Metabolic reprogramming in cancer and senescence

Abstract

The rising trend in global cancer incidence has caused widespread concern, one of the main reasons being the aging of the global population. Statistical data show that cancer incidence and mortality rates show a clear upward trend with age. Although there is a commonality between dysregulated nutrient sensing, which is one of the main features of aging, and metabolic reprogramming of tumor cells, the specific regulatory relationship is not clear. This manuscript intends to comprehensively analyze the relationship between senescence and tumor metabolic reprogramming; as well as reveal the impact of key factors leading to cellular senescence on tumorigenesis. In addition, this review summarizes the current intervention strategies targeting nutrient sensing pathways, as well as the clinical cases of treating tumors targeting the characteristics of senescence with the existing nanodelivery research strategies. Finally, it also suggests sensible dietary habits for those who wish to combat aging. In conclusion, this review attempts to sort out the link between aging and metabolism and provide new ideas for cancer treatment.

Keywords

aging / metabolic reprogramming / mitochondrial dysfunction / signaling pathways / tumor

References

[1] López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G, Hallmarks of aging: an expanding universe. Cell. 2023; 186(2): 243-278.

[2] Dodig S, Čepelak I, Pavić I. Hallmarks of senescence and aging. Biochemia medica. 2019; 29(3): 483-497.

[3] Karuturi MS, Sedrak MS, Magnuson A, et al. Breast cancer and aging: standing on the shoulders of a giant. Journal of Geriatric Oncology. 2020; 11(2): 212-216.

[4] Freeland J, Crowell PD, Giafaglione JM, Boutros PC, Goldstein AS. Aging of the progenitor cells that initiate prostate cancer. Cancer Lett. 2021; 515: 28-35.

[5] Greenwell JC, Torres-Gonzalez E, Ritzenthaler JD, Roman J. Interplay between aging, lung inflammation/remodeling, and fibronectin EDA in lung cancer progression. Cancer Biol Ther. 2020; 21(12): 1109-1118.

[6] Macias RI, Monte MJ, Serrano MA, et al. Impact of aging on primary liver cancer: epidemiology, pathogenesis and therapeutics. Aging (Albany NY). 2021; 13(19): 23416.

[7] Avis NE, Deimling GT. Cancer survivorship and aging. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2008; 113(S12): 3519-3529.

[8] Sedrak MS, Kirkland JL, Tchkonia T, Kuchel GA. Accelerated aging in older cancer survivors. J Am Geriatr Soc. 2021; 69(11): 3077.

[9] Ness KK, Wogksch MD. Frailty and aging in cancer survivors. Translational Research. 2020; 221: 65-82.

[10] Yuan L, Alexander PB, Wang X-F. Cellular senescence: from anti-cancer weapon to anti-aging target. Science China Life Sciences. 2020; 63(3): 332-342.

[11] Podhorecka M, Ibanez B, Dmoszyńska A. Metformin–its potential anti-cancer and anti-aging effects. Advances in Hygiene and Experimental Medicine. 2017; 71: 170-175.

[12] Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022; 12(1): 31-46.

[13] Kang H, Kim B, Park J, Youn H, Youn B. The Warburg effect on radioresistance: survival beyond growth. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2023:188988.

[14] Vaupel P, Multhoff G. Revisiting the Warburg effect: historical dogma versus current understanding. J Physiol. 2021; 599(6): 1745-1757.

[15] Pascale RM, Calvisi DF, Simile MM, Feo CF, Feo F. The Warburg effect 97 years after its discovery. Cancers. 2020; 12(10): 2819.

[16] Li Q, Zhang D, Sui X, et al. The Warburg effect drives cachectic states in patients with pancreatobiliary adenocarcinoma. FASEB J. 2023; 37(9): e23144.

[17] Fu Y, Liu S, Yin S, et al. The reverse Warburg effect is likely to be an Achilles’ heel of cancer that can be exploited for cancer therapy. Oncotarget. 2017; 8(34): 57813.

[18] Jaworska M, Szczudło J, Pietrzyk A, et al. The Warburg effect: a score for many instruments in the concert of cancer and cancer niche cells. Pharmacological Reports. 2023; 75(4): 876-890.

[19] Pinto MM, Paumard P, Bouchez C, et al. The Warburg effect and mitochondrial oxidative phosphorylation: friends or foes? Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2023; 1864(1): 148931.

[20] Lu J, Tan M, Cai Q. The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an anti-metastasis mechanism. Cancer Lett. 2015; 356(2): 156-164.

[21] Vaupel P, Schmidberger H, Mayer A. The Warburg effect: essential part of metabolic reprogramming and central contributor to cancer progression. Int J Radiat Biol. 2019; 95(7): 912-919.

[22] Jing Z, Liu Q, He X, et al. NCAPD3 enhances Warburg effect through c-myc and E2F1 and promotes the occurrence and progression of colorectal cancer. J Exp Clin Cancer Res. 2022; 41(1): 198.

[23] Zhang Z, Chen F, Li S, et al. ERG the modulates Warburg effect and tumor progression in cervical cancer. Biochem Biophys Res Commun. 2020; 522(1): 191-197.

[24] Zheng J, Yan X, Lu T, et al. CircFOXK2 promotes hepatocellular carcinoma progression and leads to a poor clinical prognosis via regulating the Warburg effect. J Exp Clin Cancer Res. 2023; 42(1): 63.

[25] Zhong J-T, Zhou S-H. Warburg effect, hexokinase-II, and radioresistance of laryngeal carcinoma. Oncotarget. 2017; 8(8): 14133.

[26] Kim S-H, Baek K-H. Regulation of cancer metabolism by deubiquitinating enzymes: the Warburg effect. Int J Mol Sci. 2021; 22(12): 6173.

[27] Fu X-z, Wang Y. Interferon-γ regulates immunosuppression in septic mice by promoting the Warburg effect through the PI3K/AKT/mTOR pathway. Mol Med. 2023; 29(1): 95.

[28] López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013; 153(6): 1194-1217.

[29] Fernandez del Rio L, Gutiérrez-Casado E, Varela-López A, Villalba JM. Olive oil and the hallmarks of aging. Molecules. 2016; 21(2): 163.

[30] Luo F, Li Y, Yuan F, Zuo J. Hexokinase II promotes the Warburg effect by phosphorylating alpha subunit of pyruvate dehydrogenase. Chinese Journal of Cancer Research. 2019; 31(3): 521.

[31] Chen X-H, Yu D-L, Zhong J-T, Zhou S-H, Fan J, Lu Z-J. Targeted inhibition of HK-II reversed the warburg effect to improve the radiosensitivity of laryngeal carcinoma. Cancer Management and Research. 2021: 8063-8076.

[32] Kane AE, Sinclair DA. Epigenetic changes during aging and their reprogramming potential. Crit Rev Biochem Mol Biol. 2019; 54(1): 61-83.

