标题：Genetic variants in the PPARD-PPARGC1A-NRF-TFAM mitochondriogenesis pathway are neither associated with muscle characteristics nor physical performance in elderly. [Variaciones genéticas en la vía de la mitocondriogénesis PPARD-PPARGC1A-NRF-TFAM no están asociadas ni con características musculares ni con rendimiento físico en personas mayores].
期刊名称：RICYDE. Revista Internacional de Ciencias del Deporte. doi:10.5232/ricyde
印刷版ISSN：1885-3137
出版年度：2015
卷号：11
期号：41
页码：196-208
语种：English
出版社：Ramón Cantó Alcaraz (Publisher)
摘要：We studied the influence of genetic polymorphisms involved in the PPARD-PPARGC1A-NRF-TFAM mitochondriogenesis pathway (rs6949152, rs12594956, rs2267668 , rs8192678 , and rs1937) on muscle phenotypes (thigh muscles’ cross-sectional, maximal handgrip-strength and 30-second chair stand-test) and Barthel index in Caucasian (Spanish) community-dwelling old people (n=75, 21 men, 54 women; 71–94 years). We found no significant genetic associations with the studied phenotypes. Multiple, complex gene-environment and gene-gene interactions which are yet to be determined are likely to play a more determinant role. Resumen Se estudió la influencia de los polimorfismos genéticos implicados en la vía de mitocondriogénesis PPARD-PPARGC1A-NRF-TFAM (rs6949152, rs12594956, rs2267668, rs8192678 y rs1937) en distintos fenotipos musculares (sección transversal muscular del muslo, fuerza máxima de prensión manual y 30 segundos de sentarse-levantarse de una silla) y en el índice de Barthel en personas mayores caucásicas (españoles) (n = 75, 21 hombres, 54 mujeres; 71 a 94 años). No se encontraron asociaciones genéticas significativas con los fenotipos estudiados. Interacciones múltiples, complejos gen-ambiente y relaciones gen-gen aún no determinadas podrían desempeñar un papel más determinante. http://dx.doi.org/10.5232/ricyde2015.04101 -------------------------------------------------------------------------- References/referencias Attia, J.; Ioannidis, J. P.; Thakkinstian, A.; McEvoy, M.; Scott, R. J.; Minelli, C.; . . . Guyatt, G. (2009). How to use an article about genetic association: B: Are the results of the study valid? JAMA-Journal of the American Medical Association, 301 (2), 191-197. http://dx.doi.org/10.1001/jama.2008.946 Baztán, J. J.; Pérez del Molino, J.; Alarcón, T.; San Cristóbal, E.; Izquierdo, G., & Manzarbeitia, J. (1993). Índice de Barthel: Instrumento válido para la valoración funcional de pacientes con enfermedad cerebrovascular. Revista Española de Geriatría y Gerontología, 128 , 32-40. Berger, J., & Moller, D. E. (2002). The mechanisms of action of PPARs. Annual review of medicine, 53 , 409-435. http://dx.doi.org/10.1146/annurev.med.53.082901.104018 Chanock, S.J.; Manolio, T.; Boehnke, M.; Boerwinkle, E.; Hunter, D.J.;, Thomas, G.; . . . Collins, F.S. (2007) Replicating genotype-phenotype associations. Nature (2007). 447(7145):655–660. http://dx.doi.org/10.1038/447655a Collin, C.; Wade, D. T.; Davies, S., & Horne, V. (1988). The Barthel ADL Index: a reliability study. International Disabilility Studies, 10 (2), 61-63. De Abajo, S.; Larriba, R., & Marquez, S. (2001). Validity and reliability of the Yale Physical Activity Survey in Spanish elderly. Journal of Sports Medicine and Physical Fitness, 41 (4), 479-485. Dipietro, L.; Caspersen, C. J.; Ostfeld, A. M., & Nadel, E. R. (1993). A survey for assessing physical activity among older adults. Medicine & Science in Sports & Exercise, 25 (5), 628-642. Fannin, S. W.; Lesnefsky, E. J.; Slabe, T. J.; Hassan, M. O., & Hoppel, C. L. (1999). Aging selectively decreases oxidative capacity in rat heart interfibrillar mitochondria. Archives of biochemistry and biophysics, 372 (2), 399-407. http://dx.doi.org/10.1006/abbi.1999.1508 Fitzmaurice, G. (2002). Statistical