Metabolic features and regulation in cell senescence

Kwon, So Mee; Hong, Sun Mi; Lee, Young-Kyoung; Min, Seongki; Yoon, Gyesoon

doi:10.5483/bmbrep.2019.52.1.291

Cited by 111Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsSirtuins and Resveratrol in Medicine

Metabolic features and regulation in cell senescence

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Kwon, So Mee, Hong, Sun Mi, Lee, Young-Kyoung, Min, Seongki, Yoon, Gyesoon·2019·BMB Reports

DOI 10.5483/bmbrep.2019.52.1.291PMC PMC6386228

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Abstract

Organismal aging is accompanied by a host of progressive metabolic alterations and an accumulation of senescent cells, along with functional decline and the appearance of multiple diseases. This implies that the metabolic features of cell senescence may contribute to the organism's metabolic changes and be closely linked to age-associated diseases, especially metabolic syndromes. However, there is no clear understanding of senescent metabolic characteristics. Here, we review key metabolic features and regulators of cellular senescence, focusing on mitochondrial dysfunction and anabolic deregulation, and their link to other senescence phenotypes and aging. We further discuss the mechanistic involvement of the metabolic regulators mTOR, AMPK, and GSK3, proposing them as key metabolic switches for modulating senescence. [BMB Reports 2019; 52(1): 5-12].

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In some respects, senescent cells resemble non-dividing cancer cells, including apoptosis resistance and metabolic shifts.
“In some respects, senescent cells are like non-dividing cancer cells, including apoptosis resistance and metabolic shifts [7, 11, 28, 57–59].”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [57]
Pathogenic mtDNA has been reported to participate in cellular senescence.
“Furthermore, pathogenic mtDNA has also been reported to be involved in cellular senescence99.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [99]

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“Several upstream regulators of SREBP1, including GSK3, AMPK, and mTOR, regulate senescence and/or aging (76-79), indicating SREBP1-mediated”
Background
A new player in the orchestra of cell growth: SREBP activity is regulated by mTORC1 and contributes to the regulation of cell and organ size
Porstmann, T., Santos, C. R., Lewis, C. A., Griffiths, B. L., & Schulze, A. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370278 · Cited by 92 · cited 1× · see citing works
“Lipid biosynthesis, called lipogenesis, is mainly increased during cell proliferation to provide sufficient subcellular organelles for progenies (72, 73).”
Background
Complex II Defect via Down-regulation of Iron-Sulfur Subunit Induces Mitochondrial Dysfunction and Cell Cycle Delay in Iron Chelation-induced Senescence-associated Growth Arrest
Yoon, Y.-S., Byun, H.-O., Cho, H., Kim, B.-K., & Yoon, G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308489200 · Cited by 91 · cited 1× · see citing works
“senescence in Chang normal liver cells (21, 22).”
BackgroundSelf-citation
Longevity Pathways (mTOR, SIRT, Insulin/IGF-1) as Key Modulatory Targets on Aging and Neurodegeneration.
Mazucanti, C., Cabral-Costa, J. V., Vasconcelos, A., Andreotti, D., Scavone, C., & Kawamoto, E. (2015) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026615666150610125715 · Cited by 89 · cited 1× · see citing works
“2) (90), emphasizing the three regulators of proteasis and senescence.”
Background
Studies on giant mitochondria
TANDLER, B., & HOPPEL, C. L. (1986) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1986.tb46548.x · Cited by 89 · cited 1× · see citing works
“or highly interconnected mitochondria have often been reported in cirrhotic livers and in several aged tissues (28, 29).”
Background
Enhanced glycogenesis is involved in cellular senescence via GSK3/GS modulation
Seo, Y., Jung, H., Shin, H., Kim, Y., Yim, H., Chung, H., Lim, I. K., & Yoon, G. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00436.x · Cited by 86 · cited 3× · see citing works
“aggregates in several cell senescence systems, including replicative senescence of primary human fibroblasts (62), is a new component of senescent granules (Fig.”
