Published 6 issues per year
ISSN Print: 1045-4403
ISSN Online: 2162-6502
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mTOR, AMPK, and Sirt1: Key Players in Metabolic Stress Management
ABSTRACT
Cells adapt their metabolism and activities in response to signals from their surroundings, and this ability is essential for their survival in the face of environmental changes. In mammalian tissues a deficit of these mechanisms is commonly associated with cellular aging and degenerative diseases related to aging, such as cardiovascular disease, cancer, immune system decline, and neurological pathologies. Several proteins have been identified as able to respond directly to energy, nutrient, and growth factor levels and stress stimuli in order to mediate adaptations in the cell. Many of these proteins are enzymes that positively or negatively modulate the autophagic process. This review focuses on biochemical mechanisms involving enzymes−specifically, mTOR, AMPK, and Sirt1−that are currently considered important for these adaptive responses, providing an overview of the interactions of the main players in this process.
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Das Sunetra, Pitts Natalie L., Mudron Megan R., Durica David S., Mykles Donald L., Transcriptome analysis of the molting gland (Y-organ) from the blackback land crab, Gecarcinus lateralis, Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 17, 2016. Crossref
-
Ma Lijie, Zhao Yilin, Wang Ruixuan, Chen Tingting, Li Wangping, Nan Yandong, Liu Xueying, Jin Faguang, 3,5,4′-Tri-O-acetylresveratrol Attenuates Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome via MAPK/SIRT1 Pathway, Mediators of Inflammation, 2015, 2015. Crossref
-
Abuhagr Ali M., MacLea Kyle S., Mudron Megan R., Chang Sharon A., Chang Ernest S., Mykles Donald L., Roles of mechanistic target of rapamycin and transforming growth factor-β signaling in the molting gland (Y-organ) of the blackback land crab, Gecarcinus lateralis, Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 198, 2016. Crossref
-
Vaiserman A.M., Anti-Aging Drugs, in Comprehensive Medicinal Chemistry III, 2017. Crossref
-
Ghisalberti Carlo A., Borzì Rosa M., Cetrullo Silvia, Flamigni Flavio, Cairo Gaetano, Soft TCPTP Agonism—Novel Target to Rescue Airway Epithelial Integrity by Exogenous Spermidine, Frontiers in Pharmacology, 7, 2016. Crossref
-
Vaiserman Alexander M., Lushchak Oleh V., Koliada Alexander K., Anti-aging pharmacology: Promises and pitfalls, Ageing Research Reviews, 31, 2016. Crossref
-
Cetrullo Silvia, D'Adamo Stefania, Guidotti Serena, Borzì Rosa Maria, Flamigni Flavio, Hydroxytyrosol prevents chondrocyte death under oxidative stress by inducing autophagy through sirtuin 1-dependent and -independent mechanisms, Biochimica et Biophysica Acta (BBA) - General Subjects, 1860, 6, 2016. Crossref
-
Liu Xiangwei, Ren Jun, Role of Mammalian Target of Rapamycin (mTOR) in Cardiac Homeostasis in Metabolic Disorders, in Molecules to Medicine with mTOR, 2016. Crossref
-
Yang Jai-Sing, Lu Chi-Cheng, Kuo Sheng-Chu, Hsu Yuan-Man, Tsai Shih-Chang, Chen Shih-Yin, Chen Yng-Tay, Lin Ying-Ju, Huang Yu-Chuen, Chen Chao-Jung, Lin Wei-De, Liao Wen-Lin, Lin Wei-Yong, Liu Yu-Huei, Sheu Jinn-Chyuan, Tsai Fuu-Jen, Autophagy and its link to type II diabetes mellitus, BioMedicine, 7, 2, 2017. Crossref
