Skeletal Muscle Mitochondrial Function and 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.

[1]  D. Wallace,et al.  A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator , 1997, Nature Genetics.

[2]  H. Chung,et al.  Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle , 2008, Mechanisms of Ageing and Development.

[3]  L. Ferrucci,et al.  Assessing Fatigability in Mobility‐Intact Older Adults , 2014, Journal of the American Geriatrics Society.

[4]  W. Evans,et al.  Energetics of walking in elderly people: factors related to gait speed. , 2010, The journals of gerontology. Series A, Biological sciences and medical sciences.

[5]  Fennigje M. Purves-Smith,et al.  Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans , 2014, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[6]  R. Meyer,et al.  Linear dependence of muscle phosphocreatine kinetics on oxidative capacity. , 1997, The American journal of physiology.

[7]  R S Balaban,et al.  Nmr spectral analysis of kinetic data using natural lineshapes , 1990, Magnetic resonance in medicine.

[8]  G. Borg Borg's Perceived Exertion and Pain Scales , 1998 .

[9]  Marianne Schroll,et al.  Functional Decline From Age 80 to 85: Influence of Preceding Changes in Tiredness in Daily Activities , 2003, Psychosomatic medicine.

[10]  M. Tarnopolsky,et al.  Mitochondrial myopathies: diagnosis, exercise intolerance, and treatment options. , 2005, Medicine and science in sports and exercise.

[11]  L. Ferrucci,et al.  Skeletal muscle mitochondrial energetics are associated with maximal aerobic capacity and walking speed in older adults. , 2013, The journals of gerontology. Series A, Biological sciences and medical sciences.

[12]  P. Esselman,et al.  Oxidative capacity and ageing in human muscle , 2000, The Journal of physiology.

[13]  L. Ferrucci,et al.  Fatigue in a representative population of older persons and its association with functional impairment, functional limitation, and disability. , 2009, The journals of gerontology. Series A, Biological sciences and medical sciences.

[14]  D L Patrick,et al.  Screening for depression in well older adults: evaluation of a short form of the CES-D (Center for Epidemiologic Studies Depression Scale). , 1994, American journal of preventive medicine.

[15]  Melissa M. Thomas,et al.  Mitochondrial Structure and Function Are Disrupted by Standard Isolation Methods , 2011, PloS one.

[16]  J. Leigh,et al.  Relationships between in vivo and in vitro measurements of metabolism in young and old human calf muscles. , 1993, Journal of applied physiology.

[17]  R. Richardson,et al.  Human muscle performance and PCr hydrolysis with varied inspired oxygen fractions: a 31P-MRS study. , 1999, Journal of applied physiology.

[18]  I. Hickie,et al.  The characteristics of fatigue in an older primary care sample. , 2007, Journal of psychosomatic research.

[19]  K. Conley,et al.  Mitochondrial dysfunction and age , 2007, Current opinion in clinical nutrition and metabolic care.

[20]  L. Ferrucci,et al.  The Energetic Pathway to Mobility Loss: An Emerging New Framework for Longitudinal Studies on Aging , 2010, Journal of the American Geriatrics Society.

[21]  M. E. Cress,et al.  Ageing, muscle properties and maximal O2 uptake rate in humans , 2000, The Journal of physiology.

[22]  P. Esselman,et al.  Decline in isokinetic force with age: muscle cross-sectional area and specific force , 1997, Pflügers Archiv.

[23]  S. Studenski,et al.  Bedside‐to‐Bench Conference: Research Agenda for Idiopathic Fatigue and Aging , 2010, Journal of the American Geriatrics Society.

[24]  Stephen A. Foulis,et al.  Age-related changes in oxidative capacity differ between locomotory muscles and are associated with physical activity behavior. , 2012, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[25]  T. Manini,et al.  The impact of aging on mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high‐ and low‐functioning elderly individuals , 2012, Aging cell.

[26]  Christopher H. Morrell,et al.  Accelerated Longitudinal Decline of Aerobic Capacity in Healthy Older Adults , 2005, Circulation.

[27]  S. Dimauro Exercise intolerance and the mitochondrial respiratory chain , 1999, The Italian Journal of Neurological Sciences.

[28]  B. Eldadah Fatigue and Fatigability in Older Adults , 2010, PM & R : the journal of injury, function, and rehabilitation.

[29]  L. Ferrucci,et al.  A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. , 1994, Journal of gerontology.

[30]  C. Jessie Jones,et al.  The Reliability and Validity of a 6-Minute Walk Test as a Measure of Physical Endurance in Older Adults , 1998 .

[31]  J. Kent‐Braun,et al.  Is Skeletal Muscle Oxidative Capacity Decreased in Old Age? , 2004, Sports medicine.

[32]  D. Allen,et al.  The effects of intracellular injections of phosphate on intracellular calcium and force in single fibres of mouse skeletal muscle , 1996, Pflügers Archiv.

[33]  Melissa M. Thomas,et al.  Alterations in intrinsic mitochondrial function with aging are fiber type‐specific and do not explain differential atrophy between muscles , 2011, Aging cell.

[34]  R. Hepple,et al.  The role of O2 supply in muscle fatigue. , 2002, Canadian journal of applied physiology = Revue canadienne de physiologie appliquee.

[35]  P. Esselman,et al.  Individual variation in contractile cost and recovery in a human skeletal muscle. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[36]  James W Hardin,et al.  Cardiorespiratory fitness and adiposity as mortality predictors in older adults. , 2007, JAMA.

[37]  M. Tarnopolsky,et al.  Aberrant Mitochondrial Homeostasis in the Skeletal Muscle of Sedentary Older Adults , 2010, PloS one.

[38]  Susan E. Hardy,et al.  Qualities of fatigue and associated chronic conditions among older adults. , 2010, Journal of pain and symptom management.