BackgroundSelf-citation
Erratum to: From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes
Byun, H., Lee, Y., Kim, J., & Yoon, G. (2016) · BMB Reports · doi:10.5483/bmbrep.2016.49.11.122 · Cited by 83 · see citing works
Self-citation
Mitochondrial DNA Mutations and Aging
Krishnan, K. J., Greaves, L. C., Reeve, A. K., & Turnbull, D. M. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1395.024 · Cited by 79 · cited 1× · see citing works
“deletions or mutations have been associated with aging and certain age-related diseases in animals (14-16).”
Background
Energy Homeostasis and Cancer Prevention: The AMP-Activated Protein Kinase
Fay, J. R., Steele, V. E., & Crowell, J. A. (2009) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-08-0166 · Cited by 78 · cited 1× · see citing works
“translation either through inhibiting mTOR or eEF2 (86), and activates autophagy through ULK phosphorylation (87).”
Background
Iron chelation-induced senescence-like growth arrest in hepatocyte cell lines: association of transforming growth factor β1 (TGF-β1)-mediated p27Kip1 expression
Yoon, G., Kim, H. J., Yoon, Y., Cho, H., Lim, I. K., & Lee, J. (2002) · Biochemical Journal · doi:10.1042/bj20011445 · Cited by 77 · see citing works
Self-citation
Telomere-driven replicative senescence is a stress response
von Zglinicki, T., Petrie, J., & Kirkwood, T. B. L. (2003) · Nature Biotechnology · doi:10.1038/nbt0303-229b · Cited by 76 · cited 1× · see citing works
“A direct link between mitochondrial dysfunction and telomere attrition was demonstrated using replicative senescence of MRF5 human fibroblasts (57, 58).”
Background
GSK3 Inactivation Is Involved in Mitochondrial Complex IV Defect in Transforming Growth Factor (TGF) Β1-Induced Senescence
Byun, H.-O., Jung, H.-J., Seo, Y.-H., Lee, Y.-K., Hwang, S.-C., Seong Hwang, E., & Yoon, G. (2012) · Experimental Cell Research · doi:10.1016/j.yexcr.2012.04.012 · Cited by 66 · cited 2× · see citing works
“Moreover, GSK3 inactivation can cause mitochondrial OXPHOS dysfunction and increase ROS by inhibiting complex IV activity (25).”
BackgroundSelf-citation
Mitochondrial stress induces cellular senescence in an mTORC1-dependent manner
Nacarelli, T., Azar, A., & Sell, C. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.03.008 · Cited by 58 · see citing works
Downregulation of peroxiredoxin-3 by hydrophobic bile acid induces mitochondrial dysfunction and cellular senescence in human trophoblasts
Wu, W., Menon, R., Xu, Y.-Y., Zhao, J.-R., Wang, Y.-L., Liu, Y., & Zhang, H.-J. (2016) · Scientific Reports · doi:10.1038/srep38946 · Cited by 46 · cited 1× · see citing works
“Mitochondrial dysfunction was also involved in hydrophobic bile acid-induced human trophoblasts (27).”
Background
Differing effects of rapamycin and mTOR kinase inhibitors on protein synthesis
Huo, Y., Iadevaia, V., & Proud, C. G. (2011) · Biochemical Society Transactions · doi:10.1042/bst0390446 · Cited by 45 · cited 1× · see citing works
“The negative regulator of autophagy, mTOR, activates translation machinery by activating eIF4E, eIF4B, and eEF2, and regulates senescence (83-85).”
Background
Glycogen accumulation of the aging human brain
Gertz, H., Cervós‐Navarro, J., Frýdl, V., & Schultz, F. (1985) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(85)90024-7 · Cited by 45 · see citing works
4-Hydroxynonenal inhibits telomerase activity and hTERT expression in human leukemic cell lines
Pizzimenti, S., Briatore, F., Laurora, S., Toaldo, C., Maggio, M., Grandi, M. D., Meaglia, L., Menegatti, E., Giglioni, B., Dianzani, M. U., et al. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.12.024 · Cited by 44 · see citing works
The Interorganellar Interaction between Distinct Human Mitochondria with Deletion Mutant mtDNA from a Patient with Mitochondrial Disease and with HeLa mtDNA
Takai, D., Inoue, K., Goto, Y., Nonaka, I., & Hayashi, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.9.6028 · Cited by 43 · cited 1× · see citing works
“and to preserve the function of randomly damaged individual mitochondrion (33, 34).”
