Abstract
Ageing is a phenomenon in which cells, tissues and organs undergo systemic pathological changes as individuals age, leading to the occurrence of ageing-related diseases and the end of life. It is associated with many phenotypes known as ageing characteristics, such as genomic instability, nutritional imbalance, mitochondrial dysfunction, cell senescence, stem cell depletion, and an altered microenvironment. The sirtuin family (SIRT), known as longevity proteins, is thought to delay ageing and prolong life, and mammals, including humans, have seven family members (SIRT1-7). SIRT4 has been studied less among the sirtuin family thus far, but it has been reported that it has important physiological functions in organisms, such as promoting DNA damage repair, participating in the energy metabolism of three substances, inhibiting inflammatory reactions and apoptosis, and regulating mitochondrial function. Recently, some studies have demonstrated the involvement of SIRT4 in age-related processes, but knowledge in this field is still scarce. Therefore, this review aims to analyse the relationship between SIRT4 and ageing characteristics as well as some age-related diseases (e.g., cardiovascular diseases, metabolic diseases, neurodegenerative diseases and cancer).
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Abedi-Gaballu F, Kamal Kazemi E, Salehzadeh SA et al (2022) Metabolic pathways in breast cancer reprograming: an insight to non-coding RNAs. Cells. https://doi.org/10.3390/cells11192973
Afzaal A, Rehman K, Kamal S et al (2022) Versatile role of sirtuins in metabolic disorders: from modulation of mitochondrial function to therapeutic interventions. J Biochem Mol Toxicol 36 (7):e23047. https://doi.org/10.1002/jbt.23047
Amirazodi M, Mehrabi A, Rajizadeh MA et al (2022) The effects of combined resveratrol and high intensity interval training on the hippocampus in aged male rats: an investigation into some signaling pathways related to mitochondria. Iran J Basic Med Sci 25 (2):254–262. https://doi.org/10.22038/ijbms.2022.57780.12853
Amorim JA, Coppotelli G, Rolo AP et al (2022) Mitochondrial and metabolic dysfunction in ageing and age-related diseases. Nat Rev Endocrinol 18 (4):243–258. https://doi.org/10.1038/s41574-021-00626-7
Anderson KA, Huynh FK, Fisher-Wellman K et al (2017) SIRT4 Is a lysine deacylase that controls leucine metabolism and insulin secretion. Cell Metab 25 (4):838–55.e15. https://doi.org/10.1016/j.cmet.2017.03.003
Asghar M, Odeh A, Fattahi AJ et al (2022) Mitochondrial biogenesis, telomere length and cellular senescence in Parkinson’s disease and Lewy body dementia. Sci Rep 12 (1):17578. https://doi.org/10.1038/s41598-022-22400-z
Bai Y, Yang J, Cui Y et al (2020) Research progress of Sirtuin4 in cancer. Front Oncol 10:562950. https://doi.org/10.3389/fonc.2020.562950
Baur J, Ungvari Z, Minor R, et al (2012) Are sirtuins viable targets for improving healthspan and lifespan? 11(6):443–61. https://doi.org/10.1038/nrd3738
Benavente CA, Schnell SA, Jacobson EL (2012) Effects of niacin restriction on sirtuin and PARP responses to photodamage in human skin. PLoS ONE 7 (7):e42276. https://doi.org/10.1371/journal.pone.0042276
Betsinger CN, Cristea IM (2019) Mitochondrial function, metabolic regulation, and human disease viewed through the prism of Sirtuin 4 (SIRT4) functions. J Proteome Res 18 (5):1929–1938. https://doi.org/10.1021/acs.jproteome.9b00086
