Muscle strength mediates the relationship between mitochondrial energetics and walking performance

Ariel C Zane, David A Reiter, Michelle Shardell, Donnie Cameron, Eleanor M Simonsick, Kenneth W Fishbein, Stephanie A Studenski, Richard G Spencer, Luigi Ferrucci, Ariel C Zane, David A Reiter, Michelle Shardell, Donnie Cameron, Eleanor M Simonsick, Kenneth W Fishbein, Stephanie A Studenski, Richard G Spencer, Luigi Ferrucci

Abstract

Skeletal muscle mitochondrial oxidative capacity declines with age and negatively affects walking performance, but the mechanism for this association is not fully clear. We tested the hypothesis that impaired oxidative capacity affects muscle performance and, through this mechanism, has a negative effect on walking speed. Muscle mitochondrial oxidative capacity was measured by in vivo phosphorus magnetic resonance spectroscopy as the postexercise phosphocreatine resynthesis rate, kPCr , in 326 participants (154 men), aged 24-97 years (mean 71), in the Baltimore Longitudinal Study of Aging. Muscle strength and quality were determined by knee extension isokinetic strength, and the ratio of knee extension strength to thigh muscle cross-sectional area derived from computed topography, respectively. Four walking tasks were evaluated: a usual pace over 6 m and for 150 s, and a rapid pace over 6 m and 400 m. In multivariate linear regression analyses, kPCr was associated with muscle strength (β = 0.140, P = 0.007) and muscle quality (β = 0.127, P = 0.022), independent of age, sex, height, and weight; muscle strength was also a significant independent correlate of walking speed (P < 0.02 for all tasks) and in a formal mediation analysis significantly attenuated the association between kPCr and three of four walking tasks (18-29% reduction in β for kPCr ). This is the first demonstration in human adults that mitochondrial function affects muscle strength and that inefficiency in muscle bioenergetics partially accounts for differences in mobility through this mechanism.

Keywords: in vivo; 31P MRS; bioenergetics; muscle strength; skeletal muscle; walking speed.

© 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Age versus muscle strength stratified by age‐specific muscle strength tertiles, for 326 participants in the Baltimore Longitudinal Study of Aging.
Figure 2
Figure 2
Diagram illustrating: a) the demonstrated effect of kPC r on walking speeds (Choi et al., 2016), b) the effect of kPC r on muscle function, and c) the effect of kPC r on walking speeds, mediated by muscle function.