[33] Li A, Koch Z, Ideker T. Epigenetic aging: biological age prediction and informing a mechanistic theory of aging. J Intern Med. 2022; 292(5): 733-744.

[34] Koemel NA, Skilton MR. Epigenetic aging in early life: role of maternal and early childhood nutrition. Current Nutrition Reports. 2022; 11(2): 318-328.

[35] Bottazzi B, Riboli E, Mantovani A. Aging, inflammation and cancer. Elsevier; 2018: 74-82.

[36] Libby P, Kobold S. Inflammation: a common contributor to cancer, aging, and cardiovascular diseases—expanding the concept of cardio-oncology. Cardiovasc Res. 2019; 115(5): 824-829.

[37] Gulen MF, Samson N, Keller A, et al. cGAS–STING drives ageing-related inflammation and neurodegeneration. Nature. 2023; 620(7973): 374-380.

[38] Loftus M, Hassouneh SA-D, Yooseph S. Bacterial community structure alterations within the colorectal cancer gut microbiome. BMC Microbiol. 2021; 21: 1-18.

[39] Kim HS, Park S-Y, Moon SH, Lee JD, Kim S. Autophagy in human skin fibroblasts: impact of age. Int J Mol Sci. 2018; 19(8): 2254.

[40] Park JW, Kim Y, Lee Sb, et al. Autophagy inhibits cancer stemness in triple-negative breast cancer via miR-181a-mediated regulation of ATG5 and/or ATG2B. Molecular Oncology. 2022; 16(9): 1857-1875.

[41] Xu F, Zhang C, Zou Z, et al. Aging-related Atg5 defect impairs neutrophil extracellular traps formation. Immunology. 2017; 151(4): 417-432.

[42] Liu Y, Baba Y, Ishimoto T, et al. Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma. Br J Cancer. 2021; 124(5): 963-974.

[43] Gui Z, Zhao Z, Sun Q, et al. LncRNA FEZF1-AS1 promotes multi-drug resistance of gastric cancer cells via upregulating ATG5. Front Cell Dev Biol. 2021; 9: 749129.

[44] Maheshwari C, Vidoni C, Titone R, et al. Isolation, characterization, and autophagy function of BECN1-splicing isoforms in cancer cells. Biomolecules. 2022; 12(8): 1069.

[45] Sebti S, Zou Z, Shiloh MU. BECN1F121A mutation increases autophagic flux in aged mice and improves aging phenotypes in an organ-dependent manner. Autophagy. 2023; 19(3): 957-965.

[46] Warburg O. The metabolism of carcinoma cells. The Journal of Cancer Research. 1925; 9(1): 148-163.

[47] Schwartz L, T Supuran C, O Alfarouk K. The Warburg effect and the hallmarks of cancer. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2017; 17(2): 164-170.

[48] Gonzalez PS, O’Prey J, Cardaci S, et al. Mannose impairs tumour growth and enhances chemotherapy. Nature. 2018; 563(7733): 719-723.

[49] Lu J. The Warburg metabolism fuels tumor metastasis. Cancer Metastasis Rev. 2019; 38: 157-164.

[50] Liao M, Yao D, Wu L, et al. Targeting the Warburg effect: a revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer. Acta Pharmaceutica Sinica B. 2023;

[51] Fukushi A, Kim H-D, Chang Y-C, Kim C-H. Revisited metabolic control and reprogramming cancers by means of the warburg effect in tumor cells. Int J Mol Sci. 2022; 23(17): 10037.

[52] Chen L, Huang L, Gu Y, Cang W, Sun P, Xiang Y. Lactate-lactylation hands between metabolic reprogramming and immunosuppression. Int J Mol Sci. 2022; 23(19): 11943.

[53] Zha J, Zhang J, Lu J, et al. A review of lactate-lactylation in malignancy: its potential in immunotherapy. Front Immunol. 2024; 15: 1384948.

[54] Kierans S, Taylor C. Regulation of glycolysis by the hypoxia-inducible factor (HIF): implications for cellular physiology. J Physiol. 2021; 599(1): 23-37.

[55] Pan T, Sun S, Chen Y, et al. Immune effects of PI3K/Akt/HIF-1α-regulated glycolysis in polymorphonuclear neutrophils during sepsis. Critical Care. 2022; 26(1): 29.

[56] Lu H, Lin J, Xu C, et al. Cyclosporine modulates neutrophil functions via the SIRT6–HIF-1α–glycolysis axis to alleviate severe ulcerative colitis. Clin Transl Med. 2021; 11(2): e334.

[57] Rashid M, Zadeh LR, Baradaran B, et al. Up-down regulation of HIF-1α in cancer progression. Gene. 2021; 798: 145796.

[58] Harris RA, Tindale L, Cumming RC. Age-dependent metabolic dysregulation in cancer and Alzheimer’s disease. Biogerontology. 2014; 15: 559-577.

[59] Peng F, Wang J, Fan W, et al. Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia. Oncogene. 2018; 37(8): 1062-1074.

[60] Pi M, Kuang H, Yue C, et al. Targeting metabolism to overcome cancer drug resistance: a promising therapeutic strategy for diffuse large B cell lymphoma. Drug Resist Updat. 2022; 61: 100822.

[61] Guo N, Ma H, Li D, Fan H, Sun C, Sun Y. CS-NO suppresses inhibits glycolysis and gastric cancer progression through regulating YAP/TAZ signaling pathway. Cell Biochem Biophys. 2023; 81(3): 561-567.

[62] Enzo E, Santinon G, Pocaterra A, et al. Aerobic glycolysis tunes YAP/TAZ transcriptional activity. EMBO J. 2015; 34(10): 1349-1370.

[63] Hsieh AL, Walton ZE, Altman BJ, Stine ZE, Dang CV. MYC and Metabolism on the Path to Cancer. Elsevier; 2015: 11-21.

[64] Lin J, Wang X, Zhai S, et al. Hypoxia-induced exosomal circPDK1 promotes pancreatic cancer glycolysis via c-myc activation by modulating miR-628-3p/BPTF axis and degrading BIN1. J Hematol Oncol. 2022; 15(1): 128.

[65] Hsu C-C, Peng D, Cai Z, Lin H-K. AMPK Signaling and its Targeting in Cancer Progression and Treatment. Elsevier; 2022: 52-68.

[66] Lü S, Zhao H, Parsons EP, et al. The glossyhead1 allele of ACC1 reveals a principal role for multidomain acetyl-coenzyme A carboxylase in the biosynthesis of cuticular waxes by Arabidopsis. Plant Physiol. 2011; 157(3): 1079-1092.

[67] Ruderman NB, Saha AK. Metabolic syndrome: adenosine monophosphate-activated protein kinase and malonyl coenzyme A. Obesity. 2006; 14(S2): 25S-33S.

