REFERENCES
1. Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics-2021 update: a report from the american heart association. Circulation 2021;143:e254-743.
2. Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics-2022 update: a report from the american heart association. Circulation 2022;145:e153-639.
3. Jousilahti P, Vartiainen E, Tuomilehto J, Puska P. Sex, age, cardiovascular risk factors, and coronary heart disease: a prospective follow-up study of 14 786 middle-aged men and women in Finland. Circulation 1999;99:1165-72.
7. Cruz-Jentoft AJ. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019;48:16-31.
8. Bekfani T, Pellicori P, Morris DA, et al. Sarcopenia in patients with heart failure with preserved ejection fraction: Impact on muscle strength, exercise capacity and quality of life. Int J Cardiol 2016;222:41-6.
9. Emami A, Saitoh M, Valentova M, et al. Comparison of sarcopenia and cachexia in men with chronic heart failure: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). Eur J Heart Fail 2018;20:1580-7.
10. Streng KW, Nauta JF, Hillege HL, et al. Non-cardiac comorbidities in heart failure with reduced, mid-range and preserved ejection fraction. Int J Cardiol 2018;271:132-9.
11. Tucker WJ, Haykowsky MJ, Seo Y, Stehling E, Forman DE. Impaired exercise tolerance in heart failure: role of skeletal muscle morphology and function. Curr Heart Fail Rep 2018;15:323-31.
13. Haehling S, Ebner N, Dos Santos MR, Springer J, Anker SD. Muscle wasting and cachexia in heart failure: mechanisms and therapies. Nat Rev Cardiol 2017;14:323-41.
14. Biagi E, Franceschi C, Rampelli S, et al. Gut microbiota and extreme longevity. Curr Biol 2016;26:1480-5.
15. Coats AJ, Clark AL, Piepoli M, Volterrani M, Poole-Wilson PA. Symptoms and quality of life in heart failure: the muscle hypothesis. Br Heart J 1994;72:S36-9.
16. Murphy KT. The pathogenesis and treatment of cardiac atrophy in cancer cachexia. Am J Physiol Heart Circ Physiol 2016;310:H466-77.
17. Sweeney M, Yiu A, Lyon AR. Cardiac atrophy and heart failure in cancer. Cardiac Failure Rev 2017;03:62.
18. Brand JS, Rovers MM, Yeap BB, et al. Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: an individual participant data meta-analysis of observational studies. PLoS One 2014;9:e100409.
19. Jankowska EA, Filippatos G, Ponikowska B, et al. Reduction in circulating testosterone relates to exercise capacity in men with chronic heart failure. J Card Fail 2009;15:442-50.
20. Pugh P. Acute haemodynamic effects of testosterone in men with chronic heart failure. Eur Heart J 2003;24:909-15.
21. Pugh PJ, Jones RD, West JN, Jones TH, Channer KS. Testosterone treatment for men with chronic heart failure. Heart 2004;90:446-7.
22. Malkin CJ, Pugh PJ, West JN, van Beek EJ, Jones TH, Channer KS. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Eur Heart J 2006;27:57-64.
23. Caminiti G, Volterrani M, Iellamo F, et al. Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol 2009;54:919-27.
24. Iellamo F, Volterrani M, Caminiti G, et al. Testosterone therapy in women with chronic heart failure: a pilot double-blind, randomized, placebo-controlled study. J Am Coll Cardiol 2010;56:1310-6.
25. Wilson C, Contreras-Ferrat A, Venegas N, et al. Testosterone increases GLUT4-dependent glucose uptake in cardiomyocytes. J Cell Physiol 2013;228:2399-407.
26. Wu Y, Bauman WA, Blitzer RD, Cardozo C. Testosterone-induced hypertrophy of L6 myoblasts is dependent upon Erk and mTOR. Biochem Biophys Res Commun 2010;400:679-83.
27. Basualto-Alarcón C, Jorquera G, Altamirano F, Jaimovich E, Estrada M. Testosterone signals through mTOR and androgen receptor to induce muscle hypertrophy. Med Sci Sports Exerc 2013;45:1712-20.