-
Lin Xiao-Long, Liu Yuanbo, Liu Mihua, Hu HuiJun, Pan Yongquan, Fan Xiao-Juan, Hu Xue-Mei, Zou Wei-Wen, Inhibition of Hydrogen Peroxide-Induced Human Umbilical Vein Endothelial Cells Aging by Allicin Depends on Sirtuin1 Activation, Medical Science Monitor, 23, 2017. Crossref
-
Lushchak Oleh, Strilbytska Olha, Piskovatska Veronika, Storey Kenneth B., Koliada Alexander, Vaiserman Alexander, The role of the TOR pathway in mediating the link between nutrition and longevity, Mechanisms of Ageing and Development, 164, 2017. Crossref
-
Sun Wai Yan, Wang Yu, Calorie Restriction Mimetics From Functional Foods, in Nutrition and Functional Foods for Healthy Aging, 2017. Crossref
-
D’Adamo Stefania, Cetrullo Silvia, Minguzzi Manuela, Silvestri Ylenia, Borzì Rosa Maria, Flamigni Flavio, MicroRNAs and Autophagy: Fine Players in the Control of Chondrocyte Homeostatic Activities in Osteoarthritis, Oxidative Medicine and Cellular Longevity, 2017, 2017. Crossref
-
Piskovatska Veronika, Strilbyska Olha, Storey Kenneth B., Vaiserman Alexander M., Lushchak Oleh, mTOR Pharmacology, in Reference Module in Biomedical Sciences, 2018. Crossref
-
Minguzzi Manuela, Cetrullo Silvia, D’Adamo Stefania, Silvestri Ylenia, Flamigni Flavio, Borzì Rosa Maria, Emerging Players at the Intersection of Chondrocyte Loss of Maturational Arrest, Oxidative Stress, Senescence and Low-Grade Inflammation in Osteoarthritis, Oxidative Medicine and Cellular Longevity, 2018, 2018. Crossref
-
Zhang Huaping, Yang Xiaorong, Pang Xuefen, Zhao Zhenxiang, Yu Haixia, Zhou Hui, Genistein protects against ox-LDL-induced senescence through enhancing SIRT1/LKB1/AMPK-mediated autophagy flux in HUVECs, Molecular and Cellular Biochemistry, 455, 1-2, 2019. Crossref
-
Jiang Xiaona, Xue Songyi, Kang Tingting, Liu Huijing, Ren Huihui, Hua Renwu, Ni Debin, Lei Minggang, Annexin A8 (ANXA8 ) regulates proliferation of porcine endometrial cells via Akt signalling pathway, Reproduction in Domestic Animals, 54, 1, 2019. Crossref
-
Nguyen Long T., Chen Hui, Pollock Carol A., Saad Sonia, Sirtuins—mediators of maternal obesity‐induced complications in offspring?, The FASEB Journal, 30, 4, 2016. Crossref
-
Qiu Haowen, Schlegel Vicki, Impact of nutrient overload on metabolic homeostasis, Nutrition Reviews, 76, 9, 2018. Crossref
-
Wu Kejia, Tian Rui, Huang Jing, Yang Yongqiang, Dai Jie, Jiang Rong, Zhang Li, Metformin alleviated endotoxemia-induced acute lung injury via restoring AMPK-dependent suppression of mTOR, Chemico-Biological Interactions, 291, 2018. Crossref
-
Khatami Mahin, Theories of Aging and Chronic Diseases: Chronic Inflammation an Interdependent ‘Roadmap’ to Age-Associated Illnesses, in Inflammation, Aging and Cancer, 2017. Crossref
-
Neto Jessika Geisebel Oliveira, Boechat Silvia Karl, Romão Juliana Santos, Pazos-Moura Carmen Cabanelas, Oliveira Karen Jesus, Treatment with cinnamaldehyde reduces the visceral adiposity and regulates lipid metabolism, autophagy and endoplasmic reticulum stress in the liver of a rat model of early obesity, The Journal of Nutritional Biochemistry, 77, 2020. Crossref
-
Faivre Sandrine, Neuzillet Cindy, Raymond Eric, Predictive Biomarkers of Response to mTOR Inhibitors, in mTOR Inhibition for Cancer Therapy: Past, Present and Future, 2016. Crossref
-