Bian C, Ren H (2022) Sirtuin family and diabetic kidney disease. Front Endocrinol 13:901066. https://doi.org/10.3389/fendo.2022.901066
Bognoni L, Colombo EA, Priolo M et al (2021) Pregnancy in a patient with Rothmund-Thomson type 2 syndrome. Int J Gynaecol Obst 154 (1):181–182. https://doi.org/10.1002/ijgo.13667
Burden of diabetes and hyperglycaemia in adults in the Americas, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Diabetes Endocrinol 2022;10 (9):655–667. https://doi.org/10.1016/s2213-8587(22)00186-3
Castex J, Willmann D, Kanouni T et al (2017) Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4. Cell Death Disease 8 (2):e2631. https://doi.org/10.1038/cddis.2017.48
Chen Y, Wang H, Luo G et al (2014) SIRT4 inhibits cigarette smoke extracts-induced mononuclear cell adhesion to human pulmonary microvascular endothelial cells via regulating NF-κB activity. Toxicol Lett 226 (3):320–327. https://doi.org/10.1016/j.toxlet.2014.02.022
Chen Z, Lin J, Feng S et al (2019) SIRT4 inhibits the proliferation, migration, and invasion abilities of thyroid cancer cells by inhibiting glutamine metabolism. Onco Targets Ther 12:2397–2408. https://doi.org/10.2147/ott.S189536
Choubey D, Cytosolic DNA (2022) Sensor IFI16 proteins: potential molecular integrators of interactions among the aging hallmarks. Ageing Res Rev. https://doi.org/10.1016/j.arr.2022.101765
Choubey SK, Prabhu D, Nachiappan M et al (2017) Molecular modeling, dynamics studies and density functional theory approaches to identify potential inhibitors of SIRT4 protein from Homo sapiens : a novel target for the treatment of type 2 diabetes. J Biomol Struct Dyn 35 (15):3316–3329. https://doi.org/10.1080/07391102.2016.1254117
Covarrubias A, Perrone R, Grozio A et al (2021) NAD metabolism and its roles in cellular processes during ageing. Nat Rev Mol 22 (2):119–141. https://doi.org/10.1038/s41580-020-00313-x
Dai XY, Zhao Y, Ge J et al (2021) Lycopene attenuates di (2-ethylhexyl) phthalate-induced mitophagy in spleen by regulating the sirtuin3-mediated pathway. Food Funct 12 (10):4582–4590. https://doi.org/10.1039/d0fo03277h
Di Emidio G, Falone S, Artini PG et al (2021) Mitochondrial sirtuins in reproduction. Antioxidants. https://doi.org/10.3390/antiox10071047
do Amaral ME, Ueno M, Oliveira CA et al (2011) Reduced expression of SIRT1 is associated with diminished glucose-induced insulin secretion in islets from calorie-restricted rats. J Nutr Biochem 22(6):554–559. https://doi.org/10.1016/j.jnutbio.2010.04.010
Duan R, Fu Q, Sun Y et al (2022) Epigenetic clock: a promising biomarker and practical tool in aging. Ageing Res Rev 81:101743. https://doi.org/10.1016/j.arr.2022.101743
Evangelou K, Vasileiou PV, Papaspyropoulos A et al (2022) Cellular senescence and cardiovascular diseases: moving to the “heart” of the problem. Physiol Rev. https://doi.org/10.1152/physrev.00007.2022
Fernandez-Marcos PJ, Serrano M (2013) Sirt4: the glutamine gatekeeper. Cancer Cell 23 (4):427–428. https://doi.org/10.1016/j.ccr.2013.04.003
Fiorentino F, Mautone N, Menna M et al (2022) Sirtuin modulators: past, present, and future perspectives. Future Med Chem 14 (12):915–939. https://doi.org/10.4155/fmc-2022-0031
Francois A, Canella A, Marcho LM et al (2021) Protein acetylation in cardiac aging. J Mol Cell Cardiol 157:90–97. https://doi.org/10.1016/j.yjmcc.2021.04.007