28. Egerman MA, Glass DJ. Signaling pathways controlling skeletal muscle mass. Crit Rev Biochem Mol Biol 2014;49:59-68.
29. Rommel C, Bodine SC, Clarke BA, et al. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol 2001;3:1009-13.
30. Sacheck JM, Ohtsuka A, McLary SC, Goldberg AL. IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Am J Physiol Endocrinol Metab 2004;287:E591-601.
31. Haddad F, Adams GR. Inhibition of MAP/ERK kinase prevents IGF-I-induced hypertrophy in rat muscles. J Appl Physiol (1985) 2004;96:203-10.
32. Stitt TN, Drujan D, Clarke BA, et al. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Molecular Cell 2004;14:395-403.
33. Lee SJ, McPherron AC. Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci USA 2001;98:9306-11.
34. McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 1997;387:83-90.
35. George I, Bish LT, Kamalakkannan G, et al. Myostatin activation in patients with advanced heart failure and after mechanical unloading. Eur J Heart Fail 2010;12:444-53.
36. Gruson D, Ahn SA, Ketelslegers JM, Rousseau MF. Increased plasma myostatin in heart failure. Eur J Heart Fail 2011;13:734-6.
37. Lima AR, Martinez PF, Okoshi K, et al. Myostatin and follistatin expression in skeletal muscles of rats with chronic heart failure. Int J Exp Pathol 2010;91:54-62.
38. Rock KL, Gramm C, Rothstein L, et al. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 1994;78:761-71.
40. Bonaldo P, Sandri M. Cellular and molecular mechanisms of muscle atrophy. Dis Model Mech 2013;6:25-39.
41. Schiaffino S, Hanzlíkovávěra. Studies on the effect of denervation in developing muscle. II. The lysosomal system. J Ultrastruct Res 1972;39:1-14.
42. Furuno K, Goodman MN, Goldberg AL. Role of different proteolytic systems in the degradation of muscle proteins during denervation atrophy. J Biol Chem 1990;265:8550-7.
43. García-Prat L, Martínez-Vicente M, Perdiguero E, et al. Autophagy maintains stemness by preventing senescence. Nature 2016;529:37-42.
44. Sousa-Victor P, Gutarra S, García-Prat L, et al. Geriatric muscle stem cells switch reversible quiescence into senescence. Nature 2014;506:316-21.
45. Deval C, Mordier S, Obled C, et al. Identification of cathepsin L as a differentially expressed message associated with skeletal muscle wasting. Biochem J 2001;360:143.
46. Mammucari C, Milan G, Romanello V, et al. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab 2007;6:458-71.
47. Dobrowolny G, Aucello M, Rizzuto E, et al. Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab 2008;8:425-36.
48. Lecker SH, Jagoe RT, Gilbert A, et al. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J 2004;18:39-51.
49. Adams V, Jiang H, Yu J, et al. Apoptosis in skeletal myocytes of patients with chronic heart failure is associated with exercise intolerance. J Am College Cardiol 1999;33:959-65.
50. Vescovo G, Volterrani M, Zennaro R, et al. Apoptosis in the skeletal muscle of patients with heart failure: investigation of clinical and biochemical changes. Heart 2000;84:431-7.
51. Libera LD, Zennaro R, Sandri M, Ambrosio GB, Vescovo G. Apoptosis and atrophy in rat slow skeletal muscles in chronic heart failure. Am J Physiol 1999;277:C982-6.
52. Mitchell RG, Duscha BD, Robbins JL, et al. Increased levels of apoptosis in gastrocnemius skeletal muscle in patients with peripheral arterial disease. Vasc Med 2007;12:285-90.
53. Schaap LA, Pluijm SM, Deeg DJ, et al. Higher inflammatory marker levels in older persons: associations with 5-year change in muscle mass and muscle strength. J Gerontol A Biol Sci Med Sci 2009;64:1183-9.
54. Tuttle CSL, Thang LAN, Maier AB. Markers of inflammation and their association with muscle strength and mass: a systematic review and meta-analysis. Ageing Res Rev 2020;64:101185.