[68] Mukhopadhyay S, Vander Heiden MG, McCormick F. The metabolic landscape of RAS-driven cancers from biology to therapy. Nature cancer. 2021; 2(3): 271-283.

[69] Lavoie H, Therrien M. Structural Keys Unlock RAS–MAPK Cellular Signalling Pathway. Nature Publishing Group UK London; 2022.

[70] Li Q, Li Z, Luo T, Shi H. Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy. Mol Biomedi. 2022; 3(1): 47.

[71] Mondal P, Gadad SS, Adhikari S, et al. TCF19 and p53 regulate transcription of TIGAR and SCO2 in HCC for mitochondrial energy metabolism and stress adaptation. FASEB J. 2021; 35(9): e21814.

[72] Qi Z, He J, Su Y, et al. Physical exercise regulates p53 activity targeting SCO2 and increases mitochondrial COX biogenesis in cardiac muscle with age. PLoS One. 2011; 6(7): e21140.

[73] Won KY, Lim S-J, Kim GY, et al. Regulatory role of p53 in cancer metabolism via SCO2 and TIGAR in human breast cancer. Hum Pathol. 2012; 43(2): 221-228.

[74] Guo Y, Chi X, Wang Y, et al. Mitochondria transfer enhances proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cell and promotes bone defect healing. Stem Cell Research & Therapy. 2020; 11: 1-16.

[75] Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of cellular senescence. Trends Cell Biol. 2018; 28(6): 436-453.

[76] Timofeev O, Koch L, Niederau C, et al. Phosphorylation control of p53 DNA-binding cooperativity balances tumorigenesis and aging. Cancer Res. 2020; 80(23): 5231-5244.

[77] Chibaya L, Karim B, Zhang H, Jones SN. Mdm2 phosphorylation by Akt regulates the p53 response to oxidative stress to promote cell proliferation and tumorigenesis. Proc Natl Acad Sci USA. 2021; 118(4): e2003193118.

[78] Amirthalingam M, Palanisamy S, Tawata S. p21-Activated kinase 1 (PAK1) in aging and longevity: an overview. Ageing Res Rev. 2021; 71: 101443.

[79] Shao J-H, Fu Q-W, Li L-X, et al. Prx II reduces oxidative stress and cell senescence in chondrocytes by activating the p16-CDK4/6-pRb-E2F signaling pathway. European Review for Medical & Pharmacological Sciences. 2020; 24(7): 3448-3458

[80] Matias I, Diniz LP, Damico IV, et al. Loss of lamin-B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus. Aging Cell. 2022; 21(1): e13521.

[81] Gao S, Chen L, Lin Z, et al. 8-Oxoguanine DNA glycosylase protects cells from senescence via the p53-p21 pathway: oGG1 inhibits cell senescence through p53-p21 pathway. Acta Biochim Biophy Sin. 2024; 56(2): 184.

[82] Kirkland JL, Tchkonia T. Cellular senescence: a translational perspective. EBioMedicine. 2017; 21: 21-28.

[83] Fischer M, Schade AE, Branigan TB, Müller GA, DeCaprio JA. Coordinating gene expression during the cell cycle. Trends Biochem Sci. 2022; 47(12): 1009-1022.

[84] Walker AE, Morgan RG, Ives SJ, et al. Age-related arterial telomere uncapping and senescence is greater in women compared with men. Acta Physiologica (Oxford, England). 2012; 206(2): 135.

[85] Gioia U, Tavella S, Martínez-Orellana P, et al. SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence. Nat Cell Biol. 2023; 25(4): 550-564.

[86] Doolittle ML, Saul D, Kaur J, et al. Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton. Nat Commun. 2023; 14(1): 4587.

[87] Yu C, Xiao J-H. The Keap1-Nrf2 system: a mediator between oxidative stress and aging. Oxid Med Cell Long. 2021; 2021(1): 6635460.

[88] Hajam YA, Rani R, Ganie SY, et al. Oxidative stress in human pathology and aging: molecular mechanisms and perspectives. Cells. 2022; 11(3): 552.

[89] Koutsaliaris IK, Moschonas IC, Pechlivani LM, Tsouka AN, Tselepis AD. Inflammation, oxidative stress, vascular aging and atherosclerotic ischemic stroke. Curr Med Chem. 2022; 29(34): 5496-5509.

[90] Anwar S, Shamsi A, Mohammad T, Islam A, Hassan MI. Targeting pyruvate dehydrogenase kinase signaling in the development of effective cancer therapy. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2021; 1876(1): 188568.

[91] Hagen TM, Yowe DL, Bartholomew JC, et al. Mitochondrial decay in hepatocytes from old rats: membrane potential declines, heterogeneity and oxidants increase. Proc Natl Acad Sci USA. 1997; 94(7): 3064-3069.

[92] Gallo G, Rubattu S, Volpe M. Mitochondrial dysfunction in heart failure: from pathophysiological mechanisms to therapeutic opportunities. Int J Mol Sci. 2024; 25(5): 2667.

[93] Li M, Xu B, Li X, et al. Mitofusin 2 confers the suppression of microglial activation by cannabidiol: insights from in vitro and in vivo models. Brain Behav Immun. 2022; 104: 155-170.

[94] Correia-Melo C, Marques F, Anderson R, et al. Mitochondria are required for pro-ageing features of the senescent phenotype. EMBO J. 2016; 35: 724-742.

[95] Flores A, Sandoval-Gonzalez S, Takahashi R, et al. Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin. Nat Commun. 2019; 10(1): 91.

[96] Flores A, Schell J, Krall AS, et al. Lactate dehydrogenase activity drives hair follicle stem cell activation. Nat Cell Biol. 2017; 19(9): 1017-1026.

[97] Boyarski A, Shlush N, Paz S, Eichler J, Alfonta L. Electrochemical characterization of a dual cytochrome-containing lactate dehydrogenase. Bioelectrochemistry. 2023; 152: 108406.

[98] Christov PP, Kim K, Jana S, et al. Optimization of ether and aniline based inhibitors of lactate dehydrogenase. Bioorg Med Chem Lett. 2021; 41: 127974.

[99] Liu B, Wang C, Weng Z, et al. Glycolytic enzyme PKM2 regulates cell senescence but not inflammation in the process of osteoarthritis: pKM2 regulates chondrocyte senescence via p16 INK4a transcription. Acta Biochim Biophy Sin. 2023; 55(9): 1425.

[100] Wu Y, Tang L, Huang H, et al. Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence. Nat Commun. 2023; 14(1): 1323.

[101] Shimada N, Shinagawa T, Ishii S. Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein. Genes Cells. 2008; 13(3): 245-254.

[102] Xu Q, Fu Q, Li Z, et al. The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice. Nature Metabolism. 2021; 3(12): 1706-1726.

[103] Prasanna PG, Citrin DE, Hildesheim J, et al. Therapy-induced senescence: opportunities to improve anticancer therapy. J Natl Cancer Inst. 2021; 113(10): 1285-1298.

