The effects of aging on muscle loss and tissue-specific levels of NF-κB and SIRT6 proteins in rats
Affiliation(s)
Food Science and Nutrition Department, California Polytechnic State University, San Luis Obispo, USA. Department of Nutrition, Exercise and Health Sciences, Central Washington University, Ellensburg, USA.
Food Science and Nutrition Department, California Polytechnic State University, San Luis Obispo, USA. Department of Nutrition, Exercise and Health Sciences, Central Washington University, Ellensburg, USA.
ABSTRACT
The objective of this study was to examine the influence of aging on food intake, tissue and organ mass and NF-κB and SIRT6 levels in various tissues. The transcription factor, Nuclear Factor Kappa-B (NF-κB), is associated with both catabolic and anabolic pathways of muscle metabolism and may be involved in age-related muscle loss. SIRT6 is a member of the sirtuin family of proteins that function as protein lysine deacetylases and are associated with longevity in a number of organisms. Male Sprague-Dawley rats, aged 6 months (Adult) and 21 months (Old) were fed a commercially available diet for 10-17 days. Old rats consumed less food per body weight (BW) each day than Adult rats (1.45% g diet/g BW vs. 2.4% g diet/g BW). However, when intake data were expressed as g/diet per day there was no significant difference between groups. For skeletal muscle tissue, the average mass of gastrocnemius and soleus (g muscle/g BW) was significantly lower in Old rats. Levels of NF-κB (p65/RelA) and SIRT6 were measured by Western blot analysis in gastrocnemius, tibialis anterior, quadriceps, soleus, lung, heart, kidney and liver. NF-κB levels were higher in gastroc- nemius of Old rats compared to Adult rats. No significant age-specific differences in SIRT6 protein levels were noted in the tissues examined. Interestingly, when examined independent of age, levels of SIRT6 were significantly different between certain tissues. Data from this study suggest that aging affects muscle loss and NF-κB in a tissue-specific manner. Furthermore, these findings indicate tissue-specific but not age-specific differences in SIRT6 protein levels.
Cite this paper
LaGuire, T. , Kohlen, C. , Hawk, S. and Reaves, S. (2013) The effects of aging on muscle loss and tissue-specific levels of NF-κB and SIRT6 proteins in rats. Advances in Aging Research, 2, 1-9. doi: 10.4236/aar.2013.21001.
LaGuire, T. , Kohlen, C. , Hawk, S. and Reaves, S. (2013) The effects of aging on muscle loss and tissue-specific levels of NF-κB and SIRT6 proteins in rats. Advances in Aging Research, 2, 1-9. doi: 10.4236/aar.2013.21001.
References
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[1] Kumar, A., Takada, Y. and Boriek, A.M. (2004) Nuclear factor-κB: Its role in health and disease. Journal of Molecular Medicine, 82, 434-448. doi:10.1007/s00109-004-0555-y [2] Hayden, M.S. and Ghosh, S. (2004) Signaling to NF kappaB. Genes & Development, 18, 2195-2224. doi:10.1101/gad.1228704 [3] Jackman, R.E. and Kandarian, S.C. (2004) The molecular basis of skeletal muscle atrophy. American Journal of Physiology, 287, C834-C843. doi:10.1152/ajpcell.00579.2003 [4] Cai, D., Frantz, J.D., Tawa Jr., N.E., Melendez, P.A., Oh, B.-C., Lidov, H.G.W., Hasselgren, P.-O., Frontera, W.R., Lee, J., Gloss, D.J. and Shoelson, S.E. (2004) IKKbeta/ NF-kappaB activation causes severe muscle wasting in mice. Cell, 119, 285-298. doi:10.1016/j.cell.2004.09.027 [5] Mourkioti, F., Kratsios, P., Luedde, T., Song, Y.H., Delafontaine, P., Adami, R., Parente, V., Bottinelli, R., Pasparakis, M. and Rosenthal, N. (2006) Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration. Journal of Clinical Investigation, 116, 2945-2954. doi:10.1172/JCI28721 [6] Bar-Shai, M., Carmeli, E. and Reznick, A.Z. (2005) The role of NF-κB in protein breakdown in immobilization, aging, and exercise. New York Academy of Sciences, 1057, 431-447. [7] Salminen, A., Huuskonen, J., Ojala, J., Kauppinen, A., Kaarniranta, K. and Suuronen, T. (2008) Activation of innate immunity system during aging: NF-κB signaling is the molecular culprit of inflamm-aging. Ageing Research Reviews, 7, 83-105. doi:10.1016/j.arr.2007.09.002 [8] Taylor, D.M., Maxwell, M.M., Luthi-Carter, R. and Kazantsev, A.G. (2008) Biological and potential therapeutic roles of sirtuin deacetylases. Cellular and Molecular Life Sciences, 65, 4000-4018. doi:10.1007/s00018-008-8357-y [9] Yeung, F., Hoberg, J., Ramsey, C., Keller, M., Jones, D., Frye, R. and Mayo, M. (2004) Modulation of NF-kappaB dependent transcription and cell survival by the SIRT1 deacetylase. The EMBO Journal, 23, 2369-2380. doi:10.1038/sj.emboj.7600244 [10] Mostoslavsky, R., Chua, K.F., Lombard, D.B., Pang, W.W., Fischer, M.R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M.M., Mills, K.D., Patel, P., Hsu, J.T., Hong, A.L., Ford, E., Cheng, H.L., Kennedy, C., Nunez, N., Bronson, R., Frendewey, D., Auerbach, W., Valenzuela, D., Karow, M., Hottiger, M.O., Hursting, S., Barrett, J.C., Guarente, L., Mulligan, R., Demple, B., Yancopoulos, G.D. and Alt, F.W. (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell, 124, 315-329. doi:10.1016/j.cell.2005.11.044 [11] Lombard, D.B. (2009) Sirtuins at the breaking point: SIRT6 in DNA repair. Aging, 1, 12-16. [12] Michishita, E., McCord, R.A., Berber, E., Kioi, M., Pa dilla-Nash, H., Damian, M., Cheung, P., Kusumoto, R., Kawahara, T.L., Barrett, J.C., Chang, H.Y., Bohr, V.A., Ried, T., Gozani, O. and Chua, K.F. (2008) SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature, 452, 492-496. doi:10.1038/nature06736 [13] McCord, R.A., Michishita, E., Hong, T., Berber, E., Boxer, L.D., Kusumoto, R., Guan, S., Shi, X., Gozani, O., Burlingame, A.L., Bohr, V.A. and Chua, K.F. (2009) SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair. Aging (Albany NY), 1, 109-121. [14] Cameron, T.P., Lattuada, C.P., Kornreich, M.R. and Tarone, R.E. (1982) Longevity and reproductive comparisons for male ACI and Sprague-Dawley rat aging colonies. Laboratory Animal Science, 32, 495-499. [15] Li, Q. and Verma, I.M. (2002) NF-kappaB regulation in the immune system. Nature Reviews Immunology, 2, 725 734. doi:10.1038/nri910 [16] Schmitz, M.L. and Baeuerle, P.A. (1991) The p65 subunit is responsible for the strong transcription activating potential of NF-kappa. The EMBO Journal, 10, 3805-3817. [17] Kawahara, T.L.A., Michishita, E., Adler, A.S., Damian, M., Berber, E., Lin, M., McCord, R.A., Ongaigui, K.C.L., Boxer, L.D., Chang, H.Y. and Chua, K.F. (2009) SIRT6 links histone H3 lysine 9 deacetylation to NF-κB-dependent gene expression and organismal life span. Cell, 136, 62-74. doi:10.1016/j.cell.2008.10.052 [18] Delano, M.J. and Moldawer, L.L. (2006) The origins of cachexia in acute and chronic inflammatory diseases. Nutrition in Clinical Practice, 21, 68-81. doi:10.1177/011542650602100168 [19] Morley, J.E., Thomas, D.R. and Wilson, M.-M. (2006) Cachexia: Pathophysiology and clinical relevance. The American Journal of Clinical Nutrition, 83l, 735-743. [20] Greenlund, L.J. and Nair, K.S. (2003) Sarcopenia-conse quences, mechanisms, and potential therapies. Mechanisms of Ageing and Development, 124, 287-299. doi:10.1016/S0047-6374(02)00196-3 [21] Thomas, C.R. (2007) Loss of skeletal muscle mass in aging: Examining the relationship of starvation, sarcopenia and cachexia. Clinical Nutrition, 26, 389-399. doi:10.1016/j.clnu.2007.03.008 [22] Ventadour, S. and Attaix, D. (2006) Mechanisms of ske letal muscle atrophy. Current Opinion in Rheumatology, 18, 631-635. doi:10.1097/01.bor.0000245731.25383.de [23] Eley, H.L. and Tisdale, M.J. (2007) Skeletal muscle atrophy, a link between depression of protein synthesis and increase in degradation. The Journal of Biological Chemistry, 282, 7087-7097. doi:10.1074/jbc.M610378200 [24] Zaidi, G., Panda, H. and Supakar, P.C. (2005) Increased phosphorylation and decreased level of IkBx during aging in rat liver. Biogerontology, 6, 141-145. doi:10.1007/s10522-005-3459-5 [25] Kaufmann, J.A., Bickfore, P.C. and Taglialatela, G. (2002) Free radical-dependent changes in constitutive Nuclear factor kappa B in the aged hippocampus. Neuroreport, 13, 1917-1920. doi:10.1097/00001756-200210280-00017 [26] Korhonen, P., Helenius, M. and Salminen, A. (1997) Age related changes in the regulation of transcription factor NF-kappa G in rat brain. Neuroscience Letters, 225, 61 64. doi:10.1016/S0304-3940(97)00190-0 [27] Helenius, M., Hanninen, M., Lehtinen, S.K. and Salminen, A. (1996) Aging-induced up-regulation of nuclear binding activities of oxidative stress responsive NF-κB transcription factor in mouse cardiac muscle. Journal of Molecular and Cellular Cardiology, 28, 487-498. doi:10.1006/jmcc.1996.0045 [28] Helenius, M., Kyrylenko, S., Vehvilainen, P. and Salminen, A. (2001) Characterization of aging-associated up regulation of constitutive nuclear factor-kappa B binding activity. Antioxidants & Redox Signaling, 3, 147-156. doi:10.1089/152308601750100669 [29] Jia, G., Su, L., Singhai, S. and Liu, X. (2012) Emerging roles of SIRT6 on telomere maintenance, DNA repair, metabolism and mammalian aging. Molecular and Cellular Biochemistry, 364, 345-350. doi:10.1007/s11010-012-1236-8 [30] Kawahara, T.L.A., Rapicavoli, N.A., Wu, A.R., Qu, K., Quake, S.R. and Chang, H.Y. (2011) Dynamic chromatin localization of sirt6 shapes stress and aging-related transcriptional networks. PLOS Genetics, 7, Article ID: e1002153. doi:10.1371/journal.pgen.1002153