55. Dalla Libera L, Sabbadini R, Renken C, et al. Apoptosis in the skeletal muscle of rats with heart failure is associated with increased serum levels of TNF-alpha and sphingosine. J Mol Cell Cardiol 2001;33:1871-8.
56. Okutsu M, Call JA, Lira VA, et al. Extracellular superoxide dismutase ameliorates skeletal muscle abnormalities, cachexia, and exercise intolerance in mice with congestive heart failure. Circ Heart Fail 2014;7:519-30.
57. Allard MF, Schönekess BO, Henning SL, English DR, Lopaschuk GD. Contribution of oxidative metabolism and glycolysis to ATP production in hypertrophied hearts. Am J Physiol 1994;267:H742-50.
58. Zhu Q, Gao R, Zhang Y, et al. Dysbiosis signatures of gut microbiota in coronary artery disease. Physiol Genomics 2018;50:893-903.
59. Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol 2021;19:55-71.
60. Tang WH, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013;368:1575-84.
61. Luedde M, Winkler T, Heinsen FA, et al. Heart failure is associated with depletion of core intestinal microbiota. ESC Heart Fail 2017;4:282-90.
62. Beale AL, O’Donnell JA, Nakai ME, et al. The gut microbiome of heart failure with preserved ejection fraction. J Am Heart Assoc 2021;10:e020654.
63. Tang WHW, Li DY, Hazen SL. Dietary metabolism, the gut microbiome, and heart failure. Nat Rev Cardiol 2019;16:137-54.
64. Niebauer J, Volk H, Kemp M, et al. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet 1999;353:1838-42.
65. Buffa JA, Romano KA, Copeland MF, et al. The microbial gbu gene cluster links cardiovascular disease risk associated with red meat consumption to microbiota L-carnitine catabolism. Nat Microbiol 2022;7:73-86.
66. Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013;19:576-85.
67. Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011;472:57-63.
68. Zhu W, Gregory JC, Org E, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 2016;165:111-24.
69. Tan Y, Zhou J, Liu C, et al. Association between plasma trimethylamine n-oxide and neoatherosclerosis in patients with very late stent thrombosis. Can J Cardiol 2020;36:1252-60.
70. Tan Y, Sheng Z, Zhou P, et al. Plasma trimethylamine N-oxide as a novel biomarker for plaque rupture in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv 2019;12:e007281.
71. Li XS, Obeid S, Klingenberg R, et al. Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: a prognostic marker for incident cardiovascular events beyond traditional risk factors. Eur Heart J 2017;38:814-24.
72. Li XS, Wang Z, Cajka T, et al. Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk. JCI Insight 2018;3:99096.
73. Al-Obaide MAI, Singh R, Datta P, et al. Gut microbiota-dependent trimethylamine-N-oxide and serum biomarkers in patients with T2DM and advanced CKD. J Clin Med 2017;6:86.
74. Chen S, Henderson A, Petriello MC, et al. Trimethylamine N-oxide binds and activates perk to promote metabolic dysfunction. Cell Metab 2019;30:1141-1151.e5.
75. Ufnal M, Jazwiec R, Dadlez M, Drapala A, Sikora M, Skrzypecki J. Trimethylamine-N-oxide: a carnitine-derived metabolite that prolongs the hypertensive effect of angiotensin II in rats. Can J Cardiol 2014;30:1700-5.
76. Li T, Chen Y, Gua C, Li X. Elevated circulating trimethylamine N-oxide levels contribute to endothelial dysfunction in aged rats through vascular inflammation and oxidative stress. Front Physiol 2017;8:350.
77. Brunt VE, Gioscia-Ryan RA, Casso AG, et al. Trimethylamine-N-Oxide promotes age-related vascular oxidative stress and endothelial dysfunction in mice and healthy humans. Hypertension 2020;76:101-12.
78. Krauss RM, Eckel RH, Howard B, et al. AHA dietary guidelines: revision 2000: a statement for healthcare professionals from the nutrition committee of the american heart association. Circulation 2000;102:2284-99.
79. Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev 2001;81:1031-64.
81. Brown AJ, Goldsworthy SM, Barnes AA, et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 2003;278:11312-9.
82. Kaisar MMM, Pelgrom LR, van der Ham AJ, Yazdanbakhsh M, Everts B. Butyrate conditions human dendritic cells to prime type 1 regulatory t cells via both histone deacetylase inhibition and g protein-coupled receptor 109a signaling. Front Immunol 2017;8:1429.
83. Pluznick JL, Protzko RJ, Gevorgyan H, et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci USA 2013;110:4410-5.
84. Ang Z, Er JZ, Tan NS, et al. Human and mouse monocytes display distinct signalling and cytokine profiles upon stimulation with FFAR2/FFAR3 short-chain fatty acid receptor agonists. Sci Rep 2016;6:34145.
85. Masui R, Sasaki M, Funaki Y, et al. G protein-coupled receptor 43 moderates gut inflammation through cytokine regulation from mononuclear cells. Inflamm Bowel Dis 2013;19:2848-56.
86. Huang W, Man Y, Gao C, et al. Short-chain fatty acids ameliorate diabetic nephropathy via GPR43-mediated inhibition of oxidative stress and NF-. κ ;2020:4074832.
87. Lee SU, In HJ, Kwon MS, et al. β-Arrestin 2 mediates G protein-coupled receptor 43 signals to nuclear factor-κB. Biol Pharm Bull 2013;36:1754-9.
88. Marques FZ, Nelson E, Chu PY, et al. High-Fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice. Circulation 2017;135:964-77.
89. Zhang L, Deng M, Lu A, et al. Sodium butyrate attenuates angiotensin II-induced cardiac hypertrophy by inhibiting COX2/PGE2 pathway via a HDAC5/HDAC6-dependent mechanism. J Cell Mol Med 2019;23:8139-50.
90. Liu CF, Tang WHW. Epigenetics in cardiac hypertrophy and heart failure. JACC Basic Transl Sci 2019;4:976-93.
91. Li M, van Esch BCAM, Henricks PAJ, Folkerts G, Garssen J. The Anti-inflammatory Effects of short chain fatty acids on lipopolysaccharide- or tumor necrosis factor α-stimulated endothelial cells via activation of GPR41/43 and Inhibition of HDACs. Front Pharmacol 2018;9:533.
92. Chang PV, Hao L, Offermanns S, Medzhitov R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci USA 2014;111:2247-52.
93. Brown JM, Hazen SL. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases. Annu Rev Med 2015;66:343-59.
94. Astrup A, Magkos F, Bier DM, et al. Saturated fats and health: a reassessment and proposal for food-based recommendations: JACC state-of-the-art review. J Am Coll Cardiol 2020;76:844-57.
95. Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem 2003;72:137-74.
96. Ridlon JM, Kang DJ, Hylemon PB. Bile salt biotransformations by human intestinal bacteria. J Lipid Res 2006;47:241-59.
97. Staels B, Fonseca VA. Bile acids and metabolic regulation: mechanisms and clinical responses to bile acid sequestration. Diabetes Care 2009;32 Suppl 2:S237-45.
98. Watanabe M, Houten SM, Mataki C, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006;439:484-9.
99. Binah O, Rubinstein I, Bomzon A, Better OS. Effects of bile acids on ventricular muscle contraction and electrophysiological properties: studies in rat papillary muscle and isolated ventricular myocytes. Naunyn Schmiedebergs Arch Pharmacol 1987;335:160-5.
100. Bogin E, Better O, Harari I. The effect of jaundiced sera and bile salts on cultured beating rat heart cells. Experientia 1983;39:1307-8.
101. Sheikh Abdul Kadir SH, Miragoli M, Abu-Hayyeh S, et al. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes. PLoS One 2010;5:e9689.
102. Williamson C, Gorelik J, Eaton BM, Lab M, Swiet MD, Korchev Y. The bile acid taurocholate impairs rat cardiomyocyte function: a proposed mechanism for intra-uterine fetal death in obstetric cholestasis. Clin Sci 2001;100:363-9.