[104] Beard E, Lengacher S, Dias S, Magistretti PJ, Finsterwald C. Astrocytes as key regulators of brain energy metabolism: new therapeutic perspectives. Frontiers in physiology. 2022; 12: 825816.

[105] Wang Z, Wei D, Bin E, et al. Enhanced glycolysis-mediated energy production in alveolar stem cells is required for alveolar regeneration. Cell Stem Cell. 2023; 30(8): 1028-1042. e7.

[106] Shahmirzadi AA, Edgar D, Liao C-Y, et al. Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice. Cell Metab. 2020; 32(3): 447-456. e6.

[107] Calcinotto A, Kohli J, Zagato E, Pellegrini L, Demaria M, Alimonti A. Cellular senescence: aging, cancer, and injury. Physiol Rev. 2019; 99(2): 1047-1078.

[108] Mylonas KJ, O’Sullivan ED, Humphries D, et al. Cellular senescence inhibits renal regeneration after injury in mice, with senolytic treatment promoting repair. Sci Transl Med. 2021; 13(594): eabb0203.

[109] Duan JL, Ruan B, Song P, et al. Shear stress–induced cellular senescence blunts liver regeneration through Notch–sirtuin 1–P21/P16 axis. Hepatology. 2022; 75(3): 584-599.

[110] Martínez-Gayo A, Félix-Soriano E, Sáinz N, González-Muniesa P, Moreno-Aliaga MJ. Changes induced by aging and long-term exercise and/or DHA supplementation in muscle of obese female mice. Nutrients. 2022; 14(20): 4240.

[111] Zhang G, Dong R, Kong D, Liu B, Zha Y, Luo M. The effect of GLUT1 on the survival rate and immune cell infiltration of lung adenocarcinoma and squamous cell carcinoma: a meta and bioinformatics analysis. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2022; 22(2): 223-238.

[112] Li CJ, Lin LT, Tsai HW, Wen ZH, Tsui KH. Phosphoglycerate mutase family member 5 maintains oocyte quality via mitochondrial dynamic rearrangement during aging. Aging Cell. 2022; 21(2): e13546.

[113] Hiremath LS, Rothstein M. The effect of aging on rat liver phosphoglycerate kinase and comparison with the muscle enzyme. Biochimica et Biophysica Acta (BBA)-Protein Structure and Molecular Enzymology. 1982; 705(2): 200-209.

[114] Martinez-Outschoorn UE, Lin Z, Ko Y-H, et al. Understanding the metabolic basis of drug resistance: therapeutic induction of the Warburg effect kills cancer cells. Cell Cycle. 2011; 10(15): 2521-2528.

[115] Zhou W, Yang X, Wang H, Yao W, Chu D, Wu F. Neuronal aerobic glycolysis exacerbates synapse loss in aging mice. Exp Neurol. 2024; 371: 114590.

[116] Zorec R, Vardjan N. Adrenergic regulation of astroglial aerobic glycolysis and lipid metabolism: towards a noradrenergic hypothesis of neurodegeneration. Neurobiol Dis. 2023; 182: 106132.

[117] Jomova K, Raptova R, Alomar SY, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol. 2023; 97(10): 2499-2574.

[118] Yang S, Li A, Lv L, et al. Exosomal miRNA-146a-5p derived from senescent hepatocellular carcinoma cells promotes aging and inhibits aerobic glycolysis in liver cells via targeting IRF7. J Cancer. 2024; 15(14): 4448.

[119] Dou X, Fu Q, Long Q, et al. PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy. Nature Metabolism. 2023; 5(11): 1887-1910.

[120] Lee H, Jeon JH, Lee Y-J, et al. Inhibition of pyruvate dehydrogenase kinase 4 in CD4+ T cells ameliorates intestinal inflammation. Cellular and Molecular Gastroenterology and Hepatology. 2023; 15(2): 439-461.

[121] Medes G, Thomas A, Weinhouse S. Metabolism of neoplastic tissue. IV. A study of lipid synthesis in neoplastic tissue slices in vitro. Cancer Res. 1953; 13(1): 27-29.

[122] Swinnen JV, Heemers H, Van de Sande T, et al. Androgens, lipogenesis and prostate cancer. J Steroid Biochem Mol Biol. 2004; 92(4): 273-279.

[123] Roy D, Mondal S, Wang C, et al. Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer. Cancer & Metabolism. 2014; 2: 1-17.

[124] Ma K, Zhang L. Overview: lipid metabolism in the tumor microenvironment. Adv Exp Med Biol. 2021; 1316: 41-47.

[125] Jin H-R, Wang J, Wang Z-J, et al. Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics. J Hematol Oncol. 2023; 16(1): 103.

[126] Ricoult SJ, Yecies JL, Ben-Sahra I, Manning BD. Oncogenic PI3K and K-Ras stimulate de novo lipid synthesis through mTORC1 and SREBP. Oncogene. 2016; 35(10): 1250-1260.

[127] Khan F, Elsori D, Verma M, et al. Unraveling the intricate relationship between lipid metabolism and oncogenic signaling pathways. Front Cell Dev Biol. 2024; 12: 1399065.

[128] Hamsanathan S, Gurkar AU. Lipids as regulators of cellular senescence. Frontiers in Physiology. 2022; 13: 796850.

[129] Zeng Q, Gong Y, Zhu N, Shi Y, Zhang C, Qin L. Lipids and lipid metabolism in cellular senescence: emerging targets for age-related diseases. Ageing Res Rev. 2024:102294.

[130] Yasuda T, Koiwa M, Yonemura A, et al. Inflammation-driven senescence-associated secretory phenotype in cancer-associated fibroblasts enhances peritoneal dissemination. Cell Rep. 2021; 34(8)

[131] Alicea GM, Rebecca VW, Goldman AR, et al. Changes in aged fibroblast lipid metabolism induce age-dependent melanoma cell resistance to targeted therapy via the fatty acid transporter FATP2. Cancer Discov. 2020; 10(9): 1282-1295.

[132] Liu X, Hartman CL, Li L, et al. Reprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy. Sci Transl Med. 2021; 13(587): eaaz6314.

[133] Mosier JA, Schwager SC, Boyajian DA, Reinhart-King CA. Cancer cell metabolic plasticity in migration and metastasis. Clin Exp Metastasis. 2021; 38(4): 343-359.

[134] Bian X, Liu R, Meng Y, Xing D, Xu D, Lu Z. Lipid metabolism and cancer. J Exp Med. 2021; 218(1): 784

[135] Cha YJ, Kim E-S, Koo JS. Amino acid transporters and glutamine metabolism in breast cancer. Int J Mol Sci. 2018; 19(3): 907.

[136] Maddocks OD, Athineos D, Cheung EC, et al. Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature. 2017; 544(7650): 372-376.

