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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Review Article

The Role of Resveratrol in Aging and Senescence: A Focus on Molecular Mechanisms

Author(s): Zeynab Kohandel, Majid Darrudi, Kobra Naseri, Fariborz Samini, Michael Aschner, Ali Mohammad Pourbagher-Shahri and Saeed Samarghandian*

Volume 24, Issue 7, 2024

Published on: 28 August, 2023

Page: [867 - 875] Pages: 9

DOI: 10.2174/1566524023666230602162949

Price: $65

Abstract

Resveratrol (Res), a polyphenol found in red wine, has been shown to decelerate aging, the progressive loss of physiological integrity and cellular senescence, characterized by the inability to progress through the cell cycle. No successful clinical trials have yet to be completed in humans on dose limitations. Yet, the potent anti-aging and anti-senescence efficacy of Res has been documented in several in vivo animal models. In this review, we highlight the molecular mechanisms of Res efficacy in antiaging disorders, such as diabetes, neurodegenerative disorders, eye diseases, and cardiovascular diseases.

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[1]
Di Micco R, Krizhanovsky V, Baker D, d’Adda di Fagagna F. Cellular senescence in ageing: From mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol 2021; 22(2): 75-95.
[http://dx.doi.org/10.1038/s41580-020-00314-w] [PMID: 33328614]
[2]
Schmeer C, Kretz A, Wengerodt D, Stojiljkovic M, Witte OW. Dissecting aging and senescence-current concepts and open lessons. Cells 2019; 8(11): 1446.
[http://dx.doi.org/10.3390/cells8111446] [PMID: 31731770]
[3]
McHugh D, Gil J. Senescence and aging: Causes, consequences, and therapeutic avenues. J Cell Biol 2018; 217(1): 65-77.
[http://dx.doi.org/10.1083/jcb.201708092] [PMID: 29114066]
[4]
Hoenicke L, Zender L. Immune surveillance of senescent cells-biological significance in cancer- and non-cancer pathologies. Carcinogenesis 2012; 33(6): 1123-6.
[http://dx.doi.org/10.1093/carcin/bgs124] [PMID: 22470164]
[5]
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013; 153(6): 1194-217.
[http://dx.doi.org/10.1016/j.cell.2013.05.039] [PMID: 23746838]
[6]
Campisi J, d’Adda di Fagagna F. Cellular senescence: When bad things happen to good cells. Nat Rev Mol Cell Biol 2007; 8(9): 729-40.
[http://dx.doi.org/10.1038/nrm2233] [PMID: 17667954]
[7]
Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol 2013; 75(1): 685-705.
[http://dx.doi.org/10.1146/annurev-physiol-030212-183653] [PMID: 23140366]
[8]
Campisi J, Andersen JK, Kapahi P, Melov S. Cellular senescence: A link between cancer and age-related degenerative disease? Semin Cancer Biol 2011; 21(6): 354-9.
[http://dx.doi.org/10.1016/j.semcancer.2011.09.001] [PMID: 21925603]
[9]
Rodier F, Campisi J. Four faces of cellular senescence. J Cell Biol 2011; 192(4): 547-56.
[http://dx.doi.org/10.1083/jcb.201009094] [PMID: 21321098]
[10]
Acosta JC, O’Loghlen A, Banito A, et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 2008; 133(6): 1006-18.
[http://dx.doi.org/10.1016/j.cell.2008.03.038] [PMID: 18555777]
[11]
Burton DGA, Krizhanovsky V. Physiological and pathological consequences of cellular senescence. Cell Mol Life Sci 2014; 71(22): 4373-86.