Fu L, Dong Q, He J et al (2017) SIRT4 inhibits malignancy progression of NSCLCs, through mitochondrial dynamics mediated by the ERK-Drp1 pathway. Oncogene 36 (19):2724–2736. https://doi.org/10.1038/onc.2016.425
Grootaert MOJ, Bennett MR (2022) Sirtuins in atherosclerosis: guardians of healthspan and therapeutic targets. Nat Rev Cardiol 19 (10):668–683. https://doi.org/10.1038/s41569-022-00685-x
Guo J, Chiang WC (2022) Mitophagy in aging and longevity. IUBMB Life 74 (4):296–316. https://doi.org/10.1002/iub.2585
Guo L, Zhou SR, Wei XB et al (2016) Acetylation of mitochondrial trifunctional protein α-subunit enhances its stability to promote fatty acid oxidation and is decreased in nonalcoholic fatty liver disease. Mol Cell Biol 36 (20):2553–2567. https://doi.org/10.1128/mcb.00227-16
Habib SJ, Acebrón SP (2022) Wnt signalling in cell division: from mechanisms to tissue engineering. Trends Cell Biol. https://doi.org/10.1016/j.tcb.2022.05.006
Haigis MC, Mostoslavsky R, Haigis KM et al (2006) SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126 (5):941–954. https://doi.org/10.1016/j.cell.2006.06.057
Han Y, Zhou S, Coetzee S et al (2019) SIRT4 and its roles in energy and redox metabolism in health, disease and during exercise. Front Physiol 10:1006. https://doi.org/10.3389/fphys.2019.01006
He M, Chiang HH, Luo H et al (2020) An acetylation switch of the NLRP3 inflammasome regulates aging-associated chronic inflammation and insulin resistance. Cell Metab 31 (3):580–91.e5. https://doi.org/10.1016/j.cmet.2020.01.009
He L, Liu F, Li J (2021) Mitochondrial sirtuins and doxorubicin-induced cardiotoxicity. Cardiovasc Toxicol 21 (3):179–191. https://doi.org/10.1007/s12012-020-09626-x
He L, Wang J, Yang Y et al (2022a) SIRT4 suppresses doxorubicin-induced cardiotoxicity by regulating the AKT/mTOR/autophagy pathway. Toxicology. https://doi.org/10.1016/j.tox.2022.153119
He L, Wang J, Yang Y et al (2022b) Mitochondrial sirtuins in Parkinson’s disease. Neurochem Res 47 (6):1491–1502. https://doi.org/10.1007/s11064-022-03560-w
Hong X, Isern J, Campanario S et al (2022) Mitochondrial dynamics maintain muscle stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy. Cell Stem Cell 29 (9):1298–314.e10. https://doi.org/10.1016/j.stem.2022.07.009
Hu Y, Lin J, Lin Y et al (2019) Overexpression of SIRT4 inhibits the proliferation of gastric cancer cells through cell cycle arrest. Oncol Lett 17 (2):2171–2176. https://doi.org/10.3892/ol.2018.9877
Huang FY, Wong DK, Seto WK et al (2021) Tumor suppressive role of mitochondrial sirtuin 4 in induction of G2/M cell cycle arrest and apoptosis in hepatitis B virus-related hepatocellular carcinoma. Cell Death Discov 7 (1):88. https://doi.org/10.1038/s41420-021-00470-8
Huang H, Ouyang Q, Mei K et al (2022) Acetylation of SCFD1 regulates SNARE complex formation and autophagosome-lysosome fusion. Autophagy. https://doi.org/10.1080/15548627.2022.2064624
Jeong SM, Xiao C, Finley LW et al (2013) SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell 23 (4):450–463. https://doi.org/10.1016/j.ccr.2013.02.024
Ji Z, Liu GH, Qu J (2022) Mitochondrial sirtuins, metabolism, and aging. J Genet Genomics 49 (4):287–298. https://doi.org/10.1016/j.jgg.2021.11.005