[137] Tombari C, Zannini A, Bertolio R, et al. Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth. Nat Commun. 2023; 14(1): 6777.

[138] Deutz NE, Thaden JJ, Ten Have GA, Walker DK, Engelen MP. Metabolic phenotyping using kinetic measurements in young and older healthy adults. Metabolism. 2018; 78: 167-178.

[139] Paukštytė J, Cabezas RML, Feng Y, et al. Global analysis of aging-related protein structural changes uncovers enzyme-polymerization-based control of longevity. Mol Cell. 2023; 83(18): 3360-3376. e11.

[140] Dai D, Wang J, Zhang H, Wu S, Qi G. Uterine microbial communities and their potential role in the regulation of epithelium cell cycle and apoptosis in aged hens. Microbiome. 2023; 11(1): 251.

[141] Xu Q, Li Y, Gao X, et al. HNF4α regulates sulfur amino acid metabolism and confers sensitivity to methionine restriction in liver cancer. Nat Commun. 2020; 11(1): 3978.

[142] Martin DE, Torrance BL, Haynes L, Bartley JM. Targeting aging: lessons learned from immunometabolism and cellular senescence. Front Immunol. 2021; 12: 714742.

[143] Akha AAS. Aging and the immune system: an overview. J Immunol Methods. 2018; 463: 21-26.

[144] Noorolyai S, Shajari N, Baghbani E, Sadreddini S, Baradaran B. The relation between PI3K/AKT signalling pathway and cancer. Gene. 2019; 698: 120-128.

[145] Wang Y, Luo M, Wang F, et al. AMPK induces degradation of the transcriptional repressor PROX1 impairing branched amino acid metabolism and tumourigenesis. Nat Commun. 2022; 13(1): 7215.

[146] Palmer CS, Anderson AJ, Stojanovski D. Mitochondrial protein import dysfunction: mitochondrial disease, neurodegenerative disease and cancer. FEBS Lett. 2021; 595(8): 1107-1131.

[147] Perrone S, Lotti F, Geronzi U, Guidoni E, Longini M, Buonocore G. Oxidative stress in cancer-prone genetic diseases in pediatric age: the role of mitochondrial dysfunction. Oxid Med Cell Long. 2016; 2016(1): 4782426.

[148] Ma Z, Han H, Zhao Y. Mitochondrial dysfunction-targeted nanosystems for precise tumor therapeutics. Biomaterials. 2023; 293: 121947.

[149] Vujic A, Koo AN, Prag HA, Krieg T. Mitochondrial redox and TCA cycle metabolite signaling in the heart. Free Radical Biol Med. 2021; 166: 287-296.

[150] Bhatti JS, Bhatti GK, Reddy PH. Mitochondrial dysfunction and oxidative stress in metabolic disorders—A step towards mitochondria based therapeutic strategies. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2017; 1863(5): 1066-1077.

[151] Pinto M, Moraes CT. Mechanisms linking mtDNA damage and aging. Free Radical Biol Med. 2015; 85: 250-258.

[152] Treem WR, Sokol RJ. Disorders of the Mitochondria. © 1998 by Thieme Medical Publishers, Inc.; 1998: 237-253.

[153] Du X, Zhang Y, Wu H, et al. ROS-mediated TCA cycle is greatly related to the UV resistance of Bacillus thuringiensis. Pestic Biochem Physiol. 2023; 193: 105429.

[154] Liu Y, Liu K, Thorne RF, et al. Mitochondrial SENP2 regulates the assembly of SDH complex under metabolic stress. Cell Rep. 2023; 42(2)

[155] Taïeb D, Wanna GB, Ahmad M, et al. Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants. Lancet Diabetes Endocrinol. 2023; 11(5): 345-361.

[156] Neitzel C, Demuth P, Wittmann S, Fahrer J. Targeting altered energy metabolism in colorectal cancer: oncogenic reprogramming, the central role of the TCA cycle and therapeutic opportunities. Cancers. 2020; 12(7): 1731.

[157] Wilde BR, Chakraborty N, Matulionis N, et al. FH variant pathogenicity promotes purine salvage pathway dependence in kidney cancer. Cancer Discov. 2023; 13(9): 2072-2089.

[158] Kurbacher CM, Cree IA. Chemosensitivity testing using microplate adenosine triphosphate-based luminescence measurements. Methods Mol Med. 2005; 110: 101-120.

[159] Zhang L, Fu W, Zheng L, et al. A clinicopathological and molecular analysis of sellar/suprasellar neurocytoma mimicking pituitary adenoma. Frontiers in Endocrinology. 2022; 13: 861540.

[160] Aspuria P-JP, Lunt SY, Väremo L, et al. Succinate dehydrogenase inhibition leads to epithelial-mesenchymal transition and reprogrammed carbon metabolism. Cancer & metabolism. 2014; 2: 1-15.

[161] Jaakkola P, Mole DR, Tian Y-M, et al. Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001; 292(5516): 468-472.

[162] Chen J-X, Li L, Cantrell AC, Williams QA, Zeng H. High glucose activates prolyl hydroxylases and disrupts HIF-α signaling via the P53/TIGAR pathway in cardiomyocyte. Cells. 2023; 12(7): 1060.

[163] Lawson H, Holt-Martyn JP, Dembitz V, et al. The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia. Nature Cancer. 2024: 1-22.

[164] Jiang B, Zhang J, Zhao G, et al. Filamentous GLS1 promotes ROS-induced apoptosis upon glutamine deprivation via insufficient asparagine synthesis. Mol Cell. 2022; 82(10): 1821-1835. e6.

[165] Noster J, Persicke M, Chao T-C, et al. Impact of ROS-induced damage of TCA cycle enzymes on metabolism and virulence of Salmonella enterica serovar Typhimurium. Front Microbiol. 2019; 10: 762.

[166] Lee SH, Duron HE, Chaudhuri D. Beyond the TCA cycle: new insights into mitochondrial calcium regulation of oxidative phosphorylation. Biochem Soc Trans. 2023; 51(4): 1661-1673.

[167] Cui Q, Wang J-Q, Assaraf YG, et al. Modulating ROS to overcome multidrug resistance in cancer. Drug Resist Updat. 2018; 41: 1-25.

[168] de Sá Junior PL, Câmara DAD, Porcacchia AS, et al. The roles of ROS in cancer heterogeneity and therapy. Oxid Med Cell Long. 2017; 2017(1): 2467940.

[169] Yang Y, Karakhanova S, Hartwig W, et al. Mitochondria and mitochondrial ROS in cancer: novel targets for anticancer therapy. J Cell Physiol. 2016; 231(12): 2570-2581.

[170] Ziech D, Franco R, Pappa A, Panayiotidis MI. Reactive oxygen species (ROS)-induced genetic and epigenetic alterations in human carcinogenesis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2011; 711(1-2): 167-173.