Carloni Silvia, Balduini Walter, Simvastatin preconditioning confers neuroprotection against hypoxia-ischemia induced brain damage in neonatal rats via autophagy and silent information regulator 1 (SIRT1) activation, Experimental Neurology, 324, 2020. Crossref
-
Wang Xiangming, Zhao Li, Ajay Amrendra K., Jiao Baihai, Zhang Xianhui, Wang Chunguo, Gao Xue, Yuan Zhongyu, Liu Hongfang, Liu Wei Jing, QiDiTangShen Granules Activate Renal Nutrient-Sensing Associated Autophagy in db/db Mice, Frontiers in Physiology, 10, 2019. Crossref
-
Huang Jun, Wang Xue, Zhu Yi, Li Zhe, Zhu Yu‐Ting, Wu Jun‐Chao, Qin Zheng‐Hong, Xiang Min, Lin Fang, Exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway, CNS Neuroscience & Therapeutics, 25, 6, 2019. Crossref
-
Ribeiro Diego Luís, Machado Ana Rita Thomazela, da Silva Machado Carla, Santos Patrick Wellington da Silva, Aissa Alexandre Ferro, Barcelos Gustavo Rafael Mazzaron, Antunes Lusânia Maria Greggi, Analysis of the cytotoxic, genotoxic, mutagenic, and pro-oxidant effect of synephrine, a component of thermogenic supplements, in human hepatic cells in vitro, Toxicology, 422, 2019. Crossref
-
Zhang Hong, Song Yuanchun, Rong Wei, Fan Linxia, Cai Yufeng, Qu Qiang, Gao Yun, Zhao Hongxia, miR-221 participates in the airway epithelial cells injury in asthma via targeting SIRT1, Experimental Lung Research, 44, 6, 2018. Crossref
-
Wang Jia-Mei, Liu Bao-Qin, Li Chao, Du Zhen-Xian, Sun Jia, Yan Jing, Jiang Jing-Yi, Wang Hua-Qin, Sestrin 2 protects against metabolic stress in a p53-independent manner, Biochemical and Biophysical Research Communications, 513, 4, 2019. Crossref
-
Yu Yinghao, Zhao Jijun, Modulated Autophagy by MicroRNAs in Osteoarthritis Chondrocytes, BioMed Research International, 2019, 2019. Crossref
-
Laws Maxwell T, Bonomi Robin E, Gelovani David J, Llaniguez Jeremy, Lu Xin, Mangner Thomas, Gelovani Juri G, Noninvasive quantification of SIRT1 expression–activity and pharmacologic inhibition in a rat model of intracerebral glioma using 2-[18F]BzAHA PET/CT/MRI, Neuro-Oncology Advances, 2, 1, 2020. Crossref
-
Hsu Chien-Ning, Tain You-Lin, Amino Acids and Developmental Origins of Hypertension, Nutrients, 12, 6, 2020. Crossref
-
Li Chuntao, Liu Zhixiong, Yang Kui, Chen Xin, Zeng Yu, Liu Jinfang, Li Zhenyan, Liu Yunsheng, miR-133b inhibits glioma cell proliferation and invasion by targeting Sirt1, Oncotarget, 7, 24, 2016. Crossref
-
Wang Hai-Long, Tang Fu-Qin, Jiang Yun-Han, Zhu Yu, Jian Zhao, Xiao Ying-Bin, AMPKα2 deficiency exacerbates hypoxia-induced pulmonary hypertension by promoting pulmonary arterial smooth muscle cell proliferation, Journal of Physiology and Biochemistry, 76, 3, 2020. Crossref
-
Bauer M., Wetzker R., The cellular basis of organ failure in sepsis—signaling during damage and repair processes, Medizinische Klinik - Intensivmedizin und Notfallmedizin, 115, S1, 2020. Crossref
-
Park Ji Eun, Lee Heaji, Kim Sun Yeou, Lim Yunsook, Lespedeza bicolor Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice, Antioxidants, 9, 2, 2020. Crossref
-
Hong Yu Ah, Kim Ji Eun, Jo Minjee, Ko Gang-Jee, The Role of Sirtuins in Kidney Diseases, International Journal of Molecular Sciences, 21, 18, 2020. Crossref
-
Santos Milena Almeida, Franco Filipe Nogueira, Caldeira Camila Amaro, de Araújo Glaucy Rodrigues, Vieira Alessandra, Chaves Miriam Martins, Lara Raquel Cunha, Antioxidant effect of Resveratrol: Change in MAPK cell signaling pathway during the aging process, Archives of Gerontology and Geriatrics, 92, 2021. Crossref
