Anti-inflammatory effects of caloric restriction and caloric restriction mimetics_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Duo , ZHANG Xibing , HAN Lei , SU Qiuming ,  RAN Jianghua

Department of Hepatobiliary and Pancreatic Surgery, Calmete Hospital Affiliated to Kunming Medical University, Kunming 650100, P. R. China;

Corresponding author：

RAN Jianghua, Email: rjh2u@163.com

Keywords：

caloric restriction; caloric restriction mimetics; inflammation

DOI：

10.7507/1007-9424.202303086

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To understand the current research status of calorie restriction and calorie restriction mimetics in inflammatory diseases. Method The literatures about the effect of caloric restriction and caloric restriction mimetics on immune cells, inflammatory responses, and clinical applications were reviewed and analyzed. Results As a dietary therapy, the caloric restriction affected the immune system and function by limiting daily energy intake, regulating cellular metabolic pathways and energy patterns, reducing the inflammatory reaction and improving body symptoms. A growing numbers of attention had been paid in aging, type 2 diabetes, cardiovascular disease, osteoarthritis, neurodegenerative diseases, etc. And it was found that some caloric restriction mimetics such as resveratrol, rapamycin, metformin, etc. could not only achieve similar effects with caloric restriction, but also did not need to strictly restrict diet. Conclisions Although calorie restriction has been studied extensively, there is still no widely accepted and uniform calorie restriction protocol, which is challenging in clinical practice. The development of calorie restriction mimetics, which has similar effects to calorie restriction without requiring strict dietary restriction, is more in line with human physiology and is advantageous to patients. There is a certain understanding how these drugs can prevent inflammation by regulating metabolic pathways, and the relation between them is complex. In future, the knowledge proposed in new field of immunometabolism is preferred to prevent inflammation in age-related diseases, and anti-inflammatory drugs should be reused as a therapeutic option for treatment of age-related diseases.

Citation： WANG Duo, ZHANG Xibing, HAN Lei, SU Qiuming, RAN Jianghua. Anti-inflammatory effects of caloric restriction and caloric restriction mimetics. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(8): 982-987. doi: 10.7507/1007-9424.202303086 Copy