methods for assessing agreement. Nutrition, 18 (7-8), 694-696. Flueck, M.; Eyeang-Bekale, N.; Heraud, A.; Girard, A.; Gimpl, M.; Seynnes, O. R.; . . . Narici, M. (2011). Load-sensitive adhesion factor expression in the elderly with skiing: relation to fiber type and muscle strength. Scandinavian Journal of Medicine & Science in Sports, 21 Suppl 1 , 29-38. http://dx.doi.org/10.1111/j.1600-0838.2011.01339.x Garatachea, N.; Fiuza-Luces, C.; Torres-Luque, G.; Yvert, T.; Santiago, C.; Gomez-Gallego, F.; . . . Lucia, A. (2011). Single and combined influence of ACE and ACTN3 genotypes on muscle phenotypes in octogenarians. European Journal of Applied Physiology . http://dx.doi.org/10.1007/s00421-011-2217-4 Garesse, R., & Vallejo, C. G. (2001). Animal mitochondrial biogenesis and function: a regulatory cross-talk between two genomes. Gene, 263 (1-2), 1-16. Gotshalk, L. A.; Volek, J. S.; Staron, R. S.; Denegar, C. R.; Hagerman, F. C., & Kraemer, W. J. (2002). Creatine supplementation improves muscular performance in older men. Medicine & Science in Sports & Exercise, 34 (3), 537-543. Harriss, D. J., & Atkinson, G. (2011). Update--Ethical standards in sport and exercise science research. International journal of sports medicine, 32 (11), 819-821. http://dx.doi.org/10.1055/s-0031-1287829 Hood, D. A. (2009). Mechanisms of exercise-induced mitochondrial biogenesis in skeletal muscle. Applied Physiology, Nutrition, and Metabolism, 34 (3), 465-472. Jones, C. J.; Rikli, R. E., & Beam, W. C. (1999). A 30-s chair-stand test as a measure of lower body strength in community-residing older adults. Research Quarterly for Exercise & Sport, 70 (2), 113-119. Kanki, T.; Ohgaki, K.; Gaspari, M.; Gustafsson, C. M.; Fukuoh, A.; Sasaki, N.; . . . Kang, D. (2004). Architectural role of mitochondrial transcription factor A in maintenance of human mitochondrial DNA. Molecular and cellular biology, 24 (22), 9823-9834. http://dx.doi.org/10.1128/MCB.24.22.9823-9834.2004 Larsson, N. G.; Wang, J.; Wilhelmsson, H.; Oldfors, A.; Rustin, P.; Lewandoski, M.; . . . Clayton, D. A. (1998). Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nature genetics, 18 (3), 231-236. http://dx.doi.org/10.1038/ng0398-231 Lopez-Lluch, G.; Irusta, P. M.; Navas, P., & de Cabo, R. (2008). Mitochondrial biogenesis and healthy aging. Experimental gerontology, 43 (9), 813-819. http://dx.doi.org/10.1016/j.exger.2008.06.014 Mahoney, F. I., & Barthel, D. W. (1965). Functional Evaluation: The Barthel Index. Maryland State Medical Journal, 14 , 61-65. Nair, K. S. (2005). Aging muscle. The American journal of clinical nutrition, 81 (5), 953-963. Rikli, R. E., & Jones, C. J. (1999). Development and validation of a funcional fitness test for comunityresiding older adults. Journal of Aging Physical Activity, 7 (2), 129-161. Ruiz-Ruiz J, Mesa JL, Gutierrez A, Castillo MJ (2002) Hand sizeinfluences optimal grip span in women but not in men. Journal of Hand Surgery, 27(5):897–901. Puigserver, P.; Adelmant, G.; Wu, Z.; Fan, M.; Xu, J.; O´Malley, B. & Spiegelman, B.M. (1999) Activacion of PPARgamma coactivator-1 through transcription factor docking. Science , 286(5443):1368-1371. Puigserver, P. & Spiegelman, B.M. (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocrine Reviews , 24(1):78-90. Shah, V. O.; Scariano, J.; Waters, D.; Qualls, C.; Morgan, M.; Pickett, G.; . . . Raj, D. S. (2009). Mitochondrial DNA deletion and sarcopenia. Genetics in medicine : official journal of the American College of Medical Genetics, 11 (3), 147-152. http://dx.doi.org/10.1097/GIM.0b013e31819307a2 Short, K. R.; Bigelow, M. L.; Kahl, J.; Singh, R.; Coenen-Schimke, J.; Raghavakaimal, S., & Nair, K. S. (2005). Decline in skeletal muscle mitochondrial function with aging in humans. Proceedings