Abstract
Regular exercise is an important part of a healthy lifestyle, as it helps maintain a healthy weight and reduces the risk of chronic diseases. We explored the effects of lifelong exercise and aging on rat metabolism through a metabolomics approach. Thirty-six rats were divided into four equal groups: exercise during the 1st half of life (3–12 months), lifelong exercise (3–21 months), no exercise, and exercise during the 2nd half of life (12–21 months). Exercise consisted in swimming for 20 min, five times a week. Blood samples collected at 3, 12, and 21 months of life were analysed by 1H NMR spectroscopy. The groups that exercised during the 2nd half of life weighed less than the groups that did not. Exercise had an orexigenic effect during the 1st half and an anorexigenic effect during the 2nd half. Multivariate analysis showed a clear discrimination between ages when groups were treated as one and between the exercising and non-exercising groups at 12 months. Univariate analysis showed many effects of aging and some effects of exercise on metabolites involved in carbohydrate, lipid and protein metabolism. Especially during the 1st half, exercise had anabolic effects, whereas aging had catabolic effects on amino acid metabolism. In two cases (glycine and succinate), exercise (especially during the 1st half) mitigated potentially harmful effects of aging. The higher values of succinate and the lower values of lactate during the 1st half in the exercising groups suggest increased oxidative metabolism. In conclusion, moderate-intensity exercise for life or half-life had strong and potentially healthful effects on body weight and (partly) appetite, as well as on some blood metabolites. The effects of aging on the rat blood metabolome seemed to be stronger than those of exercise.
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The data that support the findings of this study are available from the corresponding author, AT, upon request.
References
Beard JR, Officer A, De CIA, Sadana R (2016) The world report on ageing and health: a policy framework for healthy ageing. Lancet 387(10033):2145–2154. https://doi.org/10.1016/S0140-6736
Benaki D, Mikros E (2018) NMR-based metabolic profiling procedures for biofluids and cell and tissue extracts. In: Theodoridis G, Gika H, Wilson I (eds) Metabolic profiling, methods in molecular biology, vol 1738. Humana Press, New York. https://doi.org/10.1007/978-1-4939-7643-0_8
Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B 57(1):289–300. https://doi.org/10.2307/2346101
Booth FW, Laye MJ, Roberts MD (2011) Lifetime sedentary living accelerates some aspects of secondary aging. J Appl Physiol 111(5):1497–1504. https://doi.org/10.1152/japplphysiol.00420
Chini EN, Chini CCS, Tarrag MG (2017) NAD and the aging process: role in life, death and everything in between. Mol Cell Endocrinol 455:62–74. https://doi.org/10.1016/j.mce.2016.11.003
Chong J, Soufan O, Li C et al (2018) MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis. Nucleic Acids Res. https://doi.org/10.1093/nar/gky310
Cohen J (1988) Statistical power analysis for the behavioral sciences, vol 2. Lawrence Earlbaum Associates, Hillsdale, NJ
Daskalaki E, Easton C, Watson DG (2014) The application of metabolomic profiling to the effects of physical activity. Curr Metabolomics 2(4):233–263. https://doi.org/10.2174/2213235X03666150211000831
Deda O, Gika HG, Taitzoglou I, Raikos N, Theodoridis G (2017) Impact of exercise and aging on rat urine and blood metabolome. An LC-MS based metabolomics longitudinal study. Metabolites 7(1):1–15. https://doi.org/10.3390/metabo7010010
Fang EF, Hou Y, Demarest TG, Croteau DL, Mattson MP, Bohr VA (2017) NAD+ in aging: molecular mechanisms and translational implications. Trends Mol Med 23(10):899–916. https://doi.org/10.1016/j.molmed.2017.08.001
Forbes SC, Little JP, Candow DG (2012) Exercise and nutritional interventions for improving aging muscle health. Endocrine 42:29–38. https://doi.org/10.1007/s12020-012-9676-1
Gargiulo S, Gamba P, Testa G, Leonarduzzi G, Poli G (2016) The role of oxysterols in vascular ageing. J Physiol 594(8):2095–2113. https://doi.org/10.1113/JP271168
Garvey SM, Russ DW, Skelding MB, Dugle JE, Edens NK (2015) Molecular and metabolomic effects of voluntary running wheel activity on skeletal muscle in late middle-aged rats. Physiol Rep 3(2):1–17. https://doi.org/10.14814/phy2.12319
Goutianos G, Tzioura A, Kyparos A, Paschalis V (2015) The rat adequately reflects human responses to exercise in blood biochemical profile: a comparative study. Physiol Rep 3(2):1–9. https://doi.org/10.14814/phy2.12293
Gries KJ, Raue U, Perkins RK et al (2018) Cardiovascular and skeletal muscle health with lifelong exercise. J Appl Physiol 125(5):1636–1645. https://doi.org/10.1152/japplphysiol.00174
Hansen M, Kennedy BK (2016) Does longer lifespan mean longer healthspan? Trends Cell Biol 26(8):565–568
Heaney LM, Deighton K, Suzuki T (2017) Non-targeted metabolomics in sport and exercise science. J Sports Sci 37(9):959–967. https://doi.org/10.1080/02640414.2017.1305122
Hellsten Y (2016) Limitations of skeletal muscle oxygen supply in ageing. J Physiol 594(8):2259–2260. https://doi.org/10.1113/JP272062
Houtkooper RH, Argmann C, Houten SM et al (2011) The metabolic footprint of aging in mice. Sci Rep 1:1–11. https://doi.org/10.1038/srep00134