[http://dx.doi.org/10.1007/s00018-014-1691-3] [PMID: 25080110]
[12]
Campisi J. Cellular senescence as a tumor-suppressor mechanism. Trends Cell Biol 2001; 11(11): S27-31.
[http://dx.doi.org/10.1016/S0962-8924(01)02151-1] [PMID: 11684439]
[13]
Dimri GP. What has senescence got to do with cancer? Cancer Cell 2005; 7(6): 505-12.
[http://dx.doi.org/10.1016/j.ccr.2005.05.025] [PMID: 15950900]
[14]
Gewirtz DA, Holt SE, Elmore LW. Accelerated senescence: An emerging role in tumor cell response to chemotherapy and radiation. Biochem Pharmacol 2008; 76(8): 947-57.
[http://dx.doi.org/10.1016/j.bcp.2008.06.024] [PMID: 18657518]
[15]
Ewald JA, Desotelle JA, Wilding G, Jarrard DF. Therapy-induced senescence in cancer. J Natl Cancer Inst 2010; 102(20): 1536-46.
[http://dx.doi.org/10.1093/jnci/djq364] [PMID: 20858887]
[16]
Schmitt CA, Fridman JS, Yang M, et al. A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 2002; 109(3): 335-46.
[http://dx.doi.org/10.1016/S0092-8674(02)00734-1] [PMID: 12015983]
[17]
Amiri F, Zarnani AH, Zand H, Koohdani F, Jeddi-Tehrani M, Vafa M. Synergistic anti-proliferative effect of resveratrol and etoposide on human hepatocellular and colon cancer cell lines. Eur J Pharmacol 2013; 718(1-3): 34-40.
[http://dx.doi.org/10.1016/j.ejphar.2013.09.020] [PMID: 24055188]
[18]
Gao Z, Xu MS, Barnett TL, Xu CW. Resveratrol induces cellular senescence with attenuated mono-ubiquitination of histone H2B in glioma cells. Biochem Biophys Res Commun 2011; 407(2): 271-6.
[http://dx.doi.org/10.1016/j.bbrc.2011.02.008] [PMID: 21481687]
[19]
Samarghandian S, Azimi-Nezhad M, Mehrad-Majd H, Mirhafez SR. Thymoquinone ameliorates acute renal failure in gentamicin-treated adult male rats. Pharmacology 2015; 96(3-4): 112-7.
[http://dx.doi.org/10.1159/000436975] [PMID: 26202209]
[20]
Harikumar KB, Aggarwal BB. Resveratrol: A multitargeted agent for age-associated chronic diseases. Cell Cycle 2008; 7(8): 1020-35.
[http://dx.doi.org/10.4161/cc.7.8.5740] [PMID: 18414053]
[21]
Ghorbani A, Zand H, Jeddi-Tehrani M, Koohdani F, Shidfar F, Keshavarz SA. PTEN over-expression by resveratrol in acute lymphoblastic leukemia cells along with suppression of AKT/PKB and ERK1/2 in genotoxic stress. J Nat Med 2015; 69(4): 507-12.
[http://dx.doi.org/10.1007/s11418-015-0915-7] [PMID: 25929783]
[22]
Saiko P, Szakmary A, Jaeger W, Szekeres T. Resveratrol and its analogs: Defense against cancer, coronary disease and neurodegenerative maladies or just a fad? Mutat Res Rev Mutat Res 2008; 658(1-2): 68-94.
[http://dx.doi.org/10.1016/j.mrrev.2007.08.004] [PMID: 17890139]
[23]
Li B, Hou D, Guo H, et al. Resveratrol sequentially induces replication and oxidative stresses to drive p53-CXCR2 mediated cellular senescence in cancer cells. Sci Rep 2017; 7(1): 208.
[http://dx.doi.org/10.1038/s41598-017-00315-4] [PMID: 28303009]
[24]
Bishayee A, Dhir N. Resveratrol-mediated chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis: Inhibition of cell proliferation and induction of apoptosis. Chem Biol Interact 2009; 179(2-3): 131-44.
[http://dx.doi.org/10.1016/j.cbi.2008.11.015] [PMID: 19073162]
[25]