Jiang W, Ouyang X, Ji Z et al (2023) The PIK3CA-E545K-SIRT4 signaling axis reduces radiosensitivity by promoting glutamine metabolism in cervical cancer. Cancer Lett 556:216064. https://doi.org/10.1016/j.canlet.2023.216064
Kapoor RR, Flanagan SE, Fulton P et al (2009) Hyperinsulinism-hyperammonaemia syndrome: novel mutations in the GLUD1 gene and genotype-phenotype correlations. Eur J Endocrinol 161 (5):731–735. https://doi.org/10.1530/eje-09-0615
Karaca M, Frigerio F, Maechler P (2011) From pancreatic islets to central nervous system, the importance of glutamate dehydrogenase for the control of energy homeostasis. Neurochem Int 59 (4):510–517. https://doi.org/10.1016/j.neuint.2011.03.024
Kida Y, Goligorsky MS (2016) Sirtuins, cell senescence, and vascular aging. Can J Cardiol 32 (5):634–641. https://doi.org/10.1016/j.cjca.2015.11.022
Kofman AE, Huszar JM, Payne CJ (2013) Transcriptional analysis of histone deacetylase family members reveal similarities between differentiating and aging spermatogonial stem cells. Stem Cell Rev Rep 9 (1):59–64. https://doi.org/10.1007/s12015-012-9392-5
Kumar S, Lombard DB (2017) For certain, SIRT4 activities! Trends Biochem Sci 42 (7):499–501. https://doi.org/10.1016/j.tibs.2017.05.008
Lai Y, Li Z, Lu Z et al (2022) Roles of DNA damage repair and precise targeted therapy in renal cancer (Review). Oncol Rep. https://doi.org/10.3892/or.2022.8428
Lamis A, Siddiqui SW, Ashok T et al (2022) Hutchinson-gilford progeria syndrome: a literature review. Cureus 14 (8):e28629. https://doi.org/10.7759/cureus.28629
Lang A, Piekorz RP (2017) Novel role of the SIRT4-OPA1 axis in mitochondrial quality control. Cell Stress 2 (1):1–3. https://doi.org/10.15698/cst2018.01.118
Lang A, Grether-Beck S, Singh M et al (2016) MicroRNA-15b regulates mitochondrial ROS production and the senescence-associated secretory phenotype through sirtuin 4/SIRT4. Aging 8 (3):484–505. https://doi.org/10.18632/aging.100905
Lang A, Anand R, Altinoluk-Hambüchen S et al (2018) Correction: SIRT4 interacts with OPA1 and regulates mitochondrial quality control and mitophagy. Aging 10 (9):2536c. https://doi.org/10.18632/aging.101570
Langeh U, Kumar V, Kumar A et al (2022) Cellular and mitochondrial quality control mechanisms in maintaining homeostasis in aging. Rejuvenation Res 25 (5):208–222. https://doi.org/10.1089/rej.2022.0027
Laurent G, German NJ, Saha AK et al (2013a) SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol Cell 50 (5):686–698. https://doi.org/10.1016/j.molcel.2013.05.012
Laurent G, de Boer VC, Finley LW et al (2013b) SIRT4 represses peroxisome proliferator-activated receptor α activity to suppress hepatic fat oxidation. Mol Cell Biol 33 (22):4552–4561. https://doi.org/10.1128/mcb.00087-13
Lee Y, Shin MH, Kim MK et al (2021) Increased histone acetylation and decreased expression of specific histone deacetylases in ultraviolet-irradiated and intrinsically aged human skin in vivo. Int J Mol Sci. https://doi.org/10.3390/ijms22042032
Lei MZ, Li XX, Zhang Y et al (2020) Acetylation promotes BCAT2 degradation to suppress BCAA catabolism and pancreatic cancer growth. Signal Transduct Target Ther 5 (1):70. https://doi.org/10.1038/s41392-020-0168-0
Li T, Li Y, Liu T et al (2020) Mitochondrial PAK6 inhibits prostate cancer cell apoptosis via the PAK6-SIRT4-ANT2 complex. Theranostics 10(6):2571–2586. https://doi.org/10.7150/thno.42874