103. Gorelik J, Harding SE, Shevchuk AI, et al. Taurocholate induces changes in rat cardiomyocyte contraction and calcium dynamics. Clin Sci (Lond) 2002;103:191-200.
104. Desai MS, Mathur B, Eblimit Z, et al. Bile acid excess induces cardiomyopathy and metabolic dysfunctions in the heart. Hepatology 2017;65:189-201.
105. Mayerhofer CCK, Ueland T, Broch K, et al. Increased secondary/primary bile acid ratio in chronic heart failure. J Card Fail 2017;23:666-71.
106. Ebner N, Anker SD, von Haehling S. Recent developments in the field of cachexia, sarcopenia, and muscle wasting: highlights from the 11th Cachexia Conference. J Cachexia Sarcopenia Muscle 2019;10:218-25.
107. Toney AM, Fox D, Chaidez V, Ramer-Tait AE, Chung S. Immunomodulatory role of urolithin a on metabolic diseases. Biomedicines 2021;9:192.
108. Zanotti I, Dall’Asta M, Mena P, et al. Atheroprotective effects of (poly)phenols: a focus on cell cholesterol metabolism. Food Funct 2015;6:13-31.
109. García-Mantrana I, Calatayud M, Romo-Vaquero M, Espín JC, Selma MV, Collado MC. Urolithin metabotypes can determine the modulation of gut microbiota in healthy individuals by tracking walnuts consumption over three days. Nutrients 2019;11:2483.
110. Savi M, Bocchi L, Mena P, et al. In vivo administration of urolithin A and B prevents the occurrence of cardiac dysfunction in streptozotocin-induced diabetic rats. Cardiovasc Diabetol 2017;16:80.
111. Tang L, Mo Y, Li Y, et al. Urolithin A alleviates myocardial ischemia/reperfusion injury via PI3K/Akt pathway. Biochem Biophys Res Commun 2017;486:774-80.
112. Ghosh N, Das A, Biswas N, et al. Urolithin A augments angiogenic pathways in skeletal muscle by bolstering NAD+ and SIRT1. Sci Rep 2020;10:20184.
113. Nemet I, Saha PP, Gupta N, et al. A Cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors. Cell 2020;180:862-877.e22.
114. Melamed ML, Plantinga L, Shafi T, et al. Retained organic solutes, patient characteristics and all-cause and cardiovascular mortality in hemodialysis: results from the retained organic solutes and clinical outcomes (ROSCO) investigators. BMC Nephrol 2013;14:134.
115. Wu IW, Hsu KH, Hsu HJ, et al. Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients--a prospective cohort study. Nephrol Dial Transplant 2012;27:1169-75.
116. Lin CJ, Pan CF, Liu HL, et al. The role of protein-bound uremic toxins on peripheral artery disease and vascular access failure in patients on hemodialysis. Atherosclerosis 2012;225:173-9.
117. Huang ST, Shu KH, Cheng CH, et al. Serum total p-cresol and indoxyl sulfate correlated with stage of chronic kidney disease in renal transplant recipients. Transplant Proc 2012;44:621-4.
118. Lekawanvijit S, Adrahtas A, Kelly DJ, Kompa AR, Wang BH, Krum H. Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes? Eur Heart J 2010;31:1771-9.
119. Yisireyili M, Shimizu H, Saito S, Enomoto A, Nishijima F, Niwa T. Indoxyl sulfate promotes cardiac fibrosis with enhanced oxidative stress in hypertensive rats. Life Sci 2013;92:1180-5.
120. Peng YS, Ding HC, Lin YT, Syu JP, Chen Y, Wang SM. Uremic toxin p-cresol induces disassembly of gap junctions of cardiomyocytes. Toxicology 2012;302:11-7.
121. Han H, Zhu J, Zhu Z, et al. p-Cresyl sulfate aggravates cardiac dysfunction associated with chronic kidney disease by enhancing apoptosis of cardiomyocytes. J Am Heart Assoc 2015;4:e001852.