-
Yin Qin, Wang Jin-Feng, Xu Xiao-Hua, Xie Hong, Effect of lycopene on pain facilitation and the SIRT1/mTOR pathway in the dorsal horn of burn injury rats, European Journal of Pharmacology, 889, 2020. Crossref
-
Lama Stefania, Monda Vincenzo, Rizzo Maria Rosaria, Dacrema Marco, Maisto Maria, Annunziata Giuseppe, Tenore Gian Carlo, Novellino Ettore, Stiuso Paola, Sartiani Laura, Cardioprotective Effects of Taurisolo® in Cardiomyoblast H9c2 Cells under High-Glucose and Trimethylamine N-Oxide Treatment via De Novo Sphingolipid Synthesis, Oxidative Medicine and Cellular Longevity, 2020, 2020. Crossref
-
Pignatti Carla, D’Adamo Stefania, Stefanelli Claudio, Flamigni Flavio, Cetrullo Silvia, Nutrients and Pathways that Regulate Health Span and Life Span, Geriatrics, 5, 4, 2020. Crossref
-
Ribeiro Diego Luis, Machado Ana Rita Thomazela, Machado Carla, Ferro Aissa Alexandre, Dos Santos Patrick Wellington, Barcelos Gustavo Rafael Mazzaron, Antunes Lusânia Maria Greggi, p-synephrine induces transcriptional changes via the cAMP/PKA pathway but not cytotoxicity or mutagenicity in human gastrointestinal cells, Journal of Toxicology and Environmental Health, Part A, 84, 5, 2021. Crossref
-
Carapeto Priscila Viana, Aguayo-Mazzucato Cristina, Effects of exercise on cellular and tissue aging, Aging, 13, 10, 2021. Crossref
-
Faria João, Gerritsen Karin G.F., Nguyen Tri Q., Mihaila Silvia M., Masereeuw Rosalinde, Diabetic proximal tubulopathy: Can we mimic the disease for in vitro screening of SGLT inhibitors?, European Journal of Pharmacology, 908, 2021. Crossref
-
Maldonado Martin, Chen Jianying, Lujun Yang, Duan Huiqin, Raja Mazhar Ali, Qu Ting, Huang Tianhua, Gu Jiang, Zhong Ying, The consequences of a high-calorie diet background before calorie restriction on skeletal muscles in a mouse model, Aging, 13, 12, 2021. Crossref
-
Chen Chen, Ma Jiulong, Miao Chun Sheng, Zhang Huayu, Zhang Ming, Cao Xia, Shi Yan, Trigonelline induces autophagy to protect mesangial cells in response to high glucose via activating the miR-5189-5p-AMPK pathway, Phytomedicine, 92, 2021. Crossref
-
Horvath Matej, Mihajlovic Zorana, Slaninova Vera, Perez-Gomez Raquel, Moshkin Yuri, Krejci Alena, The silent information regulator 1 (Sirt1) is a positive regulator of the Notch pathway in Drosophila , Biochemical Journal, 473, 22, 2016. Crossref
-
Zou Yunyi, Chen Zhanglin, Sun Chenchen, Yang Dong, Zhou Zuoqiong, Peng Xiyang, Zheng Lan, Tang Changfa, Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling, International Journal of Molecular Sciences, 22, 20, 2021. Crossref
-
Fardous Ali M., Beydoun Safa, James Andrew A., Ma Hongzhi, Cabelof Diane C., Unnikrishnan Archana, Heydari Ahmad R., The Timing and Duration of Folate Restriction Differentially Impacts Colon Carcinogenesis, Nutrients, 14, 1, 2021. Crossref
-
Ukraintseva Svetlana, Duan Matt, Arbeev Konstantin, Wu Deqing, Bagley Olivia, Yashkin Arseniy P., Gorbunova Galina, Akushevich Igor, Kulminski Alexander, Yashin Anatoliy, Interactions Between Genes From Aging Pathways May Influence Human Lifespan and Improve Animal to Human Translation, Frontiers in Cell and Developmental Biology, 9, 2021. Crossref
-