Li J, Zhan H, Ren Y et al (2022) Sirtuin 4 activates autophagy and inhibits tumorigenesis by upregulating the p53 signaling pathway. Cell Death Differ. https://doi.org/10.1038/s41418-022-01063-3
Lin YH, Major JL, Liebner T et al (2022) HDAC6 modulates myofibril stiffness and diastolic function of the heart. J Clin Investig. https://doi.org/10.1172/jci148333
Lingappa N, Mayrovitz HN (2022) Role of sirtuins in diabetes and age-related processes. Cureus 14 (9):e28774. https://doi.org/10.7759/cureus.28774
Liu X, Ouyang JF, Rossello FJ et al (2020) Reprogramming roadmap reveals route to human induced trophoblast stem cells. Nature 586 (7827):101–107. https://doi.org/10.1038/s41586-020-2734-6
Liu B, Qu J, Zhang W et al (2022) A stem cell aging framework, from mechanisms to interventions. Cell Rep 41 (3):111451. https://doi.org/10.1016/j.celrep.2022.111451
Luo YX, Tang X, An XZ et al (2017) SIRT4 accelerates Ang II-induced pathological cardiac hypertrophy by inhibiting manganese superoxide dismutase activity. Eur Heart J 38 (18):1389–1398. https://doi.org/10.1093/eurheartj/ehw138
Ma S, Sun S, Li J et al (2021) Single-cell transcriptomic atlas of primate cardiopulmonary aging. Cell Res 31 (4):415–432. https://doi.org/10.1038/s41422-020-00412-6
Maghbooli Z, Emamgholipour S, Aliakbar S et al (2020) Differential expressions of SIRT1, SIRT3, and SIRT4 in peripheral blood mononuclear cells from patients with type 2 diabetic retinopathy. Arch Physiol Biochem 126 (4):363–368. https://doi.org/10.1080/13813455.2018.1543328
Maguina M, Kang PB, Tsai AC et al (2022) Peripheral neuropathies associated with DNA repair disorders. Muscle Nerve. https://doi.org/10.1002/mus.27721
Mao L, Hong X, Xu L et al (2022) Sirtuin 4 inhibits prostate cancer progression and metastasis by modulating p21 nuclear translocation and glutamate dehydrogenase 1 ADP-ribosylation. J Oncol 2022:5498743. https://doi.org/10.1155/2022/5498743
Mathias RA, Greco TM, Oberstein A et al (2014) Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity. Cell 159(7):1615–1625. https://doi.org/10.1016/j.cell.2014.11.046
Min Z, Gao J, Yu Y (2018) The roles of mitochondrial SIRT4 in cellular metabolism. Front Endocrinol 9:783. https://doi.org/10.3389/fendo.2018.00783
Mohebi R, Chen C, Ibrahim NE et al (2022) Cardiovascular disease projections in the united states based on the 2020 census estimates. J Am Coll Cardiol 80 (6):565–578. https://doi.org/10.1016/j.jacc.2022.05.033
Musheev MU, Schomacher L, Basu A et al (2022) Mammalian N1-adenosine PARylation is a reversible DNA modification. Nat Commun 13 (1):6138. https://doi.org/10.1038/s41467-022-33731-w
Nacarelli T, Lau L, Fukumoto T et al (2019) NAD+ metabolism governs the proinflammatory senescence-associated secretome. Nat Cell Biol 21 (3):397–407. https://doi.org/10.1038/s41556-019-0287-4
Najumudeen AK, Ceteci F, Fey SK et al (2021) The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nat Genet 53 (1):16–26. https://doi.org/10.1038/s41588-020-00753-3
Navas LE, Carnero A (2021) NAD+ metabolism, stemness, the immune response, and cancer. Signal Transduct Target Ther 6 (1):2. https://doi.org/10.1038/s41392-020-00354-w
Okamoto N, Sato Y, Kawagoe Y et al (2022) Short-term resveratrol treatment restored the quality of oocytes in aging mice. Aging 14 (14):5628–5640. https://doi.org/10.18632/aging.204157
O’Neill L, Hardie DJN (2013) Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493 (7432):346–355. https://doi.org/10.1038/nature11862