1.	Roe K. An inflammation classification system using cytokine parameters. Scand J Immunol, 2021, 93(2): e12970. doi: 10.1111/sji.12970.
2.	Hillion S, Arleevskaya MI, Blanco P, et al. The innate part of the adaptive immune system. Clin Rev Allergy Immunol, 2020, 58(2): 151-154.
3.	Procaccini C, de Candia P, Russo C, et al. Caloric restriction for the immunometabolic control of human health. Cardiovasc Res, 2023, cvad035. doi: 10.1093/cvr/cvad035.
4.	Aminzadeh-Gohari S, Kofler B, Herzog C. Dietary restriction in senolysis and prevention and treatment of disease. Crit Rev Food Sci Nutr, 2022, 1-27. doi: 10.1080/10408398.2022.2153355.
5.	Zhai J, Kongsberg WH, Pan Y, et al. Caloric restriction induced epigenetic effects on aging. Front Cell Dev Biol, 2023, 10: 1079920.
6.	Geltink RIK, Kyle RL, Pearce EL. Unraveling the complex interplay between T cell metabolism and function. Annu Rev Immunol, 2018, 36: 461-488.
7.	Matarese G, Sanna V, Fontana S, et al. Leptin as a novel therapeutic target for immune intervention. Curr Drug Targets Inflamm Allergy, 2002, 1(1): 13-22.
8.	Van den Bossche J, O’Neill LA, Menon D. Macrophage immunometabolism: where are we (going)?. Trends Immunol, 2017, 38(6): 395-406.
9.	Tzelepis F, Blagih J, Khan N, et al. Mitochondrial cyclophilin D regulates T cell metabolic responses and disease tolerance to tuberculosis. Sci Immunol, 2018, 3(23): eaar4135.
10.	Koeken VACM, van Crevel R, Netea MG. T cell metabolism has evolved to tolerate tuberculosis. Cell Metab, 2018, 28(3): 332-333.
11.	Mercken EM, Crosby SD, Lamming DW, et al. Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile. Aging Cell, 2013, 12(4): 645-651.
12.	Redman LM, Smith SR, Burton JH, et al. Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging. Cell Metab, 2018, 27(4): 805-815.
13.	Kurki E, Shi J, Martonen E, et al. Distinct effects of calorie restriction on adipose tissue cytokine and angiogenesis profiles in obese and lean mice. Nutr Metab (Lond), 2012, 9(1): 64.
14.	Razali N, Hohjoh H, Inazumi T, et al. Induced prostanoid synthesis regulates the balance between Th1- and Th2-producing inflammatory cytokines in the thymus of diet-restricted mice. Biol Pharm Bull, 2020, 43(4): 649-662.
15.	Jordan S, Tung N, Casanova-Acebes M, et al. Dietary intake regulates the circulating inflammatory monocyte pool. Cell, 2019, 178(5): 1102-1114.
16.	Contreras NA, Fontana L, Tosti V, et al. Calorie restriction induces reversible lymphopenia and lymphoid organ atrophy due to cell redistribution. Geroscience, 2018, 40(3): 279-291.
17.	Collins N. Dietary regulation of memory T cells. Int J Mol Sci, 2020, 21(12): 4363.
18.	Zhang J, Zhan Z, Li X, et al. Intermittent fasting protects against Alzheimer’s disease possible through restoring aquaporin-4 polarity. Front Mol Neurosci, 2017, 10: 395.
19.	Bock M, Steffen F, Zipp F, et al. Impact of dietary intervention on serum neurofilament light chain in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm, 2021, 9(1): e1102. doi: 10.1212/NXI.0000000000001102.