Background
Roles of GSK3 in metabolic shift toward abnormal anabolism in cell senescence
Kim, Y., Seo, Y., Park, C., Yoon, S., & Yoon, G. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05617.x · Cited by 41 · cited 1× · see citing works
“The phosphorylated GSK3 activates anabolism via SREBP1-mediated lipogenesis, eIF2B-mediated translation, and GS-mediated glycogenesis (93).”
BackgroundSelf-citation
Cellular aging of mitochondrial DNA-depleted cells
Park, S. Y., Choi, B., Cheon, H., Pak, Y. K., Kulawiec, M., Singh, K. K., & Lee, M. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.10.182 · Cited by 39 · cited 2× · see citing works
“Mitochondrial DNA-depleted rho(0) MDA-MB-435 cells displayed senescent phenotypes, such as SA--Gal, lipofuscin pigment, and decreased telomerase activity (20).”
Background
Glycogen accumulation in tibial nerves of experimentally diabetic and aging control rats
Moore, S. A., Peterson, R. G., Felten, D. L., & O’Connor, B. L. (1981) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(81)90012-5 · Cited by 37 · cited 1× · see citing works
“granules have also been shown to accumulate in myelinated axons (66) and liver tissues of aged rats (62), and formed inclusion bodies in the cerebral cortex of people over 60 years”
Background
Beyond retrograde and anterograde signalling: mitochondrial–nuclear interactions as a means for evolutionary adaptation and contemporary disease susceptibility
Ballinger, S. W. (2013) · Biochemical Society Transactions · doi:10.1042/bst20120227 · Cited by 31 · cited 1× · see citing works
“such as cancer, neurodegeneration, and cardiovascular diseases (39-41).”
Background
Dissecting the role of mTOR complexes in cellular senescence
Serrano, M. (2012) · Cell Cycle · doi:10.4161/cc.21065 · Cited by 30 · cited 1× · see citing works
“The negative regulator of autophagy, mTOR, activates translation machinery by activating eIF4E, eIF4B, and eEF2, and regulates senescence (83-85).”
Background
Mitochondrial alterations in aged rat adrenal cortical cells.
Murakoshi, M., Osamura, Y., & Watanabe, K. (1985) · PubMed · Cited by 22 · see citing works
Glycogen Synthase Kinase 3 Inactivation Induces Cell Senescence through Sterol Regulatory Element Binding Protein 1-Mediated Lipogenesis in Chang Cells
Kim, Y., Song, I., Seo, Y., & Yoon, G. (2013) · Endocrinology and Metabolism · doi:10.3803/enm.2013.28.4.297 · Cited by 21 · cited 1× · see citing works
“Several upstream regulators of SREBP1, including GSK3, AMPK, and mTOR, regulate senescence and/or aging (76-79), indicating SREBP1-mediated”
BackgroundSelf-citation
PKCδ phosphorylation is an upstream event of GSK3 inactivation-mediated ROS generation in TGF-β1-induced senescence
Byun, H., Jung, H.-J., Kim, M.-J., & Yoon, G. (2014) · Free Radical Research · doi:10.3109/10715762.2014.929120 · Cited by 21 · see citing works
Self-citation
Galantamine alleviates senescence of U87 cells induced by beta-amyloid through decreasing ROS production
Zhang, Y., Zhao, L., Wu, Z., Chen, X., & Ma, T. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.05.055 · Cited by 17 · see citing works
Mechanism and Physiological Significance of Growth Factor-Related Autophagy
Li, T. Y., Lin, S., & Lin, S. (2013) · Physiology · doi:10.1152/physiol.00023.2013 · Cited by 15 · cited 2× · see citing works
“Simultaneously, the inactivated GSK3 inhibits autophagy through the TIP60/ULK axis (89).”