Osborne B, Bentley NL, Montgomery MK et al (2016) The role of mitochondrial sirtuins in health and disease. Free Radical Biol Med 100:164–174. https://doi.org/10.1016/j.freeradbiomed.2016.04.197
Panyard DJ, Yu B, Snyder MP (2022) The metabolomics of human aging: advances, challenges, and opportunities. Sci Adv 8 (42):eadd6155. https://doi.org/10.1126/sciadv.add6155
Parik S, Tewary S, Ayyub C et al (2018) Loss of mitochondrial SIRT4 shortens lifespan and leads to a decline in physical activity. J Biosci 43 (2):243–247
Potthast AB, Heuer T, Warneke SJ et al (2017) Alterations of sirtuins in mitochondrial cytochrome c-oxidase deficiency. PLoS ONE 12 (10):e0186517. https://doi.org/10.1371/journal.pone.0186517
Ramatchandirin B, Sadasivam M, Kannan A et al (2016) Sirtuin 4 regulates lipopolysaccharide mediated leydig cell dysfunction. J Cell Biochem 117 (4):904–916. https://doi.org/10.1002/jcb.25374
Sarkar A, Dutta S, Sur M et al (2022) Early loss of endogenous NAD+ following rotenone treatment leads to mitochondrial dysfunction and Sarm1 induction that is ameliorated by PARP inhibition. FEBS J. https://doi.org/10.1111/febs.16652
Shaw E, Talwadekar M, Rashida Z et al (2020) Anabolic SIRT4 exerts retrograde control over TORC1 signaling by glutamine sparing in the mitochondria. Mol Cell Biol. https://doi.org/10.1128/mcb.00212-19
Shi Q, Liu T, Zhang X et al (2016) Decreased sirtuin 4 expression is associated with poor prognosis in patients with invasive breast cancer. Oncol Lett 12 (4):2606–2612. https://doi.org/10.3892/ol.2016.5021
Shi JX, Wang QJ, Li H et al (2017) SIRT4 overexpression protects against diabetic nephropathy by inhibiting podocyte apoptosis. Exp Ther Med 13 (1):342–348. https://doi.org/10.3892/etm.2016.3938
Shook BA, Wasko RR, Mano O et al (2020) Dermal adipocyte lipolysis and myofibroblast conversion are required for efficient skin repair. Cell Stem Cell 26 (6):880–95.e6. https://doi.org/10.1016/j.stem.2020.03.013
Son J, Lyssiotis CA, Ying H et al (2013) Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 496 (7443):101–105. https://doi.org/10.1038/nature12040
Soria-Valles C, Osorio FG, Gutiérrez-Fernández A et al (2015) NF-κB activation impairs somatic cell reprogramming in ageing. Nat Cell Biol 17 (8):1004–1013. https://doi.org/10.1038/ncb3207
Su S, Ndiaye M, Singh CK et al (2020) Mitochondrial sirtuins in skin and skin cancers. Photochem Photobiol 96 (5):973–980. https://doi.org/10.1111/php.13254
Takeda Y, Harada Y, Yoshikawa T et al (2023) Mitochondrial energy metabolism in the regulation of thermogenic brown fats and human metabolic diseases. Int J Mol Sci. https://doi.org/10.3390/ijms24021352
Tang X, Chen XF, Chen HZ et al (2017) Mitochondrial sirtuins in cardiometabolic diseases. Clin Sci 131 (16):2063–2078. https://doi.org/10.1042/cs20160685
Tao Y, Yu S, Chao M et al (2019) SIRT4 suppresses the PI3K/Akt/NF-κB signaling pathway and attenuates HUVEC injury induced by oxLDL. Mol Med Rep 19 (6):4973–4979. https://doi.org/10.3892/mmr.2019.10161
Tarantino G, Finelli C, Scopacasa F et al (2014) Circulating levels of sirtuin 4, a potential marker of oxidative metabolism, related to coronary artery disease in obese patients suffering from NAFLD, with normal or slightly increased liver enzymes. Oxidat Med Cell Long. https://doi.org/10.1155/2014/920676