References

    1. Arnold D, Matthews P, Radda G (1984) Metabolic recovery after exercise and the assessment of mitochondrial function in vivo in human skeletal muscle by means of 31P NMR. Magn. Reson. Med. 1, 307–315.
    1. Bourdel‐Marchasson I, Biran M, Dehail P, Traissac T, Muller F, Jenn J, Raffard G, Franconi J, Thiaudiere E (2007) Muscle phosphocreatine post‐exercise recovery rate is related to functional evaluation in hospitalized and community‐living older people. J. Nutr. Health Aging 11, 215–221.
    1. Brierley EJ, Johnson MA, James OFW, Turnbull DM (1996) Effects of physical activity and age on mitochondrial function. QJM 89, 251–258.
    1. Cesari M, Kritchevsky SB, Newman AB, Simonsick EM, Harris TB, Penninx BW, Brach JS, Tylavsky FA, Satterfield S, Bauer DC, Rubin SM, Visser M, Pahor M (2009) Added value of physical performance measures in predicting adverse health‐related events: results from the health, aging, and body composition study. J. Am. Geriatr. Soc. 57, 251–259.
    1. Chance B, Eleff S, Leigh JS, Sokolow D, Sapega A (1981) Mitochondrial regulation of phosphocreatine/inorganic phosphate ratios in exercising human muscle: a gated 31P NMR study. Proc. Natl Acad. Sci. USA 78, 6714–6718.
    1. Choi S, Reiter DA, Shardell M, Simonsick EM, Studenski S, Spencer RG, Fishbein KW, Ferrucci L (2016) 31P magnetic resonance spectroscopy assessment of muscle bioenergetics as a predictor of gait speed in the baltimore longitudinal study of aging. J. Gerontol. A Biol. Sci. Med. Sci. 71, 1638–1645.
    1. Coen PM, Jubrias SA, Distefano G, Amati F, Mackey DC, Glynn NW, Manini TM, Wohlgemuth SE, Leeuwenburgh C, Cummings SR, Newman AB, Ferrucci L, Toledo FGS, Shankland E, Conley KE, Goodpaster BH (2013) Skeletal muscle mitochondrial energetics are associated with maximal aerobic capacity and walking speed in older adults. J. Gerontol. A Biol. Sci. Med. Sci. 68, 447–455.
    1. Conley KE, Jubrias SA, Esselman PC (2000) Oxidative capacity and ageing in human muscle. J. Physiol. 526, 203–210.
    1. Cunningham DA, Rechnitzer PA, Pearce ME, Donner AP (1982) Determinants of self‐selected walking pace across ages 19 to 66. J. Gerontol. 37, 560–564.
    1. Edwards LM, Tyler D, Kemp GJ, Dwyer RM, Johnson A, Holloway CJ, Nevill AM, Clarke K (2012) The reproducibility of 31‐phosphorus MRS measures of muscle energetics at 3 tesla in trained men. PLoS ONE 7, e37237.
    1. Ferrucci L, Cooper R, Shardell M, Simonsick EM, Schrack JA, Kuh D (2016) Age‐related change in mobility: perspectives from life course epidemiology and geroscience. J. Gerontol. A Biol. Sci. Med. Sci. 71, 1184–1194.
    1. Fleischman A, Makimura H, Stanley TL, McCarthy MA, Kron M, Sun N, Chuzi S, Hrovat MI, Systrom DM, Grinspoon SK (2010) Skeletal muscle phosphocreatine recovery after submaximal exercise in children and young and middle‐aged adults. J. Clin. Endocrinol. Metab. 95, E69–E74.
    1. Goodpaster BH, Park SW, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, Simonsick EM, Tylavsky FA, Visser M, Newman AB (2006) The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J. Gerontol. A Biol. Sci. Med. Sci. 61, 1059–1064.
    1. Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB (1995) Lower‐extremity function in persons over the age of 70 years as a predictor of subsequent disability. N. Engl. J. Med. 332, 556–561.
    1. Halter J, Ouslander J, Tinetti M, Studenski S, High K, Asthana S (2009) Hazzard's Geriatric Medicine and Gerontology. New York: McGraw‐Hill Education.
    1. Hartmann A, Knols R, Murer K, de Bruin ED (2009) Reproducibility of an isokinetic strength‐testing protocol of the knee and ankle in older adults. Gerontology 55, 259–268.
    1. Holmes KC, Geeves MA (2000) The structural basis of muscle contraction. Philos. Trans. R. Soc. Lond B Biol. Sci. 355, 419–431.
    1. Jubrias SA, Esselman PC, Price LB, Cress ME, Conley KE (2001) Large energetic adaptations of elderly muscle to resistance and endurance training. J. Appl. Physiol. 90, 1663–1670.
    1. Latham NK, Bennett DA, Stretton CM, Anderson CS (2004) Systematic review of progressive resistance strength training in older adults. J. Gerontol. A Biol. Sci. Med. Sci. 59, M48–M61.
    1. Manini TM, Clark BC (2012) Dynapenia and aging: an update. J. Gerontol. A Biol. Sci. Med. Sci. 67A, 28–40.
    1. McCully KK, Fielding RA, Evans WJ, Leigh JS, Posner JD (1993) Relationships between in vivo and in vitro measurements of metabolism in young and old human calf muscles. J. Appl. Physiol. 75, 813–819.
    1. McCully KK, Turner TN, Langley J, Zhao Q (2009) The reproducibility of measurements of intramuscular magnesium concentrations and muscle oxidative capacity using P MRS. Dyn. Med. 8, 5.