of the National Academy of Sciences of the United States of America, 102 (15), 5618-5623. http://dx.doi.org/10.1073/pnas.0501559102 Stefan, N.; Thamer, C.; Staiger, H.; Machicao, F.; Machann, J.; Schick, F.; . . . Haring, H. U. (2007). Genetic variations in PPARD and PPARGC1A determine mitochondrial function and change in aerobic physical fitness and insulin sensitivity during lifestyle intervention. The Journal of clinical endocrinology and metabolism, 92 (5), 1827-1833. http://dx.doi.org/10.1210/jc.2006-1785 Sugiyama, S.; Takasawa, M.; Hayakawa, M., & Ozawa, T. (1993). Changes in skeletal muscle, heart and liver mitochondrial electron transport activities in rats and dogs of various ages. Biochemistry and molecular biology international, 30 (5), 937-944. Thamer, C.; Machann, J.; Stefan, N.; Schafer, S. A.; Machicao, F.; Staiger, H.; . . . Haring, H. U. (2008). Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study. The Journal of clinical endocrinology and metabolism, 93 (4), 1497-1500. http://dx.doi.org/10.1210/jc.2007-1209 Vieira, S., & Corrente, J. E. (2011). Statistical methods for assessing agreement between double readings of clinical measurements. Journal of applied oral science : revista FOB, 19 (5), 488-492. Vina, J.; Gomez-Cabrera, M. C.; Borras, C.; Froio, T.; Sanchis-Gomar, F.; Martinez-Bello, V. E., & Pallardo, F. V. (2009a). Mitochondrial biogenesis in exercise and in ageing. Advanced Drug Delivery Reviews, 61 (14), 1369-1374. Vina, J.; Gomez-Cabrera, M. C.; Borras, C., Froio, T.; Sanchis-Gomar, F.; Martinez-Bello, V. E., & Pallardo, F. V. (2009b). Mitochondrial biogenesis in exercise and in ageing. Advanced drug delivery reviews, 61 (14), 1369-1374. http://dx.doi.org/10.1016/j.addr.2009.06.006 Wisloff, U.; Najjar, S. M.; Ellingsen, O.; Haram, P. M.; Swoap, S.; Al-Share, Q.; . . . Britton, S. L. (2005). Cardiovascular risk factors emerge after artificial selection for low aerobic capacity. Science, 307 (5708), 418-420. Wu, Z.; Puigserver, P.; Andersson, U.; Zhang, C.; Adelmant, G.; Mootha, V.; . . . Spiegelman, B.M. (1999). Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell, 98(1): 115-124.
其他摘要：We studied the influence of genetic polymorphisms involved in the PPARD-PPARGC1A-NRF-TFAM mitochondriogenesis pathway (rs6949152, rs12594956, rs2267668 , rs8192678 , and rs1937) on muscle phenotypes (thigh muscles’ cross-sectional, maximal handgrip-strength and 30-second chair stand-test) and Barthel index in Caucasian (Spanish) community-dwelling old people (n=75, 21 men, 54 women; 71–94 years). We found no significant genetic associations with the studied phenotypes. Multiple, complex gene-environment and gene-gene interactions which are yet to be determined are likely to play a more determinant role. Resumen Se estudió la influencia de los polimorfismos genéticos implicados en la vía de mitocondriogénesis PPARD-PPARGC1A-NRF-TFAM (rs6949152, rs12594956, rs2267668, rs8192678 y rs1937) en distintos fenotipos musculares (sección transversal muscular del muslo, fuerza máxima de prensión manual y 30 segundos de sentarse-levantarse de una silla) y en el índice de Barthel en personas mayores caucásicas (españoles) (n = 75, 21 hombres, 54 mujeres; 71 a 94 años). No se encontraron asociaciones genéticas significativas con los fenotipos estudiados. Interacciones múltiples, complejos gen-ambiente y relaciones gen-gen aún no determinadas podrían desempeñar un papel más determinante. http://dx.doi.org/10.5232/ricyde2015.04101 -------------------------------------------------------------------------- References/referencias Attia, J.; Ioannidis, J. P.; Thakkinstian, A.; McEvoy, M.; Scott, R. J.; Minelli, C.; . . . Guyatt, G. (2009). How to use an article about genetic association: B: Are the results of the