Tomaselli D, Steegborn C, Mai A et al (2020) Sirt4: a multifaceted enzyme at the crossroads of mitochondrial metabolism and cancer. Front Oncol 10:474. https://doi.org/10.3389/fonc.2020.00474
Tomtheelnganbee E, Sah P, Sharma R (2022) Mitochondrial function and nutrient sensing pathways in ageing: enhancing longevity through dietary interventions. Biogerontology. https://doi.org/10.1007/s10522-022-09978-7
Trigo D, Vitória JJ, da Cruz E (2023) Novel therapeutic strategies targeting mitochondria as a gateway in neurodegeneration. Neural Regener Res 18 (5):991–995. https://doi.org/10.4103/1673-5374.355750
Tsai PI, Korotkevich E, O’Farrell PH (2022) Mitigation of age-dependent accumulation of defective mitochondrial genomes. Proc Natl Acad Sci USA 119 (31):e2119009119. https://doi.org/10.1073/pnas.2119009119
Walker JR, Zhu XD (2022) Role of Cockayne Syndrome Group B protein in replication stress: implications for cancer therapy. Int J Mol Sci. https://doi.org/10.3390/ijms231810212
Wan W, Hua F, Fang P et al (2022) Regulation of mitophagy by sirtuin family proteins: a vital role in aging and age-related diseases. Front Aging Neurosci 14:845330. https://doi.org/10.3389/fnagi.2022.845330
Wang S, Hu S (2022) The role of sirtuins in osteogenic differentiation of vascular smooth muscle cells and vascular calcification. Front Cardiovasc Med 9:894692. https://doi.org/10.3389/fcvm.2022.894692
Wang M, Lin HJ (2021) Understanding the Function of Mammalian Sirtuins and Protein Lysine Acylation 90:245–285. https://doi.org/10.1146/annurev-biochem-082520-125411
Wang CH, Wei YH (2020) Roles of mitochondrial sirtuins in mitochondrial function, redox homeostasis, insulin resistance and type 2 diabetes. Int J Mol Sci. https://doi.org/10.3390/ijms21155266
Wang HF, Li Q, Feng RL, et al (2012) Transcription levels of sirtuin family in neural stem cells and brain tissues of adult mice. Cell Mol Biol Suppl.58:Ol1737–43.
Wang C, Piao C, Liu J et al (2020) Mammalian SIRT4 is a tumor suppressor of clear cell renal cell carcinoma by inhibiting cancer proliferation, migration and invasion. Cancer Biomark 29 (4):453–462. https://doi.org/10.3233/cbm-191253
Wang T, Hu J, Li Y et al (2022a) Bloom syndrome helicase compresses single-stranded DNA into phase-separated condensates. Angew Chem 61 (39):e202209463. https://doi.org/10.1002/anie.202209463
Wang Y, Yue J, Xiao M et al (2022b) SIRT4-catalyzed deacetylation of Axin1 modulates the Wnt/β-catenin signaling pathway. Front Oncol 12:872444. https://doi.org/10.3389/fonc.2022.872444
Wasserzug-Pash P, Rothman R, Reich E et al (2022) Loss of heterochromatin and retrotransposon silencing as determinants in oocyte aging. Aging Cell 21 (3):e13568. https://doi.org/10.1111/acel.13568
Wong W, Crane ED, Zhang H et al (2022) Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging. Mol Metab 65:101575. https://doi.org/10.1016/j.molmet.2022.101575
Wood JG, Schwer B, Wickremesinghe PC et al (2018) Sirt4 is a mitochondrial regulator of metabolism and lifespan in Drosophila melanogaster. Proc Natl Acad Sci USA 115 (7):1564–1569. https://doi.org/10.1073/pnas.1720673115
Wu T, Liu YH, Fu YC et al (2014) Direct evidence of sirtuin downregulation in the liver of non-alcoholic fatty liver disease patients. Ann Clin Lab Sci 44 (4):410–418
Xia XH, Xiao CJ, Shan H (2017) Facilitation of liver cancer SMCC7721 cell aging by sirtuin 4 via inhibiting JAK2/STAT3 signal pathway. Eur Rev Med Pharmacol Sci 21 (6):1248–1253