20.	Rubovitch V, Pharayra A, Har-Even M, et al. Dietary energy restriction ameliorates cognitive impairment in a mouse model of traumatic brain injury. J Mol Neurosci, 2019, 67(4): 613-621.
21.	Roth GS, Ingram DK. Manipulation of health span and function by dietary caloric restriction mimetics. Ann N Y Acad Sci, 2016, 1363: 5-10.
22.	Pérez-Ortín JE, Mena A, Barba-Aliaga M, et al. Cell volume homeostatically controls the rDNA repeat copy number and rRNA synthesis rate in yeast. PLoS Genet, 2021, 17(4): e1009520.
23.	Cohen HY, Miller C, Bitterman KJ, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science, 2004, 305(5682): 390-392.
24.	Lee HJ, Hong YS, Jun W, et al. Nicotinamide riboside ameliorates hepatic metaflammation by modulating NLRP3 inflammasome in a rodent model of type 2 diabetes. J Med Food, 2015, 18(11): 1207-1213.
25.	Gariani K, Menzies KJ, Ryu D, et al. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice. Hepatology, 2016, 63(4): 1190-1204.
26.	Roboon J, Hattori T, Ishii H, et al. Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide-induced microglial and astrocytic neuroinflammation by increasing NAD. J Neurochem, 2021, 158(2): 311-327.
27.	Wang X, Hu X, Yang Y, et al. Nicotinamide mononucleotide protects against β-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Res, 2016, 1643: 1-9.
28.	Guo X, Tan S, Wang T, et al. NAD⁺ salvage governs mitochondrial metabolism, invigorating natural killer cell antitumor immunity. Hepatology, 2022 Jul 11. doi: 10.1002/hep.32658.
29.	Wei CC, Kong YY, Li GQ, et al. Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway. Sci Rep, 2017, 7(1): 717.
30.	Abolaji AO, Adedara AO, Adie MA, et al. Resveratrol prolongs lifespan and improves 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced oxidative damage and behavioural deficits in Drosophila melanogaster. Biochem Biophys Res Commun, 2018, 503(2): 1042-1048.
31.	Niu W, Wang H, Wang B, et al. Resveratrol improves muscle regeneration in obese mice through enhancing mitochondrial biogenesis. J Nutr Biochem, 2021, 98: 108804.
32.	Nwachukwu JC, Srinivasan S, Bruno NE, et al. Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network. Elife, 2014, 3: e02057.
33.	Park SJ, Ahmad F, Philp A, et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell, 2012, 148(3): 421-433.
34.	Park SY, Lee SW, Kim HY, et al. SIRT1 inhibits differentiation of monocytes to macrophages: amelioration of synovial inflammation in rheumatoid arthritis. J Mol Med (Berl), 2016, 94(8): 921-931.
35.	Totonchi H, Mokarram P, Karima S, et al. Resveratrol promotes liver cell survival in mice liver-induced ischemia-reperfusion through unfolded protein response: a possible approach in liver transplantation. BMC Pharmacol Toxicol, 2022, 23(1): 74.
36.	de Queiroz KB, Dos Santos Fontes Pereira T, Araújo MSS, et al. Resveratrol acts anti-inflammatory and neuroprotective in an infant rat model of pneumococcal meningitis by modulating the Hippocampal miRNome. Mol Neurobiol, 2018, 55(12): 8869-8884.
37.	Yu D, Zhao XY, Meng QP, et al. Resveratrol activates the SIRT1/PGC-1 pathway in mice to improve synaptic-related cognitive impairment after TBI. Brain Res, 2022, 1796: 148109.