study valid? JAMA-Journal of the American Medical Association, 301 (2), 191-197. http://dx.doi.org/10.1001/jama.2008.946 Baztán, J. J.; Pérez del Molino, J.; Alarcón, T.; San Cristóbal, E.; Izquierdo, G., & Manzarbeitia, J. (1993). Índice de Barthel: Instrumento válido para la valoración funcional de pacientes con enfermedad cerebrovascular. Revista Española de Geriatría y Gerontología, 128 , 32-40. Berger, J., & Moller, D. E. (2002). The mechanisms of action of PPARs. Annual review of medicine, 53 , 409-435. http://dx.doi.org/10.1146/annurev.med.53.082901.104018 Chanock, S.J.; Manolio, T.; Boehnke, M.; Boerwinkle, E.; Hunter, D.J.;, Thomas, G.; . . . Collins, F.S. (2007) Replicating genotype-phenotype associations. Nature (2007). 447(7145):655–660. http://dx.doi.org/10.1038/447655a Collin, C.; Wade, D. T.; Davies, S., & Horne, V. (1988). The Barthel ADL Index: a reliability study. International Disabilility Studies, 10 (2), 61-63. De Abajo, S.; Larriba, R., & Marquez, S. (2001). Validity and reliability of the Yale Physical Activity Survey in Spanish elderly. Journal of Sports Medicine and Physical Fitness, 41 (4), 479-485. Dipietro, L.; Caspersen, C. J.; Ostfeld, A. M., & Nadel, E. R. (1993). A survey for assessing physical activity among older adults. Medicine & Science in Sports & Exercise, 25 (5), 628-642. Fannin, S. W.; Lesnefsky, E. J.; Slabe, T. J.; Hassan, M. O., & Hoppel, C. L. (1999). Aging selectively decreases oxidative capacity in rat heart interfibrillar mitochondria. Archives of biochemistry and biophysics, 372 (2), 399-407. http://dx.doi.org/10.1006/abbi.1999.1508 Fitzmaurice, G. (2002). Statistical methods for assessing agreement. Nutrition, 18 (7-8), 694-696. Flueck, M.; Eyeang-Bekale, N.; Heraud, A.; Girard, A.; Gimpl, M.; Seynnes, O. R.; . . . Narici, M. (2011). Load-sensitive adhesion factor expression in the elderly with skiing: relation to fiber type and muscle strength. Scandinavian Journal of Medicine & Science in Sports, 21 Suppl 1 , 29-38. http://dx.doi.org/10.1111/j.1600-0838.2011.01339.x Garatachea, N.; Fiuza-Luces, C.; Torres-Luque, G.; Yvert, T.; Santiago, C.; Gomez-Gallego, F.; . . . Lucia, A. (2011). Single and combined influence of ACE and ACTN3 genotypes on muscle phenotypes in octogenarians. European Journal of Applied Physiology . http://dx.doi.org/10.1007/s00421-011-2217-4 Garesse, R., & Vallejo, C. G. (2001). Animal mitochondrial biogenesis and function: a regulatory cross-talk between two genomes. Gene, 263 (1-2), 1-16. Gotshalk, L. A.; Volek, J. S.; Staron, R. S.; Denegar, C. R.; Hagerman, F. C., & Kraemer, W. J. (2002). Creatine supplementation improves muscular performance in older men. Medicine & Science in Sports & Exercise, 34 (3), 537-543. Harriss, D. J., & Atkinson, G. (2011). Update--Ethical standards in sport and exercise science research. International journal of sports medicine, 32 (11), 819-821. http://dx.doi.org/10.1055/s-0031-1287829 Hood, D. A. (2009). Mechanisms of exercise-induced mitochondrial biogenesis in skeletal muscle. Applied Physiology, Nutrition, and Metabolism, 34 (3), 465-472. Jones, C. J.; Rikli, R. E., & Beam, W. C. (1999). A 30-s chair-stand test as a measure of lower body strength in community-residing older adults. Research Quarterly for Exercise & Sport, 70 (2), 113-119. Kanki, T.; Ohgaki, K.; Gaspari, M.; Gustafsson, C. M.; Fukuoh, A.; Sasaki, N.; . . . Kang, D. (2004). Architectural role of mitochondrial transcription factor A in maintenance of human mitochondrial DNA. Molecular and cellular biology, 24 (22), 9823-9834. http://dx.doi.org/10.1128/MCB.24.22.9823-9834.2004 Larsson, N. G.; Wang, J.; Wilhelmsson, H.; Oldfors, A.; Rustin, P.; Lewandoski, M.; . . . Clayton, D. A. (1998). Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nature genetics, 18 (3), 231-236. http://dx.doi.org/10.1038/ng0398-231 Lopez-Lluch, G.; Irusta, P. M.; Navas, P., & de Cabo, R. (2008). Mitochondrial biogenesis and healthy aging. Experimental gerontology, 43 (9), 813-819. http://dx.doi.org/10.1016/j.exger.2008.06.014 Mahoney, F. I., & Barthel, D. W. (1965). Functional Evaluation: The Barthel Index. Maryland State Medical Journal, 14 , 61-65. Nair, K. S. (2005). Aging muscle. The American journal of clinical nutrition, 81 (5), 953-963. Rikli, R. E., & Jones, C. J. (1999). Development and validation of a funcional fitness test for comunityresiding older adults. Journal of Aging Physical Activity, 7 (2), 129-161. Ruiz-Ruiz J, Mesa JL, Gutierrez A, Castillo MJ (2002) Hand sizeinfluences optimal grip span in women but not in men. Journal of Hand Surgery, 27(5):897–901. Puigserver, P.; Adelmant, G.; Wu, Z.; Fan, M.; Xu, J.; O´Malley, B. & Spiegelman, B.M. (1999) Activacion of PPARgamma coactivator-1 through transcription factor docking. Science , 286(5443):1368-1371. Puigserver, P. & Spiegelman, B.M. (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocrine Reviews , 24(1):78-90. Shah, V. O.; Scariano, J.; Waters, D.; Qualls, C.; Morgan, M.; Pickett, G.; . . . Raj, D. S. (2009). Mitochondrial DNA deletion and sarcopenia. Genetics in medicine : official journal of the American College of Medical Genetics, 11 (3), 147-152. http://dx.doi.org/10.1097/GIM.0b013e31819307a2 Short, K. R.; Bigelow, M. L.; Kahl, J.; Singh, R.; Coenen-Schimke, J.; Raghavakaimal, S., & Nair, K. S. (2005). Decline in skeletal muscle mitochondrial function with aging in humans. Proceedings of the National Academy of Sciences of the United States of America, 102 (15), 5618-5623. http://dx.doi.org/10.1073/pnas.0501559102 Stefan, N.; Thamer, C.; Staiger, H.; Machicao, F.; Machann, J.; Schick, F.; . . . Haring, H. U. (2007). Genetic variations in PPARD and PPARGC1A determine mitochondrial function and change in aerobic physical fitness and insulin sensitivity during lifestyle intervention. The Journal of clinical endocrinology and metabolism, 92 (5), 1827-1833. http://dx.doi.org/10.1210/jc.2006-1785 Sugiyama, S.; Takasawa, M.; Hayakawa, M., & Ozawa, T. (1993). Changes in skeletal muscle, heart and liver mitochondrial electron transport activities in rats and dogs of various ages. Biochemistry and molecular biology international, 30 (5), 937-944. Thamer, C.; Machann, J.; Stefan, N.; Schafer, S. A.; Machicao, F.; Staiger, H.; . . . Haring, H. U. (2008). Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study. The Journal of clinical endocrinology and metabolism, 93 (4), 1497-1500. http://dx.doi.org/10.1210/jc.2007-1209 Vieira, S., & Corrente, J. E. (2011). Statistical methods for assessing agreement between double readings of clinical measurements. Journal of applied oral science : revista FOB, 19 (5), 488-492. Vina, J.; Gomez-Cabrera, M. C.; Borras, C.; Froio, T.; Sanchis-Gomar, F.; Martinez-Bello, V. E., & Pallardo, F. V. (2009a). Mitochondrial biogenesis in exercise and in ageing. Advanced Drug Delivery Reviews, 61 (14), 1369-1374. Vina, J.; Gomez-Cabrera, M. C.; Borras, C., Froio, T.; Sanchis-Gomar, F.; Martinez-Bello, V. E., & Pallardo, F. V. (2009b). Mitochondrial biogenesis in exercise and in ageing. Advanced drug delivery reviews, 61 (14), 1369-1374. http://dx.doi.org/10.1016/j.addr.2009.06.006 Wisloff, U.; Najjar, S. M.; Ellingsen, O.; Haram, P. M.; Swoap, S.; Al-Share, Q.; . . . Britton, S. L. (2005). Cardiovascular risk factors emerge after artificial selection for low aerobic capacity. Science, 307 (5708), 418-420. Wu, Z.; Puigserver, P.; Andersson, U.; Zhang, C.; Adelmant, G.; Mootha, V.; . . . Spiegelman, B.M. (1999). Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell, 98(1): 115-124.