Xiao Y, Zhang X, Fan S et al (2016) MicroRNA-497 inhibits cardiac hypertrophy by targeting Sirt4. PLoS ONE 11 (12):e0168078. https://doi.org/10.1371/journal.pone.0168078
Xing X, Zhang J, Zhang J et al (2022) Coenzyme Q10 supplement rescues postovulatory oocyte aging by regulating SIRT4 expression. Curr Mol Pharmacol 15 (1):190–203. https://doi.org/10.2174/1874467214666210420112819
Xu X, Zhang L, Hua F et al (2021) FOXM1-activated SIRT4 inhibits NF-κB signaling and NLRP3 inflammasome to alleviate kidney injury and podocyte pyroptosis in diabetic nephropathy. Exper Cell Res 408 (2):112863. https://doi.org/10.1016/j.yexcr.2021.112863
Yalçın GD, Colak M (2020) SIRT4 prevents excitotoxicity via modulating glutamate metabolism in glioma cells. Hum Exp Toxicol 39 (7):938–947. https://doi.org/10.1177/0960327120907142
Yang H, Yang T, Baur JA et al (2007) Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell 130 (6):1095–1107. https://doi.org/10.1016/j.cell.2007.07.035
Yang S, Xu W, Liu C et al (2022) LATS1 K751 acetylation blocks activation of Hippo signalling and switches LATS1 from a tumor suppressor to an oncoprotein. Sci China Life Sci 65(1):129–141. https://doi.org/10.1007/s11427-020-1914-3
Zaganjor E, Yoon H, Spinelli JB et al (2021) SIRT4 is an early regulator of branched-chain amino acid catabolism that promotes adipogenesis. Cell Rep 36(2):109345. https://doi.org/10.1016/j.celrep.2021.109345
Zeng J, Jiang M, Wu X et al (2018a) SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation. Aging Cell 17 (4):e12789. https://doi.org/10.1111/acel.12789
Zeng G, Liu H, Wang H (2018b) Amelioration of myocardial ischemia-reperfusion injury by SIRT4 involves mitochondrial protection and reduced apoptosis. Biochem Biophys Res Commun 502 (1):15–21. https://doi.org/10.1016/j.bbrc.2018.05.113
Zeng Z, Xu P, He Y et al (2022) Acetylation of Atp5f1c mediates cardiomyocyte senescence via metabolic dysfunction in radiation-induced heart damage. Oxidat Med Cell Long. https://doi.org/10.1155/2022/4155565
Zhang FW, Li D, Su J, Liu S, Lei QY et al (2022) Deacetylation of MTHFD2 by SIRT4 senses stress signal to inhibit cancer cell growth by remodeling folate metabolism. J Mol Cell Biol. https://doi.org/10.1093/jmcb/mjac020
Zullo A, Guida R, Sciarrillo R et al (2022) Redox homeostasis in cardiovascular disease: the role of mitochondrial sirtuins. Front Endocrinol 13:858330. https://doi.org/10.3389/fendo.2022.858330
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This review was supported by the National Natural Science Foundation of China (82160030) and Natural Science Foundation of Jiangxi Province (20224BAB216014).
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All authors involved in the conception and design of the study. Ling He, Qingcheng Liu and Jielong Chen prepared the manuscript. Mei Cao , Shuaimei Zhangand Xiaolin Wan draw pattern together. Jian LI and huaijun Tu oversaw the project and proofread the manuscript. All authors critically revised the paper and approved it for submission.
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He, L., Liu, Q., Cheng, J. et al. SIRT4 in ageing. Biogerontology 24, 347–362 (2023). https://doi.org/10.1007/s10522-023-10022-5
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DOI: https://doi.org/10.1007/s10522-023-10022-5