[171] Jadeja RN, Martin PM, Chen W. Mitochondrial oxidative stress and energy metabolism: impact on aging and longevity. Oxid Med Cell Long. 2021; 2021:9789086

[172] Korbecki J, Simińska D, Gąssowska-Dobrowolska M, et al. Chronic and cycling hypoxia: drivers of cancer chronic inflammation through HIF-1 and NF-κB activation: a review of the molecular mechanisms. Int J Mol Sci. 2021; 22(19): 10701.

[173] Kakimoto PA, Kowaltowski AJ. Effects of high fat diets on rodent liver bioenergetics and oxidative imbalance. Redox Biol. 2016; 8: 216-225.

[174] Jassim AH, Fan Y, Pappenhagen N, Nsiah NY, Inman DM. Oxidative stress and hypoxia modify mitochondrial homeostasis during glaucoma. Antioxid Redox Signal. 2021; 35(16): 1341-1357.

[175] Islam Bu, Jabir NR, Tabrez S. The role of mitochondrial defects and oxidative stress in Alzheimer’s disease. J Drug Targeting. 2019; 27(9): 932-942.

[176] Malla RR, Kamal MA. ROS-responsive nanomedicine: towards targeting the breast tumor microenvironment. Curr Med Chem. 2021; 28(28): 5674-5698.

[177] An J, Hu Y-G, Cheng K, et al. ROS-augmented and tumor-microenvironment responsive biodegradable nanoplatform for enhancing chemo-sonodynamic therapy. Biomaterials. 2020; 234: 119761.

[178] Herst PM, Carson GM, Eccles DA, Berridge MV. Bioenergetic and metabolic adaptation in tumor progression and metastasis. Front Oncol. 2022; 12: 857686.

[179] Ren Y, Wang R, Weng S, et al. Multifaceted role of redox pattern in the tumor immune microenvironment regarding autophagy and apoptosis. Mol Cancer. 2023; 22(1): 130.

[180] Yadav N, Chandra D. Mitochondrial DNA mutations and breast tumorigenesis. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2013; 1836(2): 336-344.

[181] Ericson NG, Kulawiec M, Vermulst M, et al. Decreased mitochondrial DNA mutagenesis in human colorectal cancer. PLoS Genet. 2012; 8(6): e1002689.

[182] Luo Y, Ma J, Lu W. The significance of mitochondrial dysfunction in cancer. Int J Mol Sci. 2020; 21(16): 5598.

[183] Baris OR, Klose A, Kloepper JE, et al. The mitochondrial electron transport chain is dispensable for proliferation and differentiation of epidermal progenitor cells. Stem Cells. 2011; 29(9): 1459-1468.

[184] Spinazzola A, Perez-Rodriguez D, Ježek J, Holt IJ. Mitochondrial DNA competition: starving out the mutant genome. Trends Pharmacol Sci. 2024;

[185] Kassauei K, Habbe N, Mullendore ME, Karikari CA, Maitra A, Feldmann G. Mitochondrial DNA mutations in pancreatic cancer. Int J Gastrointest Cancer. 2006; 37: 57-64.

[186] Dunn J, Grider MH. Physiology, adenosine triphosphate. 2020;

[187] Dasgupta S, Hoque MO, Upadhyay S, Sidransky D. Mitochondrial cytochrome B gene mutation promotes tumor growth in bladder cancer. Cancer Res. 2008; 68(3): 700-706.

[188] Zhu Y, Han X-Q, Sun X-J, Yang R, Ma W-Q, Liu N-F. Lactate accelerates vascular calcification through NR4A1-regulated mitochondrial fission and BNIP3-related mitophagy. Apoptosis. 2020; 25: 321-340.

[189] Ogasawara E, Nakada K, Ishihara N. Distal control of mitochondrial biogenesis and respiratory activity by extracellular lactate caused by large-scale deletion of mitochondrial DNA. Pharmacol Res. 2020; 160: 105204.

[190] Guo X-G, Liu C-T, Dai H, Guo Q-N. Mutations in the mitochondrial ATPase6 gene are frequent in human osteosarcoma. Exp Mol Pathol. 2013; 94(1): 285-288.

[191] Grzybowska-Szatkowska L, Ślaska B, Rzymowska J, Brzozowska A, Floriańczyk B. Novel mitochondrial mutations in the ATP6 and ATP8 genes in patients with breast cancer. Molecular Medicine Reports. 2014; 10(4): 1772-1778.

[192] Uchenunu O, Zhdanov AV, Hutton P, et al. Mitochondrial complex IV defects induce metabolic and signaling perturbations that expose potential vulnerabilities in HCT116 cells. FEBS Open bio. 2022; 12(5): 959-982.

[193] Bameri O, Salarzaei M, Parooie F. KRAS/BRAF mutations in brain arteriovenous malformations: a systematic review and meta-analysis. Interventional Neuroradiology. 2021; 27(4): 539-546.

[194] Topham JT, Tsang ES, Karasinska JM, et al. Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma. Nat Commun. 2022; 13(1): 5941.

[195] Hong T, Yan Y, Li J, et al. High prevalence of KRAS/BRAF somatic mutations in brain and spinal cord arteriovenous malformations. Brain. 2019; 142(1): 23-34.

[196] Liou G-Y, Döppler H, DelGiorno KE, et al. Mutant KRas-induced mitochondrial oxidative stress in acinar cells upregulates EGFR signaling to drive formation of pancreatic precancerous lesions. Cell Rep. 2016; 14(10): 2325-2336.

[197] Viale A, Pettazzoni P, Lyssiotis CA, et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 2014; 514(7524): 628-632.

[198] Ren X, Yan J, Zhao Q, et al. The Fe–S cluster assembly protein IscU2 increases α-ketoglutarate catabolism and DNA 5mC to promote tumor growth. Cell Discov. 2023; 9(1): 76.

[199] Yun J, Mullarky E, Lu C, et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science. 2015; 350(6266): 1391-1396.

[200] Ludikhuize MC, Gevers S, Nguyen NT, et al. Rewiring glucose metabolism improves 5-FU efficacy in p53-deficient/KRAS G12D glycolytic colorectal tumors. Commun Biol. 2022; 5(1): 1159.

[201] Chang X, Liu X, Wang H, Yang X, Gu Y. Glycolysis in the progression of pancreatic cancer. American Journal of Cancer Research. 2022; 12(2): 861.

[202] Shin N, Lee HJ, Sim DY, et al. Apoptotic effect of compound K in hepatocellular carcinoma cells via inhibition of glycolysis and Akt/mTOR/c-Myc signaling. Phytother Res. 2021; 35(7): 3812-3820.

[203] Jiang X, Guo S, Wang S, et al. EIF4A3-induced circARHGAP29 promotes aerobic glycolysis in docetaxel-resistant prostate cancer through IGF2BP2/c-Myc/LDHA signaling. Cancer Res. 2022; 82(5): 831-845.

