Physical exercise represents one of the most effective approaches to anti-aging. The goal of this study was to verify the effects of different modes and intensities of exercise on longevity proteins in the skeletal muscle in midlife. Middle-aged mice were trained in aerobic or resistance exercise for 8 weeks, and the changes in sirtuin 1 (SIRT1), adenosine monophosphate-activated kinase (AMPK), and mammalian target of rapamycin (mTOR) pathways in the skeletal muscle were evaluated by western blotting. Long-term exercise had no effects on skeletal muscle SIRT1 abundance, whereas high-intensity aerobic exercise increased AMPK phosphorylation and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Low-intensity resistance exercise facilitated Akt/mTOR/p70 ribosomal protein kinase S6 (p70S6K) signaling but did not induce muscle hypertrophy. Conversely, high-intensity resistance exercise stimulated muscle hypertrophy without phosphorylation of mTOR signaling-related proteins. These results suggest the importance of setting exercise modes and intensities for anti-aging in midlife.
Wyss-Coray T. Ageing, neurodegeneration and brain rejuvenation. Nature 2016; 539(7628): 180–186. https://doi.org/10.1038/nature20411.
Garatachea N, Pareja-Galeano H, Sanchis-Gomar F, Santos-Lozano A, Fiuza-Luces C, Morán M, et al. Exercise attenuates the major hallmarks of aging. Rejuvenation Res 2015; 18(1): 57–89. https://doi.org/10.1089/rej.2014.1623.
Patel KV, Coppin AK, Manini TM, Lauretani F, Bandinelli S, Ferrucci L, et al. Midlife physical activity and mobility in older age: the InCHIANTI study. Am J Prev Med 2006; 31(3): 217–224. https://doi.org/10.1016/j.amepre.2006.05.005.
Yu M, Zhang H, Wang B, Zhang Y, Zheng X, Shao B, et al. Key signaling pathways in aging and potential interventions for healthy aging. Cells 2021; 10(3): 660. https://doi.org/10.3390/cells10030660.
Ruderman NB, Xu XJ, Nelson L, Cacicedo JM, Saha AK, Lan F, et al. AMPK and SIRT1: a long-standing partnership? Am J Physiol Endocrinol Metab 2010; 298(4): E751–E760. https://doi.org/10.1152/ajpendo.00745.2009.
Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 2012; 149(2): 274–293. https://doi.org/10.1016/j.cell.2012.03.017.
Chen Z-P, Stephens TJ, Murthy S, Canny BJ, Hargreaves M, Witters LA, et al. Effect of exercise intensity on skeletal muscle AMPK signaling in humans. Diabetes 2003; 52(9): 2205–2212. https://doi.org/10.2337/diabetes.52.9.2205.
Léger B, Cartoni R, Praz M, Lamon S, Dériaz O, Crettenand A, et al. Akt signalling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. J Physiol 2006; 576(Pt 3): 923–933. https://doi.org/10.1113/jphysiol.2006.116715.
Bayod S, Del Valle J, Lalanza JF, Sanchez-Roige S, de Luxán-Delgado B, Coto-Montes A, et al. Long-term physical exercise induces changes in sirtuin 1 pathway and oxidative parameters in adult rat tissues. Exp Gerontol 2012; 47(12): 925–935. https://doi.org/10.1016/j.exger.2012.08.004.
Tremblay A, Simoneau JA, Bouchard C. Impact of exercise intensity on body fatness and skeletal muscle metabolism. Metabolism. 1994; 43(7): 814–818. https://doi.org/10.1016/0026-0495(94)90259-3.
Sharples AP, Hughes DC, Deane CS, Saini A, Selman C, Stewart CE. Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake. Aging Cell 2015; 14(4): 511–523. https://doi.org/10.1111/acel.12342.
Flurkey K, McUrrer J, Harrison D. Mouse models in aging research. In: Fox JG, Barthold SW, Davisson MT, Newcomer CE, Quimby FW, Smith AL, editors. The mouse in biomedical research: normative biology, husbandry, and models. Vol. 3. 2nd ed. Amsterdam: Elsevier, Inc.; 2007. p. 637–672. https://doi.org/10.1016/b978-012369454-6/50074-1.