Background

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Mitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990 · see citing works
Mitochondrial Homeostasis and Cellular Senescence
Vasileiou, P. V. S., Evangelou, K., Vlasis, K. G., Fildisis, G., Panayiotidis, M. I., Chronopoulos, E., Passias, P.-G., Kouloukoussa, M., Gorgoulis, V. G., & Havaki, S. (2019) · Cells · doi:10.3390/cells8070686 · Cited by 246 · see citing works
“Noteworthy, mitochondrial deoxyribonucleic acid (mtDNA) is highly vulnerable to ROS due to proximity to the generation site, whilst damaged mtDNA in turn, impairs OXPHOS function, thus further enhancing ROS release [17].”
Background
Reducing Senescent Cell Burden in Aging and Disease
Pignolo, R. J., Passos, J. F., Khosla, S., Tchkonia, T., & Kirkland, J. L. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.03.005 · Cited by 177 · see citing works
Telomeres and Mitochondrial Metabolism: Implications for Cellular Senescence and Age-related Diseases
Gao, X., Yu, X., Zhang, C., Wang, Y., Sun, Y., Sun, H., Zhang, H., Shi, Y., & He, X. (2022) · Stem Cell Reviews and Reports · doi:10.1007/s12015-022-10370-8 · Cited by 180 · see citing works
Cell Senescence, DNA Damage, and Metabolism
Shmulevich, R., & Krizhanovsky, V. (2021) · Antioxidants & Redox Signaling · doi:10.1089/ars.2020.8043 · Cited by 157 · see citing works
“Changes in mitochondrial OXPHOS are primarily associated with early stages of cellular senescence (50).”
Cellular Senescence and Ageing: Mechanisms and Interventions
Mylonas, A., & O’Loghlen, A. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.866718 · Cited by 111 · see citing works
mTOR Activity and Autophagy in Senescent Cells, a Complex Partnership
Cayo, Á., Segovia, R., Venturini, W., Moore‐Carrasco, R., Valenzuela, C. A., & Brown, N. E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158149 · Cited by 92 · see citing works
“Underlying senescence phenotypes, including the SASP, are complex changes in cellular metabolism [54,55].”
Background
An expanding GSK3 network: implications for aging research
Souder, D. C., & Anderson, R. M. (2019) · GeroScience · doi:10.1007/s11357-019-00085-z · Cited by 86 · see citing works
Senescent cells as promising targets to tackle age-related diseases
Prašnikar, E., Borišek, J., & Perdih, A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101251 · Cited by 74 · see citing works
The Emergence of Senescent Surface Biomarkers as Senotherapeutic Targets
Rossi, M. S., & Abdelmohsen, K. (2021) · Cells · doi:10.3390/cells10071740 · Cited by 73 · see citing works
Targeting tumor cell senescence and polyploidy as potential therapeutic strategies
Saleh, T., Carpenter, V. J., Bloukh, S., & Gewirtz, D. A. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.12.010 · Cited by 70 · see citing works
Aging of Liver in Its Different Diseases
Radonjić, T., Dukić, M., Jovanović, I., Zdravkovic, M. D., Mandić, O., Popadić, V., Popović, M., Nikolić, N., Klašnja, S., Divac, A., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113085 · Cited by 76 · see citing works
“Senescence represents the cell’s response to numerous stressors [20].”
BackgroundInfluential
Cell Senescence, Multiple Organelle Dysfunction and Atherosclerosis
Machado-Oliveira, G., Ramos, C., Marques, A. R. A., & Vieira, O. V. (2020) · Cells · doi:10.3390/cells9102146 · Cited by 66 · see citing works
“Although it is still not completely elucidated how these intracellular alterations in morphology and function take place and which regulatory pathways induce multiple organelle dysfunction, they are likely related, either by consequence or predisposal, to the defects in cellular metabolism detected during senescence […”
BackgroundInfluential
Targeting Mitochondrial Metabolism as a Strategy to Treat Senescence
Lee, Y. H., Park, J. Y., Lee, H., Song, E. S., Kuk, M. U., Joo, J., Oh, S., Kwon, H. W., Park, J. T., & Park, S. C. (2021) · Cells · doi:10.3390/cells10113003 · Cited by 66 · see citing works
Self-citation
Emerging Therapeutic Approaches to Target the Dark Side of Senescent Cells: New Hopes to Treat Aging as a Disease and to Delay Age-Related Pathologies
Khalil, R., Diab‐Assaf, M., & Lemaı̂tre, J.-M. (2023) · Cells · doi:10.3390/cells12060915 · Cited by 66 · see citing works
“Some pathways have been identified as being represented in different populations of senescent cells, such as inhibition of IMMP2L in RS or OIS [76], and ROS production appears to be not only a feature of senescent cells [60,77], but can also initiate a senescent phase on its own [74,75].”