[204] Zhang X, Ai Z, Chen J, et al. Glycometabolic adaptation mediates the insensitivity of drug-resistant K562/ADM leukaemia cells to adriamycin via the AKT-mTOR/c-Myc signalling pathway. Molecular medicine reports. 2017; 15(4): 1869-1876.

[205] Kfoury A, Armaro M, Collodet C, et al. AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress. EMBO J. 2018; 37(5): e97673.

[206] Pandkar MR, Sinha S, Samaiya A, Shukla S. Oncometabolite lactate enhances breast cancer progression by orchestrating histone lactylation-dependent c-Myc expression. Translational Oncology. 2023; 37: 101758.

[207] Clementino M, Xie J, Yang P, et al. A positive feedback loop between c-Myc upregulation, glycolytic shift, and histone acetylation enhances cancer stem cell-like property and tumorigenicity of Cr (VI)-transformed cells. Toxicol Sci. 2020; 177(1): 71-83.

[208] Wiley CD, Velarde MC, Lecot P, et al. Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab. 2016; 23(2): 303-314.

[209] Amorim JA, Coppotelli G, Rolo AP, Palmeira CM, Ross JM, Sinclair DA. Mitochondrial and metabolic dysfunction in ageing and age-related diseases. Nat Rev Endocrinol. 2022; 18(4): 243-258.

[210] Farfariello V, Gordienko DV, Mesilmany L, et al. TRPC3 shapes the ER-mitochondria Ca2+ transfer characterizing tumour-promoting senescence. Nat Commun. 2022; 13(1): 956.

[211] Cipolla CM, Lodhi IJ. Peroxisomal dysfunction in age-related diseases. Trends in Endocrinology & Metabolism. 2017; 28(4): 297-308.

[212] Guda P, Guda C, Subramaniam S. Reconstruction of pathways associated with amino acid metabolism in human mitochondria. Genomics, Proteomics and Bioinformatics. 2007; 5(3-4): 166-176.

[213] Hewton KG, Johal AS, Parker SJ. Transporters at the interface between cytosolic and mitochondrial amino acid metabolism. Metabolites. 2021; 11(2): 112.

[214] Yoo HC, Park SJ, Nam M, et al. A variant of SLC1A5 is a mitochondrial glutamine transporter for metabolic reprogramming in cancer cells. Cell Metab. 2020; 31(2): 267-283. e12.

[215] Liu Y, Wang Y, Lin Z, Kang R, Tang D, Liu J. SLC25A22 as a key mitochondrial transporter against ferroptosis by producing glutathione and monounsaturated fatty acids. Antioxid Redox Signal. 2023; 39(1-3): 166-185.

[216] Kunji ER, King MS, Ruprecht JJ, Thangaratnarajah C. The SLC25 carrier family: important transport proteins in mitochondrial physiology and pathology. Physiology. 2020; 35(5): 302-327.

[217] Lucas V, Cavadas C, Aveleira CA. Cellular senescence: from mechanisms to current biomarkers and senotherapies. Pharmacol Rev. 2023; 75(4): 675-713.

[218] Sagiv A, Krizhanovsky V. Immunosurveillance of senescent cells: the bright side of the senescence program. Biogerontology. 2013; 14: 617-628.

[219] Prata LGL, Ovsyannikova IG, Tchkonia T, Kirkland JL. Senescent cell clearance by the immune system: Emerging therapeutic opportunities. Elsevier; 2018:101275.

[220] Yan J, Ma L-P, Liu F, et al. Effect of ultraviolet B irradiation on melanin content accompanied by the activation of p62/GATA4-mediated premature senescence in HaCaT cells. Dose-Response. 2022; 20(1): 15593258221075321.

[221] Salminen A, Ojala J, Kaarniranta K. Apoptosis and aging: increased resistance to apoptosis enhances the aging process. Cell Mol Life Sci. 2011; 68: 1021-1031.

[222] Laberge R-M, Sun Y, Orjalo AV, et al. MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol. 2015; 17(8): 1049-1061.

[223] 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.

[224] Schmid G, Kramer MP, Maurer M, Wandl S, Węsierska-Gądek J. Cellular and organismal ageing: role of the p53 tumor suppressor protein in the induction of transient and terminal senescence. J Cell Biochem. 2007; 101(6): 1355-1369.

[225] García-Cao I, García-Cao M, Martín-Caballero J, et al. ’Super p53’mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J. 2002;

[226] Zheng JH, Viacava Follis A, Kriwacki RW, Moldoveanu T. Discoveries and controversies in BCL-2 protein-mediated apoptosis. FEBS J. 2016; 283(14): 2690-2700.

[227] Kawauchi K, Araki K, Tobiume K, Tanaka N. p53 regulates glucose metabolism through an IKK-NF-κB pathway and inhibits cell transformation. Nat Cell Biol. 2008; 10(5): 611-618.

[228] Karin M. NF-κB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol. 2009; 1(5): a000141.

[229] Bimová P, Barbieriková Z, Grenčíková A, et al. Environmental risk of nanomaterials and nanoparticles and EPR technique as an effective tool to study them—a review. Environmental Science and Pollution Research. 2021; 28: 22203-22220.

[230] Jiang W, Zhong S, Chen Z, et al. 2D-CuPd nanozyme overcome tamoxifen resistance in breast cancer by regulating the PI3K/AKT/mTOR pathway. Biomaterials. 2023; 294: 121986.

[231] Zhou H, Tang D, Yu Y, et al. Theranostic imaging and multimodal photodynamic therapy and immunotherapy using the mTOR signaling pathway. Nat Commun. 2023; 14(1): 5350.

[232] Wang X, Xiong T, Cui M, et al. A novel targeted co-delivery nanosystem for enhanced ovarian cancer treatment via multidrug resistance reversion and mTOR-mediated signaling pathway. Journal of Nanobiotechnology. 2021; 19(1): 444.

[233] Huang S, Wang K, Hua Z, Abd El-Aty A, Tan M. Size-controllable food-grade nanoparticles based on sea cucumber polypeptide with good anti-oxidative capacity to prolong lifespan in tumor-bearing mice. Int J Biol Macromol. 2023; 253: 127039.

[234] Yang Y, Zhang Z, Chen Q, You Y, Li X, Chen T. Functionalized selenium nanoparticles synergizes with metformin to treat breast cancer cells through regulation of selenoproteins. Front Bioeng Biotechnol. 2021; 9: 758482.

[235] Wang Y, Sun C, Huang L, et al. Magnolol-loaded cholesteryl biguanide conjugate hydrochloride nanoparticles for triple-negative breast cancer therapy. Int J Pharm. 2022; 615: 121509.

[236] Zhao Y, Wang W, Guo S, et al. PolyMetformin combines carrier and anticancer activities for in vivo siRNA delivery. Nat Commun. 2016; 7(1): 11822.