38.	Chu H, Li H, Guan X, et al. Resveratrol protects late endothelial progenitor cells from TNF-α-induced inflammatory damage by upregulating Krüppel-like factor-2. Mol Med Rep, 2018, 17(4): 5708-5715.
39.	Triggle CR, Mohammed I, Bshesh K, et al. Metformin: is it a drug for all reasons and diseases?. Metabolism, 2022, 133: 155223.
40.	LaMoia TE, Shulman GI. Cellular and molecular mechanisms of metformin action. Endocr Rev, 2021, 42(1): 77-96.
41.	Zhang J, Huang L, Shi X, et al. Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK/NLRP3 inflammasome pathway. Aging (Albany NY), 2020, 12(23): 24270-24287.
42.	Xian H, Liu Y, Rundberg Nilsson A, et al. Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation. Immunity, 2021, 54(7): 1463-1477.
43.	Zhao Y, Zhao Y, Tian Y, et al. Metformin suppresses foam cell formation, inflammation and ferroptosis via the AMPK/ERK signaling pathway in ox-LDL-induced THP-1 monocytes. Exp Ther Med, 2022, 24(4): 636.
44.	Cheng D, Xu Q, Wang Y, et al. Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling. J Transl Med, 2021, 19(1): 349.
45.	Zhang J, Brown R, Hogan MV, et al. Metformin improves tendon degeneration by blocking translocation of HMGB1 and suppressing tendon inflammation and senescence in aging mice. J Orthop Res, 2023, 41(6): 1162-1176.
46.	Lee SY, Moon SJ, Kim EK, et al. Metformin suppresses systemic autoimmunity in Roquin^san/san mice through inhibiting B cell differentiation into plasma cells via regulation of AMPK/mTOR/STAT3. J Immunol, 2017, 198(7): 2661-2670.
47.	Vasamsetti SB, Karnewar S, Kanugula AK, et al. Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis. Diabetes, 2015, 64(6): 2028-2041.
48.	Alao JP, Legon L, Dabrowska A, et al. Interplays of AMPK and TOR in autophagy regulation in yeast. Cells, 2023, 12(4): 519.
49.	Lamming DW, Ye L, Katajisto P, et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science, 2012, 335(6076): 1638-1643.
50.	Grigg SE, Sarri GL, Gow PJ, et al. Systematic review with meta-analysis: sirolimus- or everolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma. Aliment Pharmacol Ther, 2019, 49(10): 1260-1273.
51.	Chen J, Zhuang L, Li Y, et al. CD8⁺ iTregs mediate the protective effect of rapamycin against graft versus host disease in a humanized murine model. Transpl Immunol, 2023, 77: 101805.
52.	Cheng SC, Quintin J, Cramer RA, et al. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science, 2014, 345(6204): 1250684.
53.	Sinclair LV, Finlay D, Feijoo C, et al. Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking. Nat Immunol, 2008, 9(5): 513-521.
54.	Wang H, Li J, Han Q, et al. IL-12 influence mTOR to modulate CD8⁺ T cells differentiation through T-bet and eomesodermin in response to invasive pulmonary aspergillosis. Int J Med Sci, 2017, 14(10): 977-983.
55.	Farrer LA, Cupples LA, van Duijn CM, et al. Apolipoprotein E genotype in patients with Alzheimer’s disease: implications for the risk of dementia among relatives. Ann Neurol, 1995, 38(5): 797-808.
56.	Shi LZ, Wang R, Huang G, et al. HIF1α-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med, 2011, 208(7): 1367-1376.