Background
Satellite cell contribution to disease pathology in Duchenne muscular dystrophy
Kodippili, K., & Rudnicki, M. A. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1180980 · Cited by 61 · see citing works
“Senescent cells are metabolically active and secrete inflammatory cytokines and chemokines that lead to a further increase in chronic inflammation (Kwon et al., 2019).”
Background
The Emerging Role of Senescence in Ocular Disease
Sreekumar, P. G., Hinton, D. R., & Kannan, R. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/2583601 · Cited by 62 · see citing works
“Retrograde signaling is a mitochondrialto-nuclear signal transduction pathway by which defective mitochondria communicate with the nuclear genetic compartment [178, 179].”
Background
Cellular Senescence and Senotherapies in the Kidney: Current Evidence and Future Directions
Docherty, M. H., Baird, D., Hughes, J., & Ferenbach, D. A. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00755 · Cited by 63 · see citing works
Aging, Cancer, and Inflammation: The Telomerase Connection
Boccardi, V., & Marano, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158542 · Cited by 62 · see citing works
“Conversely, in cancer, where telomerase is often upregulated to support uncontrolled cell proliferation, telomerase inhibitors can be employed to limit tumor growth and enhance the effectiveness of existing treatments [34].”
BackgroundInfluential
Senescence-Induced Chemoresistance in Triple Negative Breast Cancer and Evolution-Based Treatment Strategies
Chakrabarty, A., Chakraborty, S., Bhattacharya, R., & Chowdhury, G. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.674354 · Cited by 56 · see citing works
Revisiting Glycogen in Cancer: A Conspicuous and Targetable Enabler of Malignant Transformation
Khan, T., Sullivan, M. A., Gunter, J. H., Kryza, T., Lyons, N., He, Y., & Hooper, J. D. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.592455 · Cited by 56 · see citing works
“Cell accumulation of glycogen granules is a hallmark of several physiological processes associated with senescence, including the replicative senescence of primary human fibroblasts and neuronal and hepatic aging (12, 44, 45).”
Background
Cellular senescence or stemness: hypoxia flips the coin
Otero-Albiol, D., & Carnero, A. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02035-0 · Cited by 53 · see citing works
MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Redox Control of Cell Senescence
Lettieri-Barbato, D., Aquilano, K., Punziano, C., Minopoli, G., & Faraonio, R. (2022) · Antioxidants · doi:10.3390/antiox11030480 · Cited by 51 · see citing works
“Despite their inability to replicate, senescent cells acquire specific features, such as morphological changes, metabolic and transcriptional reprogramming, as well as chromatin reorganization [27,60,61].”
Background
The role of metabolic checkpoint regulators in B cell survival and transformation
Jellusova, J. (2020) · Immunological Reviews · doi:10.1111/imr.12855 · Cited by 50 · see citing works
In Vitro Culture Expansion Shifts the Immune Phenotype of Human Adipose-Derived Mesenchymal Stem Cells
Jeske, R., Yuan, X., Fu, Q., Bunnell, B. A., Logan, T. M., & Li, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.621744 · Cited by 49 · see citing works
“Generally, extensive OXPHOS leads to the exhaustion of mitochondria and accumulation of ROS, which can account for the replicative senescence (66, 67).”