122. Six I, Flissi N, Lenglet G, et al. Uremic toxins and vascular dysfunction. Toxins (Basel) 2020;12:404.
123. Lv J, Chen J, Wang M, Yan F. Klotho alleviates indoxyl sulfate-induced heart failure and kidney damage by promoting M2 macrophage polarization. Aging (Albany NY) 2020;12:9139-50.
124. Chen K, Wang S, Sun QW, Zhang B, Ullah M, Sun Z. Klotho deficiency causes heart aging via impairing the Nrf2-GR pathway. Circ Res 2021;128:492-507.
125. Siddharth J, Chakrabarti A, Pannérec A, et al. Aging and sarcopenia associate with specific interactions between gut microbes, serum biomarkers and host physiology in rats. Aging (Albany NY) 2017;9:1698-720.
126. Bindels LB, Beck R, Schakman O, et al. Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model. PLoS One 2012;7:e37971.
127. Munukka E, Rintala A, Toivonen R, et al. Faecalibacterium prausnitzii treatment improves hepatic health and reduces adipose tissue inflammation in high-fat fed mice. ISME J 2017;11:1667-79.
128. Varian BJ, Goureshetti S, Poutahidis T, et al. Beneficial bacteria inhibit cachexia. Oncotarget 2016;7:11803-16.
129. Walsh ME, Bhattacharya A, Sataranatarajan K, et al. The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging. Aging Cell 2015;14:957-70.
130. Wu CS, Wei Q, Wang H, et al. Protective effects of ghrelin on fasting-induced muscle atrophy in aging mice. J Gerontol A Biol Sci Med Sci 2020;75:621-30.
131. Lustgarten MS. The Role of the gut microbiome on skeletal muscle mass and physical function: 2019 update. Front Physiol 2019;10:1435.
132. Abrigo J, Campos F, Gonzalez F, et al. Sarcopenia Induced by chronic liver disease in mice requires the expression of the bile acids membrane receptor TGR5. Int J Mol Sci 2020;21:7922.
133. Thibaut MM, Sboarina M, Roumain M, et al. Inflammation-induced cholestasis in cancer cachexia. J Cachexia Sarcopenia Muscle 2021;12:70-90.
134. He W, Luo Y, Liu J, et al. Trimethylamine N-Oxide, a gut microbiota-dependent metabolite, is associated with frailty in older adults with cardiovascular disease. CIA 2020;15:1809-20.
135. Enoki Y, Watanabe H, Arake R, et al. Indoxyl sulfate potentiates skeletal muscle atrophy by inducing the oxidative stress-mediated expression of myostatin and atrogin-1. Sci Rep 2016;6:32084.
136. Rodrigues GGC, Dellê H, Brito RBO, et al. Indoxyl sulfate contributes to uremic sarcopenia by inducing apoptosis in myoblasts. Arch Med Res 2020;51:21-9.
137. Sato E, Mori T, Mishima E, et al. Metabolic alterations by indoxyl sulfate in skeletal muscle induce uremic sarcopenia in chronic kidney disease. Sci Rep 2016;6:36618.
138. Picca A, Ponziani FR, Calvani R, et al. Gut microbial, inflammatory and metabolic signatures in older people with physical frailty and sarcopenia: results from the biosphere study. Nutrients 2019;12:65.
139. Buigues C, Fernández-Garrido J, Pruimboom L, et al. Effect of a prebiotic formulation on frailty syndrome: a randomized, double-blind clinical trial. Int J Mol Sci 2016;17:932.
140. Aoyagi Y, Amamoto R, Park S, et al. Independent and interactive effects of habitually ingesting fermented milk products containing lactobacillus casei strain shirota and of engaging in moderate habitual daily physical activity on the intestinal health of older people. Front Microbiol 2019;10:1477.
141. Ferrari R, Cargnoni A, Ceconi C. Anti-ischaemic effect of ivabradine. Pharmacol Res 2006;53:435-9.
142. Griffiths EJ, Rutter GA. Mitochondrial calcium as a key regulator of mitochondrial ATP production in mammalian cells. Biochim Biophys Acta 2009;1787:1324-33.