    1. McDermott MM, Criqui MH, Greenland P, Guralnik JM, Liu K, Pearce WH, Taylor L, Chan C, Celic L, Woolley C, O'Brien MP, Schneider JR (2004) Leg strength in peripheral arterial disease: associations with disease severity and lower‐extremity performance. J. Vasc. Surg. 39, 523–530.
    1. Metter EJ, Lynch N, Conwit R, Lindle R, Tobin J, Hurley B (1999) Muscle quality and age: cross‐sectional and longitudinal comparisons. J. Gerontol. A Biol. Sci. Med. Sci. 54, B207–B218.
    1. Meyer R (1988) A linear model of muscle respiration explains mono‐exponential phosphocreatine changes. Am. J. Physiol. Cell Physiol. 254, C548–C553.
    1. Moore AZ, Biggs ML, Matteini A, O'Connor A, McGuire S, Beamer BA, Fallin MD, Fried LP, Walston J, Chakravarti A, Arking DE (2010) Polymorphisms in the mitochondrial DNA control region and frailty in older adults. PLoS ONE 5, e11069.
    1. Moore AZ, Caturegli G, Metter EJ, Makrogiannis S, Resnick SM, Harris TB, Ferrucci L (2014) Difference in muscle quality over the adult life span and biological correlates in the baltimore longitudinal study of aging. J. Am. Geriatr. Soc. 62, 230–236.
    1. Naressi A, Couturier C, Castang I, de Beer R, Graveron‐Deilly D (2001) Java‐based graphical user interface for MRUI, a software package of quantitation of in vivo/medical magnetic resonance spectroscopy signals. Comput. Biol. Med. 31, 269–286.
    1. Newman AB, Kupelian V, Visser M, Simonsick EM, Goodpaster BH, Kritchevsky SB, Tylavsky FA, Rubin SM, Harris TB (2006) Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J. Gerontol. A Biol. Sci. Med. Sci. 61, 72–77.
    1. Peterson CM, Johannsen DL, Ravussin E (2012) Skeletal muscle mitochondria and aging: a review. J. Aging Res. 2012, 194821.
    1. Powers SK, Ji LL, Kavazis AN, Jackson MJ (2011) Reactive oxygen species: impact on skeletal muscle. Compr. Physiol. 1, 941–969.
    1. Santanasto AJ, Glynn NW, Jubrias SA, Conley KE, Boudreau RM, Amati F, Mackey DC, Simonsick EM, Strotmeyer ES, Coen PM, Goodpaster BH, Newman AB (2014) Skeletal muscle mitochondrial function and fatigability in older adults. J. Gerontol. A Biol. Sci. Med. Sci. 70, 1379–1385.
    1. Schrack JA, Simonsick EM, Chaves PHM, Ferrucci L (2012) The role of energetic cost in the age‐related slowing of gait speed. J. Am. Geriatr. Soc. 60, 1811–1816.
    1. Schrack JA, Simonsick EM, Ferrucci L (2013) The relationship of the energetic cost of slow walking and peak energy expenditure to gait speed in mid‐to‐late life. Am. J. Phys. Med. Rehabil. 92, 28–35.
    1. Shock NW, Greulich RC, Andres R, Arenberg D, Costa PT Jr, Lakatta EG, Tobin JD (1984) Normal Human Aging: The Baltimore Longitudinal Study of Aging. Washington, D.C.: NIH; Publication 84‐2450.
    1. Short KR, Bigelow ML, Kahl J, Singh R, Coenen‐Schimke J, Raghavakaimal S, Nair KS (2005) Decline in skeletal muscle mitochondrial function with aging in humans. Proc. Natl Acad. Sci. USA 102, 5618–5623.
    1. Simonsick EM, Montgomery PS, Newman AB, Bauer DC, Harris T (2001) Measuring fitness in healthy older adults: the health ABC long distance corridor walk. J. Am. Geriatr. Soc. 49, 1544–1548.
    1. Sivitz WI, Yorek MA (2010) Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxid. Redox. Sign. 12, 537–577.
    1. Smith SA, Montain SJ, Zientara GP, Fielding RA (2004) Use of phosphocreatine kinetics to determine the influence of creatine on muscle mitochondrial respiration: an in vivo 31P‐MRS study of oral creatine ingestion. J. Appl. Physiol. 96, 2288–2292.
    1. Stefan D, Cesare FD, Andrasescu A, Popa E, Lazariev A, Vescovo E, Strbak O, Williams S, Starcuk Z, Cabanas M, van Ormondt D, Graveron‐Demilly D (2009) Quantitation of magnetic resonance spectroscopy signals: the jMRUI software package. Measurement Science and Technology 20(10), 104035.
    1. Studenski S, Perera S, Patel K, et al (2011) Gait speed and survival in older adults. JAMA 305, 50–58.
    1. Vanhamme L, Van Huffel S, Van Hecke P, van Ormondt D (1999) Time‐domain quantification of series of biomedical magnetic resonance spectroscopy signals. J. Magn. Reson. 140, 120–130.
    1. Vestergaard S, Nayfield SG, Patel KV, Eldadah B, Cesari M, Ferrucci L, Ceresini G, Guralnik JM (2009) Fatigue in a representative population of older persons and its association with functional impairment, functional limitation, and disability. J. Gerontol. A Biol. Sci. Med. Sci. 64A, 76–82.
    1. Walsh B, Tonkonogi M, Söderlund K, Hultman E, Saks V, Sahlin K (2001) The role of phosphorylcreatine and creatine in the regulation of mitochondrial respiration in human skeletal muscle. J. Physiol. 537, 971–978.

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