Background
Exercise mitigates age-related metabolic diseases by improving mitochondrial dysfunction
Jia, D., Tian, Z., & Wang, R. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102087 · Cited by 47 · see citing works
In Vitro Characterization of Doxorubicin-Mediated Stress-Induced Premature Senescence in Human Chondrocytes
Kirsch, V., Ramge, J.-M., Schoppa, A., Ignatius, A., & Riegger, J. (2022) · Cells · doi:10.3390/cells11071106 · Cited by 47 · see citing works
“It has been suggested that an increased size and number of lysosomes leads to a higher granularity in snCs, though the reason for this process has not been completely understood yet [36,37].”
Background
Inhibition of glutaminolysis restores mitochondrial function in senescent stem cells
Choudhury, D., Rong, N., Ikhapoh, I. A., Rajabian, N., Tseropoulos, G., Wu, Y., Mehrotra, P., Thiyagarajan, R., Shahini, A., Seldeen, K. L., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111744 · Cited by 44 · see citing works
Cellular Senescence in Health, Disease, and Lens Aging
Qin, Y., Liu, H., & Wu, H. (2025) · Pharmaceuticals · doi:10.3390/ph18020244 · Cited by 43 · see citing works
“Senescent cells exhibit altered glucose metabolism, increased glycolysis, and impaired oxidative phosphorylation [57].”
Meta-analysis of senescent cell secretomes to identify common and specific features of the different senescent phenotypes: a tool for developing new senotherapeutics
Oguma, Y., Alessio, N., Aprile, D., Dezawa, M., Peluso, G., Bernardo, G. D., & Galderisi, U. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01280-4 · Cited by 34 · see citing works
“Additionally, certain enzymes, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase M1/2 (PKM), and phosphoglycerate kinase 1 (PGK1), were consistently detected in the late stage [13, 28].”
Background
Senescent cells and SASP in cancer microenvironment: New approaches in cancer therapy
Özdemir, A., Demir, Y. D. Ş., Yeşilyurt, Z. E., & Ark, M. (2022) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2022.10.002 · Cited by 33 · see citing works
Branched‐Chain Amino Acid Accumulation Fuels the Senescence‐Associated Secretory Phenotype
Liang, Y., Pan, C. C., Yin, T., Wang, L., Gao, X., Wang, E., Quang, H., Huang, D., Tan, L., Xiang, K., et al. (2023) · Advanced Science · doi:10.1002/advs.202303489 · Cited by 31 · see citing works
Acid ceramidase promotes senescent cell survival
Munk, R. B., Anerillas, C., Rossi, M. S., Tsitsipatis, D., Martindale, J. L., Herman, A. B., Yang, J., Roberts, J. A., Varma, V. R., Pandey, P. R., et al. (2021) · Aging · doi:10.18632/aging.203170 · Cited by 30 · see citing works
“Although senescent cells do not divide, they remain metabolically active [5, 6]; this metabolic profile includes enhanced lysosomal activity associated with both growth arrest and a senescenceassociated secretory phenotype (SASP), whereby many proteins are secreted, including interleukin (IL) 6 and IL8 [7, 8].”
Background
GSK3β, a Master Kinase in the Regulation of Adult Stem Cell Behavior
Racaud‐Sultan, C., & Vergnolle, N. (2021) · Cells · doi:10.3390/cells10020225 · Cited by 27 · see citing works
“In addition to its role in survival of adult stem cells, active GSK3 prevents ROS‐induced differentiation or senescence [7].”
Background
Targeting mitochondria for ovarian aging: new insights into mechanisms and therapeutic potential
Wang, Z., Wang, Z.-J., Liu, H.-C., Wang, C.-Y., Wang, Y., Yang, Y., Zhao, C., Wang, G., & Wan, J. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1417007 · Cited by 26 · see citing works
“Therefore, adopting strategies to improve mitochondrial metabolism, enhance mitochondrial biogenesis, and limit ROS production is critical in preventing ovarian cell senescence and prolonging reproductive life (95).”
Method
Therapy-Induced Senescent/Polyploid Cancer Cells Undergo Atypical Divisions Associated with Altered Expression of Meiosis, Spermatogenesis and EMT Genes
Czarnecka‐Herok, J., Śliwińska, M. A., Herok, M., Targońska, A., Strzeszewska, A., Bojko, A., Wolny, A., Mosieniak, G., & Sikora, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158288 · Cited by 26 · see citing works
“The role of glycogen as a store of energy in the senescence process is not elucidated and requires further research [59].”