143. Rizzuto R, De Stefani D, Raffaello A, Mammucari C. Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol 2012;13:566-78.
144. Coen PM, Musci RV, Hinkley JM, Miller BF. Mitochondria as a Target for Mitigating Sarcopenia. Front Physiol 2018;9:1883.
145. Chaudhary KR, El-Sikhry H, Seubert JM. Mitochondria and the aging heart. J Geriatr Cardiol 2011;8:159-67.
146. Gonzalez-Freire M, Scalzo P, D’Agostino J, et al. Skeletal muscle ex vivo mitochondrial respiration parallels decline in vivo oxidative capacity, cardiorespiratory fitness, and muscle strength: The Baltimore Longitudinal Study of Aging. Aging Cell 2018;17:e12725.
147. Lai L, Leone TC, Keller MP, et al. Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach. Circ Heart Fail 2014;7:1022-31.
148. Tezze C, Romanello V, Desbats MA, et al. Age-associated loss of OPA1 in muscle impacts muscle mass, metabolic homeostasis, systemic inflammation, and epithelial senescence. Cell Metab 2017;25:1374-1389.e6.
149. Sebastián D, Sorianello E, Segalés J, et al. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway. EMBO J 2016;35:1677-93.
150. Leduc-Gaudet JP, Hussain SNA, Barreiro E, Gouspillou G. Mitochondrial dynamics and mitophagy in skeletal muscle health and aging. Int J Mol Sci 2021;22:8179.
151. Casuso RA, Huertas JR. The emerging role of skeletal muscle mitochondrial dynamics in exercise and ageing. Ageing Res Rev 2020;58:101025.
152. Li YP, Chen Y, Li AS, Reid MB. Hydrogen peroxide stimulates ubiquitin-conjugating activity and expression of genes for specific E2 and E3 proteins in skeletal muscle myotubes. Am J Physiol Cell Physiol 2003;285:C806-12.
153. Aucello M, Dobrowolny G, Musaro A. Localized accumulation of oxidative stress causes muscle atrophy through activation of an autophagic pathway. Autophagy 2009;5:527-9.
154. Romanello V, Guadagnin E, Gomes L, et al. Mitochondrial fission and remodelling contributes to muscle atrophy. EMBO J 2010;29:1774-85.
155. Salminen A, Ojala J, Kaarniranta K, Kauppinen A. Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases. Cell Mol Life Sci 2012;69:2999-3013.
156. Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 2004;18:357-68.
157. Finck BN, Kelly DP. PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 2006;116:615-22.
158. Arany Z, He H, Lin J, et al. Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab 2005;1:259-71.
159. Viña J, Gomez-Cabrera MC, Borras C, et al. Mitochondrial biogenesis in exercise and in ageing. Adv Drug Deliv Rev 2009;61:1369-74.
160. Dillon LM, Rebelo AP, Moraes CT. The role of PGC-1 coactivators in aging skeletal muscle and heart. IUBMB Life 2012;64:231-41.
161. Migliavacca E, Tay SKH, Patel HP, et al. Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities. Nat Commun 2019;10:5808.
162. Kong X, Wang R, Xue Y, et al. Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS One 2010;5:e11707.
163. Joseph AM, Adhihetty PJ, Buford TW, et al. The impact of aging on mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high- and low-functioning elderly individuals. Aging Cell 2012;11:801-9.
164. Liu HW, Chang YC, Chan YC, Hu SH, Liu MY, Chang SJ. Dysregulations of mitochondrial quality control and autophagic flux at an early age lead to progression of sarcopenia in SAMP8 mice. Biogerontology 2020;21:367-80.
165. Lahiri S, Kim H, Garcia-Perez I, et al. The gut microbiota influences skeletal muscle mass and function in mice. Sci Transl Med 2019;11:eaan5662.
