SIRT6 in Senescence and Aging-Related Cardiovascular Diseases

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2021 Apr 15

PMID 33855020

Citations 27

Authors

Xiaokang Li

Lin Liu

Tian Li

Manling Liu

Yishi Wang

Heng Ma

Nan Mu

Haiyan Wang

Affiliations

Soon will be listed here.

Abstract

SIRT6 belongs to the nicotinamide adenine dinucleotide (NAD)-dependent deacetylases and has established diverse roles in aging, metabolism and disease. Its function is similar to the , which prolongs lifespan and regulates genomic stability, telomere integrity, transcription, and DNA repair. It has been demonstrated that increasing the sirtuin level through genetic manipulation extends the lifespan of yeast, nematodes and flies. Deficiency of SIRT6 induces chronic inflammation, autophagy disorder and telomere instability. Also, these cellular processes can lead to the occurrence and progression of cardiovascular diseases (CVDs), such as atherosclerosis, hypertrophic cardiomyopathy and heart failure. Herein, we discuss the implications of SIRT6 regulates multiple cellular processes in cell senescence and aging-related CVDs, and we summarize clinical application of SIRT6 agonists and possible therapeutic interventions in aging-related CVDs.

Citing Articles

Genome-wide DNA methylation and transcriptome sequencing analyses of lens tissue in an age-related mouse cataract model.

Hu Y, Su D, Zhang Y, Fu Y, Li S, Chen X PLoS One. 2025; 20(1):e0316766.

PMID: 39883715 PMC: 11781636. DOI: 10.1371/journal.pone.0316766.

Antioxidant and longevity inducing properties of coconut water on human dermal fibroblasts.

Nakorn S, Dokduang H, Namwat N, Klanrit P, Wangwiwatsin A, Promraksa B Heliyon. 2025; 10(24):e41010.

PMID: 39759299 PMC: 11696670. DOI: 10.1016/j.heliyon.2024.e41010.

Drp1 Promotes Macrophage M1 Polarization and Inflammatory Response in Autoimmune Myocarditis by Driving Mitochondrial Fission.

Lin L, Wei J, Xue J, Fan G, Zhu W, Zhu Y J Cardiovasc Transl Res. 2024; .

PMID: 39388091 DOI: 10.1007/s12265-024-10570-2.

Efficacy of selective serotonin reuptake inhibitors-related antidepressants in Alzheimer's disease: a meta-analysis.

Wang H, Li S, Zhang J, Peng W, Li T, Zhang J Eur J Med Res. 2024; 29(1):438.

PMID: 39210432 PMC: 11360319. DOI: 10.1186/s40001-024-02006-z.

Meldonium, as a potential neuroprotective agent, promotes neuronal survival by protecting mitochondria in cerebral ischemia-reperfusion injury.

Yang W, Lei X, Liu F, Sui X, Yang Y, Xiao Z J Transl Med. 2024; 22(1):771.

PMID: 39148053 PMC: 11325598. DOI: 10.1186/s12967-024-05222-7.

References

Kenyon C . The genetics of ageing. Nature. 2010; 464(7288):504-12. DOI: 10.1038/nature08980. View

van der Pol A, van Gilst W, Voors A, van der Meer P . Treating oxidative stress in heart failure: past, present and future. Eur J Heart Fail. 2018; 21(4):425-435. PMC: 6607515. DOI: 10.1002/ejhf.1320. View

Kugel S, Mostoslavsky R . Chromatin and beyond: the multitasking roles for SIRT6. Trends Biochem Sci. 2014; 39(2):72-81. PMC: 3912268. DOI: 10.1016/j.tibs.2013.12.002. View

Ye J, Lenain C, Bauwens S, Rizzo A, Saint-Leger A, Poulet A . TRF2 and apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage. Cell. 2010; 142(2):230-42. DOI: 10.1016/j.cell.2010.05.032. View

Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L . The sirtuin SIRT6 regulates lifespan in male mice. Nature. 2012; 483(7388):218-21. DOI: 10.1038/nature10815. View

Childs B, Baker D, Wijshake T, Conover C, Campisi J, van Deursen J . Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science. 2016; 354(6311):472-477. PMC: 5112585. DOI: 10.1126/science.aaf6659. View

Csiszar A, Ungvari Z, Koller A, Edwards J, Kaley G . Aging-induced proinflammatory shift in cytokine expression profile in coronary arteries. FASEB J. 2003; 17(9):1183-5. DOI: 10.1096/fj.02-1049fje. View

Liu Z, Wang J, Huang X, Li Z, Liu P . Deletion of sirtuin 6 accelerates endothelial dysfunction and atherosclerosis in apolipoprotein E-deficient mice. Transl Res. 2016; 172:18-29.e2. DOI: 10.1016/j.trsl.2016.02.005. View

Madabhushi R, Pan L, Tsai L . DNA damage and its links to neurodegeneration. Neuron. 2014; 83(2):266-282. PMC: 5564444. DOI: 10.1016/j.neuron.2014.06.034. View

10.

Mitra S, Deshmukh A, Sachdeva R, Lu J, Mehta J . Oxidized low-density lipoprotein and atherosclerosis implications in antioxidant therapy. Am J Med Sci. 2011; 342(2):135-42. DOI: 10.1097/MAJ.0b013e318224a147. View

11.

Franceschi C, Campisi J . Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014; 69 Suppl 1:S4-9. DOI: 10.1093/gerona/glu057. View

12.

Pan H, Guan D, Liu X, Li J, Wang L, Wu J . SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2. Cell Res. 2016; 26(2):190-205. PMC: 4746611. DOI: 10.1038/cr.2016.4. View

13.

Nakamura S, Yoshimori T . Autophagy and Longevity. Mol Cells. 2018; 41(1):65-72. PMC: 5792715. DOI: 10.14348/molcells.2018.2333. View

14.

Robin J, Ludlow A, Batten K, Magdinier F, Stadler G, Wagner K . Telomere position effect: regulation of gene expression with progressive telomere shortening over long distances. Genes Dev. 2014; 28(22):2464-76. PMC: 4233240. DOI: 10.1101/gad.251041.114. View

15.

STARY H . Natural history and histological classification of atherosclerotic lesions: an update. Arterioscler Thromb Vasc Biol. 2000; 20(5):1177-8. DOI: 10.1161/01.atv.20.5.1177. View

16.

Niedernhofer L, Gurkar A, Wang Y, Vijg J, Hoeijmakers J, Robbins P . Nuclear Genomic Instability and Aging. Annu Rev Biochem. 2018; 87:295-322. DOI: 10.1146/annurev-biochem-062917-012239. View

17.

Huang Z, Zhao J, Deng W, Chen Y, Shang J, Song K . Identification of a cellularly active SIRT6 allosteric activator. Nat Chem Biol. 2018; 14(12):1118-1126. DOI: 10.1038/s41589-018-0150-0. View

18.

Bergeron N, P Phan B, Ding Y, Fong A, Krauss R . Proprotein convertase subtilisin/kexin type 9 inhibition: a new therapeutic mechanism for reducing cardiovascular disease risk. Circulation. 2015; 132(17):1648-66. DOI: 10.1161/CIRCULATIONAHA.115.016080. View

19.

Csiszar A, Labinskyy N, Podlutsky A, Kaminski P, Wolin M, Zhang C . Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations. Am J Physiol Heart Circ Physiol. 2008; 294(6):H2721-35. PMC: 2551743. DOI: 10.1152/ajpheart.00235.2008. View

20.

De Bont R, Van Larebeke N . Endogenous DNA damage in humans: a review of quantitative data. Mutagenesis. 2004; 19(3):169-85. DOI: 10.1093/mutage/geh025. View