Pittsburgh, Pennsylvania. Present address: Florida Hospital-Sanford|Burnham Translational Research Institute for Metabolism and Diabetes, Orlando. 8. Division of Endocrinology and Metabolism, School of Medicine, University of Pittsburgh, Pennsylvania. Present address: Florida Hospital-Sanford|Burnham Translational Research Institute for Metabolism and Diabetes, Orlando.
Abstract
BACKGROUND: Fatigability increases while the capacity for mitochondrial energy production tends to decrease significantly with age. Thus, diminished mitochondrial function may contribute to higher levels of fatigability in older adults. METHODS: The relationship between fatigability and skeletal muscle mitochondrial function was examined in 30 participants aged 78.5 ± 5.0 years (47% female, 93% white), with a body mass index of 25.9 ± 2.7 kg/m(2) and usual gait-speed of 1.2 ± 0.2 m/s. Fatigability was defined using rating of perceived exertion (6-20 point Borg scale) after a 5-minute treadmill walk at 0.72 m/s. Phosphocreatine recovery in the quadriceps was measured using (31)P magnetic resonance spectroscopy and images of the quadriceps were captured to calculate quadriceps volume. ATPmax (mM ATP/s) and oxidative capacity of the quadriceps (ATPmax·Quadriceps volume) were calculated. Peak aerobic capacity (VO2peak) was measured using a modified Balke protocol. RESULTS: ATPmax·Quadriceps volume was associated with VO2peak and was 162.61mM ATP·mL/s lower (p = .03) in those with high (rating of perceived exertion ≥10) versus low (rating of perceived exertion ≤9) fatigability. Participants with high fatigability required a significantly higher proportion of VO2peak to walk at 0.72 m/s compared with those with low fatigability (58.7 ± 19.4% vs 44.9 ± 13.2%, p < .05). After adjustment for age and sex, higher ATPmax was associated with lower odds of having high fatigability (odds ratio: 0.34, 95% CI: 0.11-1.01, p = .05). CONCLUSIONS: Lower capacity for oxidative phosphorylation in the quadriceps, perhaps by contributing to lower VO2peak, is associated with higher fatigability in older adults.
BACKGROUND: Fatigability increases while the capacity for mitochondrial energy production tends to decrease significantly with age. Thus, diminished mitochondrial function may contribute to higher levels of fatigability in older adults. METHODS: The relationship between fatigability and skeletal muscle mitochondrial function was examined in 30 participants aged 78.5 ± 5.0 years (47% female, 93% white), with a body mass index of 25.9 ± 2.7 kg/m(2) and usual gait-speed of 1.2 ± 0.2 m/s. Fatigability was defined using rating of perceived exertion (6-20 point Borg scale) after a 5-minute treadmill walk at 0.72 m/s. Phosphocreatine recovery in the quadriceps was measured using (31)P magnetic resonance spectroscopy and images of the quadriceps were captured to calculate quadriceps volume. ATPmax (mM ATP/s) and oxidative capacity of the quadriceps (ATPmax·Quadriceps volume) were calculated. Peak aerobic capacity (VO2peak) was measured using a modified Balke protocol. RESULTS:ATPmax·Quadriceps volume was associated with VO2peak and was 162.61mM ATP·mL/s lower (p = .03) in those with high (rating of perceived exertion ≥10) versus low (rating of perceived exertion ≤9) fatigability. Participants with high fatigability required a significantly higher proportion of VO2peak to walk at 0.72 m/s compared with those with low fatigability (58.7 ± 19.4% vs 44.9 ± 13.2%, p < .05). After adjustment for age and sex, higher ATPmax was associated with lower odds of having high fatigability (odds ratio: 0.34, 95% CI: 0.11-1.01, p = .05). CONCLUSIONS: Lower capacity for oxidative phosphorylation in the quadriceps, perhaps by contributing to lower VO2peak, is associated with higher fatigability in older adults.
Authors: Anna-Maria Joseph; Peter J Adhihetty; Thomas W Buford; Stephanie E Wohlgemuth; Hazel A Lees; Linda M-D Nguyen; Juan M Aranda; Bhanu D Sandesara; Marco Pahor; Todd M Manini; Emanuele Marzetti; Christiaan Leeuwenburgh Journal: Aging Cell Date: 2012-07-09 Impact factor: 9.304
Authors: Bryan Kestenbaum; Jorge Gamboa; Sophia Liu; Amir S Ali; Eric Shankland; Thomas Jue; Cecilia Giulivi; Lucas R Smith; Jonathan Himmelfarb; Ian H de Boer; Kevin Conley; Baback Roshanravan Journal: JCI Insight Date: 2020-03-12
Authors: Gwenael Layec; Joel D Trinity; Corey R Hart; Seong-Eun Kim; H Jonathan Groot; Yann Le Fur; Jacob R Sorensen; Eun-Kee Jeong; Russell S Richardson Journal: Am J Physiol Regul Integr Comp Physiol Date: 2015-06-03 Impact factor: 3.619
Authors: Andrea Braganza; Catherine G Corey; Adam J Santanasto; Giovanna Distefano; Paul M Coen; Nancy W Glynn; Seyed-Mehdi Nouraie; Bret H Goodpaster; Anne B Newman; Sruti Shiva Journal: JCI Insight Date: 2019-05-23
Authors: Patrick J Brown; Nicholas Brennan; Adam Ciarleglio; Chen Chen; Carolina Montes Garcia; Stephanie Gomez; Steven P Roose; Bret R Rutherford; Eleanor M Simonsick; Richard G Spencer; Luigi Ferrucci Journal: Am J Geriatr Psychiatry Date: 2019-04-06 Impact factor: 4.105
Authors: Adam R Konopka; Jaime L Laurin; Robert V Musci; Christopher A Wolff; Justin J Reid; Laurie M Biela; Qian Zhang; Fredrick F Peelor; Christopher L Melby; Karyn L Hamilton; Benjamin F Miller Journal: Geroscience Date: 2017-03-10 Impact factor: 7.713
Authors: Patrick J Brown; Bret R Rutherford; Kristine Yaffe; Jane M Tandler; Justina Laurence Ray; Emily Pott; Sarah Chung; Steven P Roose Journal: Am J Geriatr Psychiatry Date: 2016-06-23 Impact factor: 4.105