166. Ryu D, Mouchiroud L, Andreux PA, et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat Med 2016;22:879-88.
167. Makrecka-Kuka M, Volska K, Antone U, et al. Trimethylamine N-oxide impairs pyruvate and fatty acid oxidation in cardiac mitochondria. Toxicol Lett 2017;267:32-8.
168. Vaiserman AM, Koliada AK, Marotta F. Gut microbiota: A player in aging and a target for anti-aging intervention. Ageing Res Rev 2017;35:36-45.
169. Buford TW. (Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease. Microbiome 2017;5:80.
170. Harber MP, Konopka AR, Undem MK, et al. Aerobic exercise training induces skeletal muscle hypertrophy and age-dependent adaptations in myofiber function in young and older men. J Appl Physiol (1985) 2012;113:1495-504.
171. Konopka AR, Harber MP. Skeletal muscle hypertrophy after aerobic exercise training. Exerc Sport Sci Rev 2014;42:53-61.
172. Bori Z, Zhao Z, Koltai E, et al. The effects of aging, physical training, and a single bout of exercise on mitochondrial protein expression in human skeletal muscle. Exp Gerontol 2012;47:417-24.
173. Johnston AP, De Lisio M, Parise G. Resistance training, sarcopenia, and the mitochondrial theory of aging. Appl Physiol Nutr Metab 2008;33:191-9.
174. Clarke SF, Murphy EF, O’Sullivan O, et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 2014;63:1913-20.
175. Taniguchi H, Tanisawa K, Sun X, et al. Effects of short-term endurance exercise on gut microbiota in elderly men. Physiol Rep 2018;6:e13935.
176. Munukka E, Ahtiainen JP, Puigbó P, et al. Six-week endurance exercise alters gut metagenome that is not reflected in systemic metabolism in over-weight women. Front Microbiol 2018;9:2323.
177. Šoltys K, Lendvorský L, Hric I, et al. Strenuous physical training, physical fitness, body composition and bacteroides to prevotella ratio in the gut of elderly athletes. Front Physiol 2021;12:670989.
178. Perry CA, Gadde KM. The role of calorie restriction in the prevention of cardiovascular disease. Curr Atheroscler Rep 2022;24:235-42.
179. Li L, Su Y, Li F, et al. The effects of daily fasting hours on shaping gut microbiota in mice. BMC Microbiol 2020;20:65.
180. van der Merwe M, Sharma S, Caldwell JL, et al. Time of feeding alters obesity-associated parameters and gut bacterial communities, but not fungal populations, in C57BL/6 male mice. Curr Dev Nutr 2020;4:nzz145.
181. Beli E. Restructuring of the gut microbiome by intermittent fasting prevents retinopathy and prolongs survival in db/db mice. Diabetes 2018;67:1867-79.
182. Cignarella F, Cantoni C, Ghezzi L, et al. Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota. Cell Metab 2018;27:1222-1235.e6.
183. Fraumene C. Caloric restriction promotes rapid expansion and long-lasting increase of Lactobacillus in the rat fecal microbiota. Gut Microbes 2018;9:104-114.
184. Nagata S, Asahara T, Ohta T, et al. Effect of the continuous intake of probiotic-fermented milk containing Lactobacillus casei strain Shirota on fever in a mass outbreak of norovirus gastroenteritis and the faecal microflora in a health service facility for the aged. Br J Nutr 2011;106:549-56.
185. Akatsu H, Iwabuchi N, Xiao JZ, et al. Clinical effects of probiotic Bifidobacterium longum BB536 on immune function and intestinal microbiota in elderly patients receiving enteral tube feeding. JPEN J Parenter Enteral Nutr 2013;37:631-40.
186. Ostan R, Béné MC, Spazzafumo L, et al. Impact of diet and nutraceutical supplementation on inflammation in elderly people. Results from the RISTOMED study, an open-label randomized control trial. Clin Nutr 2016;35:812-8.
187. Nagata S, Asahara T, Wang C, et al. The Effectiveness of lactobacillus beverages in controlling infections among the residents of an aged care facility: a randomized placebo-controlled double-blind trial. Ann Nutr Metab 2016;68:51-9.