Huffman KM, Koves TR, Hubal MJ et al (2014) Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness. Diabetologia 57(11):2282–2295. https://doi.org/10.1007/s00125-014-3343-4
Jackson PA, Pialoux V, Corbett D et al (2016) Promoting brain health through exercise and diet in older adults: a physiological perspective. J Physiol 594(16):4485–4498. https://doi.org/10.1113/JP271270
Kim S, Cheon HS, Song JC, Yun SM, Park SI, Jeon JP (2014) Aging-related changes in mouse serum glycerophospholipid profiles. Osong Pub Health Res Perspect 5(6):345–350. https://doi.org/10.1016/j.phrp.2014.10.002
Klein MS, Shearer J (2016) Metabolomics and type 2 diabetes: translating basic research into clinical application. J Diabetes Res. https://doi.org/10.1155/2016/3898502
Lara B, Salinero JJ, Gutiérrez J et al (2016) Influence of endurance running on calcaneal bone stiffness in male and female runners. Eur J Appl Physiol 116(2):327–333. https://doi.org/10.1007/s00421-015-3285-7
Lazarus NR, Lord JM, Harridge SDR (2018) The relationships and interactions between age, exercise and physiological function. J Physiol. https://doi.org/10.1113/JP277071
Lewis GD, Farrell L, Wood MJ et al (2010) Metabolic signatures of exercise in human plasma. Sci Transl Med 2(33):1–13. https://doi.org/10.1126/scitranslmed.3001006
Mittendorfer B, Klein S (2001) Effect of aging on glucose and lipid metabolism during endurance exercise. Int J Sport Nutr Exerc Metab 11:S86–S91. https://doi.org/10.1123/ijsnem.11.s1.s86
Mougios V (2019) Exercise biochemistry. IL, Human Kinetics, Champaign, p 290
Navas-Enamorado I, Bernier M, Brea-Cxalvo G, de Cabo R (2017) Influence of anaerobic and aerobic exercise on age-related pathways in skeletal muscle. Ageing Res Rev 37:39–52. https://doi.org/10.1016/j.arr.2017.04.005
Pechlivanis A, Kostidis S, Saraslanidis P et al (2010) 1H NMR-based metabonomic investigation of the effect of two different exercise sessions on the metabolic fingerprint of human urine. J Proteome Res 9(12):6405–6416. https://doi.org/10.1021/pr100684t
Pechlivanis A, Kostidis S, Saraslanidis P et al (2013) 1H NMR study on the short- and long-term impact of two training programs of sprint running on the metabolic fingerprint of human serum. J Proteome Res 12(1):470–480. https://doi.org/10.1021/pr300846x
Pechlivanis A, Chrysovalantou A, Veskoukis AS, Kouretas D, Mougios V, Theodoridis GA (2014) GC–MS analysis of blood for the metabonomic investigation of the effects of physical exercise and allopurinol administration on rats. J Chromatogr B 966:127–131. https://doi.org/10.1016/j.jchromb.2014.02.005
Pechlivanis A, Papaioannou KG, Tsalis G, Saraslanidis P, Mougios V, Theodoridis GA (2015) Monitoring the response of the human urinary metabolome to brief maximal exercise by a combination of RP-UPLC-MS and 1H NMR spectroscopy. J Proteome Res 14(11):4610–4622. https://doi.org/10.1021/acs.jproteome.5b00470
Rawson ES, Venezia AC (2011) Use of creatine in the elderly and evidence for effects on cognitive function in young and old. Amino Acids 40:1349–1362. https://doi.org/10.1007/s00726-011-0855-9
Seals DR, Justice JN, Larocca TJ (2016) Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity. J Physiol 594(8):2001–2024. https://doi.org/10.1113/jphysiol.2014.282665
Shimazu T, Hirschey MD, Huang JY, Ho LTY, Verdin E (2010) Acetate metabolism and aging: an emerging connection. Mech Ageing Dev 131(7–8):511–516. https://doi.org/10.1016/j.mad.2010.05.001
Siopi A, Deda O, Manou V et al (2017) Effects of different exercise modes on the urinary metabolic fingerprint of men with and without metabolic syndrome. Metabolites 7(5):1–15. https://doi.org/10.3390/metabo7010005
Siopi A, Deda O, Manou V et al (2019) Comparison of the serum metabolic fingerprint of different exercise modes in men with and without metabolic syndrome. Metabolites 9(116):1–17. https://doi.org/10.3390/metabo9060116
Takeshita H, Horiuchi M, Izumo K et al (2012) Long-term voluntary exercise, representing habitual exercise, lowers visceral fat and alters plasma amino acid levels in mice. Environ Health Prev Med 17(4):275–284. https://doi.org/10.1007/s12199-011-0249-3
Viña J, Rodriguez-Mañas L, Salvador-Pascual A, Tarazona-Santabalbina FJ, Gomez-Cabrera MC (2016) Exercise: the lifelong supplement for healthy ageing and slowing down the onset of frailty. J Physiol 594(8):1989–1999. https://doi.org/10.1113/JP270536
Wishart DS, Feunang YD, Marcu A et al (2018) HMDB 4.0—the human metabolome database for 2018. Nucleic Acids Res. 46(D1):D608–D617. https://doi.org/10.1093/nar/gkx1089
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This work was supported by the IKY Fellowships of Excellence for Postgraduate Studies in Greece—Siemens Program.
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All procedures were in accordance with the European Union regulations for care and use of laboratory animals. Additionally, all procedures were approved by the Department of Rural Economy and Veterinary Medicine, Prefecture of Central Macedonia, Hellenic Republic (Code no. EL54BIO10, Protocol no. 449161/4835).
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Tzimou, A., Benaki, D., Nikolaidis, S. et al. Effects of lifelong exercise and aging on the blood metabolic fingerprint of rats. Biogerontology 21, 577–591 (2020). https://doi.org/10.1007/s10522-020-09871-1
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DOI: https://doi.org/10.1007/s10522-020-09871-1