Gao Feng, Zhao Yongcheng, Zhang Bin, Xiao Chunwei, Sun Zhanfa, Gao Yuan, Dou Xueyong, SESN1 attenuates the Ox‑LDL‑induced inflammation, apoptosis and endothelial‑mesenchymal transition of human umbilical vein endothelial cells by regulating AMPK/SIRT1/LOX1 signaling, Molecular Medicine Reports, 25, 5, 2022. Crossref
-
Mousavi Seyed Mojtaba, Derakhshan Maryam, Baharloii Fatereh, Dashti Fatemeh, Mirazimi Seyed Mohammad Ali, Mahjoubin-Tehran Maryam, Hosseindoost Saereh, Goleij Pouya, Rahimian Neda, Hamblin Michael R., Mirzaei Hamed, Non-coding RNAs and glioblastoma: Insight into their roles in metastasis, Molecular Therapy - Oncolytics, 24, 2022. Crossref
-
McCarty Mark F., Lewis Lujan Lidianys, Iloki Assanga Simon, Targeting Sirt1, AMPK, Nrf2, CK2, and Soluble Guanylate Cyclase with Nutraceuticals: A Practical Strategy for Preserving Bone Mass, International Journal of Molecular Sciences, 23, 9, 2022. Crossref
-
Voevodin Andrey A., Khadartsev Alexander A., Bondar Stanislav S., Terekhov Igor V., Nikiforov Victor S., The State of Intracellular Molecular Regulators during the Reconvalescence of Community-Acquired Pneumonia under the Influence of Microwaves at 1 GHz, Integrative Medicine International, 4, 3-4, 2018. Crossref
-
D'Adamo S., Cetrullo S., Guidotti S., Borzì R.M., Flamigni F., Hydroxytyrosol modulates the levels of microRNA-9 and its target sirtuin-1 thereby counteracting oxidative stress-induced chondrocyte death, Osteoarthritis and Cartilage, 25, 4, 2017. Crossref
-
Ma Ning, Li Xin, Wang Hong-bin, Gao Li, Xiao Jian-hua, Effects of tiletamine-xylazine-tramadol combination and its specific antagonist on AMPK in the brain of rats, Journal of Veterinary Research, 63, 2, 2019. Crossref
-
Sui Xiukun, Wang Hailong, Wu Feng, Yang Chao, Zhang Hongyu, Xu Zihan, Guo Yaxiu, Guo ZhiFeng, Xin Bingmu, Ma Ting, Li Yinghui, Dai Zhongquan, Hepatic metabolite responses to 4-day complete fasting and subsequent refeeding in rats, PeerJ, 10, 2022. Crossref
-
Wang Feiran, Song Jian, Yan Yingying, Zhou Qian, Li Xiaojing, Wang Ping, Yang Zongtong, Zhang Qiuhong, Zhang Huimin, Integrated Network Pharmacology Analysis and Serum Metabolomics to Reveal the Anti-malaria Mechanism of Artesunate, ACS Omega, 7, 35, 2022. Crossref
-
Zhao Li, Zhao Tianyi, Yang Xue, Cao Ling, Xu Rui, Liu Jiyu, Lin Cong, Yu Yiyun, Xuan Dandan, Zhu Xiaoxia, Liu Lei, Hua Yinghui, Deng Chunhui, Wan Weiguo, Zou Hejian, Xue Yu, IL-37 blocks gouty inflammation by shaping macrophages into a non-inflammatory phagocytic phenotype, Rheumatology, 61, 9, 2022. Crossref
-
Lara Raquel Cunha, Franco Filipe Nogueira, de Araújo Glaucy Rodrigues, Silva Barbara Nellita Moura, Chaves Miriam Martins, The preventive use of resveratrol increases its antioxidant effect by SIRT1 and subclinical anti-inflammatory action in Neuro-2A cells, In Vitro Cellular & Developmental Biology - Animal, 58, 10, 2022. Crossref
-
Zhang Ziyuan, Fang Jingai, Sun Dalin, Zheng Yaqin, Liu Xinhui, Li Hui, Hu Yaling, Liu Yuxiang, Zhang Mingyu, Liu Wenyuan, Zhang Xiaodong, Liu Xuejun, Khan Haroon, Study on the Mechanism of Radix Astragali against Renal Aging Based on Network Pharmacology, Evidence-Based Complementary and Alternative Medicine, 2022, 2022. Crossref
-
Yang Lili, Nutrient sensing and aging, in Molecular, Cellular, and Metabolic Fundamentals of Human Aging, 2023. Crossref