Background
Palbociclib treatment alters nucleotide biosynthesis and glutamine dependency in A549 cells
Conroy, L. R., Lorkiewicz, P. K., He, L., Yin, X., Zhang, X., Rai, S. N., & Clem, B. F. (2020) · Cancer Cell International · doi:10.1186/s12935-020-01357-x · Cited by 23 · see citing works
Differential effects of cisplatin combined with the flavonoid apigenin on HepG2, Hep3B, and Huh7 liver cancer cell lines
Papachristou, F., Αnninou, N., Koukoulis, G., Paraskakis, S., Sertaridou, E. N., Tsalikidis, C., Pitiakoudis, M., Simopoulos, C. E., & Tsaroucha, A. K. (2021) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2021.503352 · Cited by 23 · see citing works
Targeting Vascular Smooth Muscle Cell Senescence: A Novel Strategy for Vascular Diseases
Lin, M., Hu, S.-L., Tian, Y., Jing, Z., Liang, N., Sun, R., Gong, S.-X., & Wang, A. (2023) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-023-10377-7 · Cited by 23 · see citing works
“During senescence, misfolding of ribosomal, peroxisomal, and mitochondrial proteins occurs, leading to abnormal protein aggregation and cellular senescence can be accelerated [33].”
Background
Recent Advances in Strategies for Imaging Detection and Intervention of Cellular Senescence
Li, J., Bi, Z., Wang, L., Xia, Y., Xie, Y., & Liu, Y. (2022) · ChemBioChem · doi:10.1002/cbic.202200364 · Cited by 18 · see citing works
Iron Metabolism in Cancer and Senescence: A Cellular Perspective
Crescenzi, E., Leonardi, A., & Pacifico, F. (2023) · Biology · doi:10.3390/biology12070989 · Cited by 18 · see citing works
“In addition, mitochondrial alterations, such as an increase in mitochondrial mass, reduced oxidative phosphorylation and elevated ROS production, have been involved in cellular senescence [40].”
Background
Protein kinase CK2 activates Nrf2 via autophagic degradation of Keap1 and activation of AMPK in human cancer cells
Jang, D. E., Song, J., Park, J., Yoon, S.-H., & Bae, Y. (2020) · BMB Reports · doi:10.5483/bmbrep.2020.53.5.044 · Cited by 18 · see citing works
“tissues and species, and have been observed in various age-related diseases (3, 21-23), elucidating the molecular mechanism by which CK2 regulates the Keap1-Nrf2 axis will extend”
Background
The senotherapeutic potential of phytochemicals for age-related intestinal disease
Costa, C. M., Pedrosa, S. S., Kirkland, J. L., Reis, F., & Madureira, A. R. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102619 · Cited by 18 · see citing works
3-Deazaadenosine alleviates senescence to promote cellular fitness and cell therapy efficiency in mice
Guerrero, A., Innes, A. J., Roux, P., Buisman, S. C., Jung, J., Ortet, L., Moiseeva, V., Wagner, V., Robinson, L. J., Ausema, A., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00279-9 · Cited by 16 · see citing works
“An increase in glycogen aggregates had been observed in senescent cells and aged tissues 30 .”
Is Evidence Supporting the Subtelomere–Telomere Theory of Aging?