Ikeda K, Horie-Inoue K, Inoue S. Functions of estrogen and estrogen receptor signaling on skeletal muscle. J Steroid Biochem Mol Biol 2019; 191: 105375. https://doi.org/10.1016/j.jsbmb.2019.105375.
Norenberg KM, Fitts RH. Contractile responses of the rat gastrocnemius and soleus muscles to isotonic resistance exercise. J Appl Physiol (1985) 2004; 97(6): 2322–2332. https://doi.org/10.1152/japplphysiol.00955.2003.
Terada S, Tabata I. Effects of acute bouts of running and swimming exercise on PGC-1α protein expression in rat epitrochlearis and soleus muscle. Am J Physiol Endocrinol Metab 2004; 286(2):E208–E216. https://doi.org/10.1152/ajpendo.00051.2003.
Aksamitiene E, Hoek JB, Kholodenko B, Kiyatkin A. Multistrip Western blotting to increase quantitative data output. Electrophoresis 2007; 28(18): 3163–3173. https://doi.org/10.1002/elps.200700002.
Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007; 39(2): 175–191. https://doi.org/10.3758/BF03193146.
Chen C, Zhou M, Ge Y, Wang X. SIRT1 and aging related signaling pathways. Mech Ageing Dev 2020; 187: 111215. https://doi.org/10.1016/j.mad.2020.111215.
Gurd BJ, Yoshida Y, McFarlan JT, Holloway GP, Moyes CD, Heigenhauser GJF, et al. Nuclear SIRT1 activity, but not protein content, regulates mitochondrial biogenesis in rat and human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 2011; 301(1): R67–R75. https://doi.org/10.1152/ajpregu.00417.2010.
Huang C-C, Wang T, Tung Y-T, Lin W-T. Effect of exercise training on skeletal muscle SIRT1 and PGC-1α expression levels in rats of different age. Int J Med Sci 2016; 13(4): 260–270. https://doi.org/10.7150/ijms.14586.
Kjøbsted R, Hingst JR, Fentz J, Foretz M, Sanz M-N, Pehmøller C, et al. AMPK in skeletal muscle function and metabolism. FASEB J 2018; 32(4): 1741–1777. https://doi.org/10.1096/fj.201700442R.
Atherton PJ, Babraj J, Smith K, Singh J, Rennie MJ, Wackerhage H. Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. FASEB J 2005; 19(7): 786–788. https://doi.org/10.1096/fj.04-2179fje.
Bae JY. Resistance exercise regulates hepatic lipolytic factors as effective as aerobic exercise in obese mice. Int J Environ Res Public Health 2020; 17(22): 8307. https://doi.org/10.3390/ijerph17228307.
Tang L, Cao W, Zhao T, Yu K, Sun L, Guo J, et al. Weight-bearing exercise prevents skeletal muscle atrophy in ovariectomized rats. J Physiol Biochem 2021; 77(2): 273–281. https://doi.org/10.1007/s13105-021-00794-0.
Markofski MM, Dickinson JM, Drummond MJ, Fry CS, Fujita S, Gundermann DM, et al. Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women. Exp Gerontol 2015; 65: 1–7. https://doi.org/10.1016/j.exger.2015.02.015.
Zeng Z, Liang J, Wu L, Zhang H, Lv J, Chen N. Exercise-induced autophagy suppresses sarcopenia through Akt/mTOR and Akt/FoxO3a signal pathways and AMPK-mediated mitochondrial quality control. Front Physiol 2020; 11: 583478. https://doi.org/10.3389/fphys.2020.583478.
You J-S, McNally RM, Jacobs BL, Privett RE, Gundermann DM, Lin K-H, et al. The role of raptor in the mechanical load-induced regulation of mTOR signaling, protein synthesis, and skeletal muscle hypertrophy. FASEB J 2019; 33(3): 4021–4034. https://doi.org/10.1096/fj.201801653RR.
Williamson D, Gallagher P, Harber M, Hollon C, Trappe S. Mitogen-activated protein kinase (MAPK) pathway activation: effects of age and acute exercise on human skeletal muscle. J Physiol 2003; 547(Pt 3): 977–987. https://doi.org/10.1113/jphysiol.2002.036673.