1. Roe K. An inflammation classification system using cytokine parameters. Scand J Immunol, 2021, 93(2): e12970. doi: 10.1111/sji.12970.
2. Hillion S, Arleevskaya MI, Blanco P, et al. The innate part of the adaptive immune system. Clin Rev Allergy Immunol, 2020, 58(2): 151-154.
3. Procaccini C, de Candia P, Russo C, et al. Caloric restriction for the immunometabolic control of human health. Cardiovasc Res, 2023, cvad035. doi: 10.1093/cvr/cvad035.
4. Aminzadeh-Gohari S, Kofler B, Herzog C. Dietary restriction in senolysis and prevention and treatment of disease. Crit Rev Food Sci Nutr, 2022, 1-27. doi: 10.1080/10408398.2022.2153355.
5. Zhai J, Kongsberg WH, Pan Y, et al. Caloric restriction induced epigenetic effects on aging. Front Cell Dev Biol, 2023, 10: 1079920.
6. Geltink RIK, Kyle RL, Pearce EL. Unraveling the complex interplay between T cell metabolism and function. Annu Rev Immunol, 2018, 36: 461-488.
7. Matarese G, Sanna V, Fontana S, et al. Leptin as a novel therapeutic target for immune intervention. Curr Drug Targets Inflamm Allergy, 2002, 1(1): 13-22.
8. Van den Bossche J, O’Neill LA, Menon D. Macrophage immunometabolism: where are we (going)?. Trends Immunol, 2017, 38(6): 395-406.
9. Tzelepis F, Blagih J, Khan N, et al. Mitochondrial cyclophilin D regulates T cell metabolic responses and disease tolerance to tuberculosis. Sci Immunol, 2018, 3(23): eaar4135.
10. Koeken VACM, van Crevel R, Netea MG. T cell metabolism has evolved to tolerate tuberculosis. Cell Metab, 2018, 28(3): 332-333.
11. Mercken EM, Crosby SD, Lamming DW, et al. Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile. Aging Cell, 2013, 12(4): 645-651.
12. Redman LM, Smith SR, Burton JH, et al. Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging. Cell Metab, 2018, 27(4): 805-815.
13. Kurki E, Shi J, Martonen E, et al. Distinct effects of calorie restriction on adipose tissue cytokine and angiogenesis profiles in obese and lean mice. Nutr Metab (Lond), 2012, 9(1): 64.
14. Razali N, Hohjoh H, Inazumi T, et al. Induced prostanoid synthesis regulates the balance between Th1- and Th2-producing inflammatory cytokines in the thymus of diet-restricted mice. Biol Pharm Bull, 2020, 43(4): 649-662.
15. Jordan S, Tung N, Casanova-Acebes M, et al. Dietary intake regulates the circulating inflammatory monocyte pool. Cell, 2019, 178(5): 1102-1114.
16. Contreras NA, Fontana L, Tosti V, et al. Calorie restriction induces reversible lymphopenia and lymphoid organ atrophy due to cell redistribution. Geroscience, 2018, 40(3): 279-291.
17. Collins N. Dietary regulation of memory T cells. Int J Mol Sci, 2020, 21(12): 4363.
18. Zhang J, Zhan Z, Li X, et al. Intermittent fasting protects against Alzheimer’s disease possible through restoring aquaporin-4 polarity. Front Mol Neurosci, 2017, 10: 395.
19. Bock M, Steffen F, Zipp F, et al. Impact of dietary intervention on serum neurofilament light chain in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm, 2021, 9(1): e1102. doi: 10.1212/NXI.0000000000001102.
20. Rubovitch V, Pharayra A, Har-Even M, et al. Dietary energy restriction ameliorates cognitive impairment in a mouse model of traumatic brain injury. J Mol Neurosci, 2019, 67(4): 613-621.
21. Roth GS, Ingram DK. Manipulation of health span and function by dietary caloric restriction mimetics. Ann N Y Acad Sci, 2016, 1363: 5-10.
22. Pérez-Ortín JE, Mena A, Barba-Aliaga M, et al. Cell volume homeostatically controls the rDNA repeat copy number and rRNA synthesis rate in yeast. PLoS Genet, 2021, 17(4): e1009520.
23. Cohen HY, Miller C, Bitterman KJ, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science, 2004, 305(5682): 390-392.
24. Lee HJ, Hong YS, Jun W, et al. Nicotinamide riboside ameliorates hepatic metaflammation by modulating NLRP3 inflammasome in a rodent model of type 2 diabetes. J Med Food, 2015, 18(11): 1207-1213.
25. Gariani K, Menzies KJ, Ryu D, et al. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice. Hepatology, 2016, 63(4): 1190-1204.
26. Roboon J, Hattori T, Ishii H, et al. Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide-induced microglial and astrocytic neuroinflammation by increasing NAD. J Neurochem, 2021, 158(2): 311-327.
27. Wang X, Hu X, Yang Y, et al. Nicotinamide mononucleotide protects against β-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Res, 2016, 1643: 1-9.
28. Guo X, Tan S, Wang T, et al. NAD⁺ salvage governs mitochondrial metabolism, invigorating natural killer cell antitumor immunity. Hepatology, 2022 Jul 11. doi: 10.1002/hep.32658.
29. Wei CC, Kong YY, Li GQ, et al. Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway. Sci Rep, 2017, 7(1): 717.