Libertini, G., Shubernetskaya, O., Corbi, G., & Ferrara, N. (2021) · Biochemistry (Moscow) · doi:10.1134/s0006297921120026 · Cited by 16 · see citing works
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Senoinflammation as the underlying mechanism of aging and its modulation by calorie restriction
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Hemistepsin A inhibits T0901317-induced lipogenesis in the liver
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Molecular changes in glaucomatous trabecular meshwork. Correlations with retinal ganglion cell death and novel strategies for neuroprotection
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Network Analysis of Demographics, Dietary Intake, and Comorbidity Interactions
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Molecular Radiation Biology
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Eimeria bovis Macromeront Formation Induces Glycolytic Responses and Mitochondrial Changes in Primary Host Endothelial Cells
Velásquez, Z. D., López-Osorio, S., Mazurek, S., Hermosilla, C. R., & Taubert, A. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.703413 · Cited by 8 · see citing works
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Upregulation and stabilization of senescence marker protein-30 by epigallocatechin gallate against tert-butyl hydroperoxide-induced liver injury in vitro and in vivo
Inoue, H., ARAKAWA, K., Tanaka, M., Katsumata-Tsuboi, R., Takahashi, N., & Uehara, M. (2020) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.20-119 · Cited by 7 · see citing works
Comprehensive investigations of key mitochondrial metabolic changes in senescent human fibroblasts
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Plasma and urine metabolomics for the identification of diagnostic biomarkers for sulfur mustard-induced lung injury
Jamshidi, V., Bagheri, H., Safari‐Alighiarloo, N., Salesi, M., Jamalkandi, S. A., Parvin, S., Ghanei, M., & Gh, B. F. N. M. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114515 · Cited by 5 · see citing works
Polynucleotides Enhance Collagen Synthesis via Modulating Phosphoenolpyruvate Carboxykinase 1 in Senescent Macrophages: Experimental Evidence
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The states of senescent cells
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Molecular mechanisms of cellular senescence
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Reduced Efficiency of DNA Repair and Antioxidant Defense Promotes the Accumulation of DNA Damage during Cell Senescence
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Pharmacologically targeting caveolae in metabolic diseases
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mTOR potentiates senescent phenotypes and primary cilia formation after cisplatin-induced G2 arrest in retinal pigment epithelial cells
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The role of senescence in cancer therapy-associated cardiovascular toxicity
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Additional file 1 of Meta-analysis of senescent cell secretomes to identify common and specific features of the different senescent phenotypes: a tool for developing new senotherapeutics
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Oguma, Y., Alessio, N., Aprile, D., Dezawa, M., Peluso, G., Bernardo, G. D., & Galderisi, U. (2024) · Figshare · doi:10.6084/m9.figshare.24217620
Additional file 3 of Meta-analysis of senescent cell secretomes to identify common and specific features of the different senescent phenotypes: a tool for developing new senotherapeutics
Oguma, Y., Alessio, N., Aprile, D., Dezawa, M., Peluso, G., Di Bernardo, G., & Galderisi, U. (2024) · Figshare · doi:10.6084/m9.figshare.26620513
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Authors: Kwon, S. M., Hong, S. M., Lee, Y.-K., Min, S., & Yoon, G.
Affiliations: Ajou University (KR)
ORCID: Kwon, So Mee
Hong, Sun Mi
Lee, Young-Kyoung
Min, Seongki
Yoon, Gyesoon
Venue: BMB Reports
Publisher: Korean Society for Biochemistry and Molecular Biology - BMB Reports
Published: 2019-01-31
Volume: 52
Issue: 1
Pages: 5-12
ISSN: 1976-6696 (ISSN-L)
1976-670X
DOI: 10.5483/bmbrep.2019.52.1.291
PMC: PMC6386228
OpenAlex: W2912150594
Cited by: 111
References: 96
Citations by year: 2026: 10 · 2025: 16 · 2024: 15 · 2023: 14 · 2022: 17 · 2021: 20 · 2020: 17 · 2019: 2
FWCI: 9.51
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc
Locations: BMB Reports (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
AJOU Open Repository (Ajou University) (submittedVersion, cc-by-nc)
Funders: National Research Foundation of Korea (2012R1A5A2048183)
Topics: Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords: cellular senescence, biological aging, metabolic regulation, mitochondrial dysfunction, mTOR, AMPK, glycogen synthase kinase-3, age-related diseases, metabolic syndrome
MeSH terms: Adenylate Kinase, Aging, Animals, Humans, Mitochondria, Phenotype, Signal Transduction, Cellular Senescence, Glycogen Synthase Kinase 3, TOR Serine-Threonine Kinases

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Metabolic features and regulation in cell senescence

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