[237] Yagoub AEA, Alshammari GM, Subash-Babu P, Mohammed MAa, Yahya MA, Alhosain AI. Synthesis of Ziziphus spina-christi (Jujube) root methanol extract loaded functionalized silver nanoparticle (ZS-Ag-NPs); physiochemical characterization and effect of ZS-Ag-NPs on adipocyte maturation, adipokine and vascular smooth muscle cell interaction. Nanomaterials. 2021; 11(10): 2563.

[238] Deng X, Cao M, Zhang J, et al. Hyaluronic acid-chitosan nanoparticles for co-delivery of MiR-34a and doxorubicin in therapy against triple negative breast cancer. Biomaterials. 2014; 35(14): 4333-4344.

[239] Yang H, Li Y, Li T, et al. Multifunctional core/shell nanoparticles cross-linked polyetherimide-folic acid as efficient Notch-1 siRNA carrier for targeted killing of breast cancer. Sci Rep. 2014; 4(1): 7072.

[240] Sun J-H, Song S, Yang J-F. Oral administration of sea cucumber (Stichopus japonicus) protein exerts wound healing effects via the PI3K/AKT/mTOR signaling pathway. Food & Function. 2022; 13(19): 9796-9809.

[241] Green CL, Lamming DW, Fontana L. Molecular mechanisms of dietary restriction promoting health and longevity. Nat Rev Mol Cell Biol. 2022; 23(1): 56-73.

[242] Hofer SJ, Carmona-Gutierrez D, Mueller MI, Madeo F. The ups and downs of caloric restriction and fasting: from molecular effects to clinical application. EMBO Mol Med. 2022; 14(1): e14418.

[243] Napoleão A, Fernandes L, Miranda C, Marum AP. Effects of calorie restriction on health span and insulin resistance: classic calorie restriction diet vs. ketosis-inducing diet. Nutrients. 2021; 13(4): 1302.

[244] Mukherjee P, El-Abbadi M, Kasperzyk J, Ranes M, Seyfried T. Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. Br J Cancer. 2002; 86(10): 1615-1621.

[245] Lee C, Longo V. Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients. Oncogene. 2011; 30(30): 3305-3316.

[246] Acosta-Rodríguez V, Rijo-Ferreira F, Izumo M, et al. Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice. Science. 2022; 376(6598): 1192-1202.

[247] Martel J, Ojcius DM, Ko YF, Chang CJ, Young JD. Antiaging effects of bioactive molecules isolated from plants and fungi. Med Res Rev. 2019; 39(5): 1515-1552.

[248] Brandhorst S, Longo VD. Fasting and caloric restriction in cancer prevention and treatment. Metabolism in cancer. 2016: 241-266.

[249] Kirkham AA, King K, Joy AA, et al. Rationale and design of the diet restriction and exercise-induced adaptations in metastatic breast cancer (DREAM) study: a 2-arm, parallel-group, phase II, randomized control trial of a short-term, calorie-restricted, and ketogenic diet plus exercise during intravenous chemotherapy versus usual care. BMC Cancer. 2021; 21: 1-14.

[250] Sundfør T, Svendsen M, Tonstad S. Effect of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk: a randomized 1-year trial. Nutr Metab Cardiovasc Dis. 2018; 28(7): 698-706.

[251] Zeng X, Li H, Jiang W, et al. Phytochemical compositions, health-promoting properties and food applications of crabapples: a review. Food Chem. 2022; 386: 132789.

[252] Craig WJ, Mangels AR, Fresán U, et al. The safe and effective use of plant-based diets with guidelines for health professionals. Nutrients. 2021; 13(11): 4144.

[253] Motallebi M, Bhia M, Rajani HF, et al. Naringenin: a potential flavonoid phytochemical for cancer therapy. Life Sci. 2022; 305: 120752.

[254] Iman M, Taheri M, Bahari Z. The anti-cancer properties of neem (Azadirachta indica) through its antioxidant activity in the liver: its pharmaceutics and toxic dosage forms. A literature review. Journal of Complementary and Integrative Medicine. 2022; 19(2): 203-211.

[255] Glorieux C, Calderon PB. Catalase, a remarkable enzyme: targeting the oldest antioxidant enzyme to find a new cancer treatment approach. Biol Chem. 2017; 398(10): 1095-1108.

[256] Dobros N, Zawada KD, Paradowska K. Phytochemical profiling, antioxidant and anti-inflammatory activity of plants belonging to the Lavandula genus. Molecules. 2022; 28(1): 256.

[257] Kubo A, Corley DA, Jensen CD, Kaur R. Dietary factors and the risks of oesophageal adenocarcinoma and Barrett’s oesophagus. Nutr Res Rev. 2010; 23(2): 230-246.

[258] Ngo B, Van Riper JM, Cantley LC, Yun J. Targeting cancer vulnerabilities with high-dose vitamin C. Nat Rev Cancer. 2019; 19(5): 271-282.

[259] Ratanasrimetha P, Workeneh BT, Seethapathy H. Sodium and potassium dysregulation in the patient with cancer. Adv Chronic Kidney Dis. 2022; 29(2): 171-179. e1.

[260] Mendes PMV, Bezerra DLC, Dos Santos LR, et al. Magnesium in breast cancer: what is its influence on the progression of this disease? Biol Trace Elem Res. 2018; 184: 334-339.

[261] Rowles III JL, Erdman Jr JW. Carotenoids and their role in cancer prevention. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 2020; 1865(11): 158613.

[262] Santamaria L, Bianchi A. Cancer chemoprevention by supplemental carotenoids in animals and humans. Prev Med. 1989; 18(5): 603-623.

[263] Milani A, Basirnejad M, Shahbazi S, Bolhassani A. Carotenoids: biochemistry, pharmacology and treatment. Br J Pharmacol. 2017; 174(11): 1290-1324.

[264] Mrowicka M, Mrowicki J, Kucharska E, Majsterek I. Lutein and zeaxanthin and their roles in age-related macular degeneration—neurodegenerative disease. Nutrients. 2022; 14(4): 827.

[265] Al-Farsi MA, Lee CY. Nutritional and functional properties of dates: a review. Crit Rev Food Sci Nutr. 2008; 48(10): 877-887.

[266] Biver E, Herrou J, Larid G, et al. Dietary recommendations in the prevention and treatment of osteoporosis. Joint Bone Spine. 2023; 90(3): 105521.

[267] McCubrey JA, Lertpiriyapong K, Steelman LS, et al. Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs. Aging (Albany NY). 2017; 9(6): 1477.

[268] Baur JA. Biochemical effects of SIRT1 activators. Biochimica et Biophysica Acta (Bba)-Proteins and Proteomics. 2010; 1804(8): 1626-1634.

[269] Wang X, Zhang W, Zhou S. Multifaceted physiological and therapeutical impact of curcumin on hormone-related endocrine dysfunctions: a comprehensive review. Phytother Res. 2024; 38(7): 3307-3336

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