30. Abolaji AO, Adedara AO, Adie MA, et al. Resveratrol prolongs lifespan and improves 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced oxidative damage and behavioural deficits in Drosophila melanogaster. Biochem Biophys Res Commun, 2018, 503(2): 1042-1048.
31. Niu W, Wang H, Wang B, et al. Resveratrol improves muscle regeneration in obese mice through enhancing mitochondrial biogenesis. J Nutr Biochem, 2021, 98: 108804.
32. Nwachukwu JC, Srinivasan S, Bruno NE, et al. Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network. Elife, 2014, 3: e02057.
33. Park SJ, Ahmad F, Philp A, et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell, 2012, 148(3): 421-433.
34. Park SY, Lee SW, Kim HY, et al. SIRT1 inhibits differentiation of monocytes to macrophages: amelioration of synovial inflammation in rheumatoid arthritis. J Mol Med (Berl), 2016, 94(8): 921-931.
35. Totonchi H, Mokarram P, Karima S, et al. Resveratrol promotes liver cell survival in mice liver-induced ischemia-reperfusion through unfolded protein response: a possible approach in liver transplantation. BMC Pharmacol Toxicol, 2022, 23(1): 74.
36. de Queiroz KB, Dos Santos Fontes Pereira T, Araújo MSS, et al. Resveratrol acts anti-inflammatory and neuroprotective in an infant rat model of pneumococcal meningitis by modulating the Hippocampal miRNome. Mol Neurobiol, 2018, 55(12): 8869-8884.
37. Yu D, Zhao XY, Meng QP, et al. Resveratrol activates the SIRT1/PGC-1 pathway in mice to improve synaptic-related cognitive impairment after TBI. Brain Res, 2022, 1796: 148109.
38. Chu H, Li H, Guan X, et al. Resveratrol protects late endothelial progenitor cells from TNF-α-induced inflammatory damage by upregulating Krüppel-like factor-2. Mol Med Rep, 2018, 17(4): 5708-5715.
39. Triggle CR, Mohammed I, Bshesh K, et al. Metformin: is it a drug for all reasons and diseases?. Metabolism, 2022, 133: 155223.
40. LaMoia TE, Shulman GI. Cellular and molecular mechanisms of metformin action. Endocr Rev, 2021, 42(1): 77-96.
41. Zhang J, Huang L, Shi X, et al. Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK/NLRP3 inflammasome pathway. Aging (Albany NY), 2020, 12(23): 24270-24287.
42. Xian H, Liu Y, Rundberg Nilsson A, et al. Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation. Immunity, 2021, 54(7): 1463-1477.
43. Zhao Y, Zhao Y, Tian Y, et al. Metformin suppresses foam cell formation, inflammation and ferroptosis via the AMPK/ERK signaling pathway in ox-LDL-induced THP-1 monocytes. Exp Ther Med, 2022, 24(4): 636.
44. Cheng D, Xu Q, Wang Y, et al. Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling. J Transl Med, 2021, 19(1): 349.
45. Zhang J, Brown R, Hogan MV, et al. Metformin improves tendon degeneration by blocking translocation of HMGB1 and suppressing tendon inflammation and senescence in aging mice. J Orthop Res, 2023, 41(6): 1162-1176.
46. Lee SY, Moon SJ, Kim EK, et al. Metformin suppresses systemic autoimmunity in Roquin^san/san mice through inhibiting B cell differentiation into plasma cells via regulation of AMPK/mTOR/STAT3. J Immunol, 2017, 198(7): 2661-2670.
47. Vasamsetti SB, Karnewar S, Kanugula AK, et al. Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis. Diabetes, 2015, 64(6): 2028-2041.
48. Alao JP, Legon L, Dabrowska A, et al. Interplays of AMPK and TOR in autophagy regulation in yeast. Cells, 2023, 12(4): 519.
49. Lamming DW, Ye L, Katajisto P, et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science, 2012, 335(6076): 1638-1643.
50. Grigg SE, Sarri GL, Gow PJ, et al. Systematic review with meta-analysis: sirolimus- or everolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma. Aliment Pharmacol Ther, 2019, 49(10): 1260-1273.
51. Chen J, Zhuang L, Li Y, et al. CD8⁺ iTregs mediate the protective effect of rapamycin against graft versus host disease in a humanized murine model. Transpl Immunol, 2023, 77: 101805.
52. Cheng SC, Quintin J, Cramer RA, et al. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science, 2014, 345(6204): 1250684.
53. Sinclair LV, Finlay D, Feijoo C, et al. Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking. Nat Immunol, 2008, 9(5): 513-521.
54. Wang H, Li J, Han Q, et al. IL-12 influence mTOR to modulate CD8⁺ T cells differentiation through T-bet and eomesodermin in response to invasive pulmonary aspergillosis. Int J Med Sci, 2017, 14(10): 977-983.
55. Farrer LA, Cupples LA, van Duijn CM, et al. Apolipoprotein E genotype in patients with Alzheimer’s disease: implications for the risk of dementia among relatives. Ann Neurol, 1995, 38(5): 797-808.
56. Shi LZ, Wang R, Huang G, et al. HIF1α-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med, 2011, 208(7): 1367-1376.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Anti-inflammatory effects of caloric restriction and caloric restriction mimetics

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