Athar M, Back J, Tang X, et al. Resveratrol: A review of preclinical studies for human cancer prevention. Toxicol Appl Pharmacol 2007; 224(3): 274-83.
[http://dx.doi.org/10.1016/j.taap.2006.12.025] [PMID: 17306316]
[26]
Wang W, Li P, Xu J, et al. Resveratrol attenuates high glucose-induced nucleus pulposus cell apoptosis and senescence through activating the ROS-mediated PI3K/Akt pathway. Biosci Rep 2018; 38(2): BSR20171454.
[http://dx.doi.org/10.1042/BSR20171454] [PMID: 29273676]
[27]
Tang Y, Xu J, Qu W, et al. Resveratrol reduces vascular cell senescence through attenuation of oxidative stress by SIRT1/NADPH oxidase-dependent mechanisms. J Nutr Biochem 2012; 23(11): 1410-6.
[http://dx.doi.org/10.1016/j.jnutbio.2011.08.008] [PMID: 22284404]
[28]
Zhang E, Guo Q, Gao H, Xu R, Teng S, Wu Y. Metformin and resveratrol inhibited high glucose-induced metabolic memory of endothelial senescence through SIRT1/p300/p53/p21 pathway. PLoS One 2015; 10(12): e0143814.
[http://dx.doi.org/10.1371/journal.pone.0143814] [PMID: 26629991]
[29]
Yang Q, Wang B, Zang W, et al. Resveratrol inhibits the growth of gastric cancer by inducing G1 phase arrest and senescence in a Sirt1-dependent manner. PLoS One 2013; 8(11): e70627.
[http://dx.doi.org/10.1371/journal.pone.0070627] [PMID: 24278101]
[30]
Luo H, Yang A, Schulte BA, Wargovich MJ, Wang GY. Resveratrol induces premature senescence in lung cancer cells via ROS-mediated DNA damage. PLoS One 2013; 8(3): e60065.
[http://dx.doi.org/10.1371/journal.pone.0060065] [PMID: 23533664]
[31]
Howitz KT, Bitterman KJ, Cohen HY, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003; 425(6954): 191-6.
[http://dx.doi.org/10.1038/nature01960] [PMID: 12939617]
[32]
Wood JG, Rogina B, Lavu S, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 2004; 430(7000): 686-9.
[http://dx.doi.org/10.1038/nature02789] [PMID: 15254550]
[33]
Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 2006; 16(3): 296-300.
[http://dx.doi.org/10.1016/j.cub.2005.12.038] [PMID: 16461283]
[34]
Kilic Eren M, Kilincli A, Eren Ö. Resveratrol induced premature senescence is associated with DNA damage mediated SIRT1 and SIRT2 down-regulation. PLoS One 2015; 10(4): e0124837.
[http://dx.doi.org/10.1371/journal.pone.0124837] [PMID: 25924011]
[35]
Li T, Peng F, Reiter RJ, Yang Y. Editorial: SIRT family in endocrinology. Front Endocrinol 2019; 10: 347.
[http://dx.doi.org/10.3389/fendo.2019.00347] [PMID: 31214121]
[36]
Vassilopoulos A, Fritz KS, Petersen DR, Gius D. The human sirtuin family: Evolutionary divergences and functions. Hum Genomics 2011; 5(5): 485-96.
[http://dx.doi.org/10.1186/1479-7364-5-5-485] [PMID: 21807603]
[37]
Giovannelli L, Pitozzi V, Jacomelli M, et al. Protective effects of resveratrol against senescence-associated changes in cultured human fibroblasts. J Gerontol A Biol Sci Med Sci 2011; 66A(1): 9-18.
[http://dx.doi.org/10.1093/gerona/glq161] [PMID: 20884849]
[38]
Zang M, Xu S, Maitland-Toolan KA, et al. Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice. Diabetes 2006; 55(8): 2180-91.
[http://dx.doi.org/10.2337/db05-1188] [PMID: 16873680]
[39]
Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006; 444(7117): 337-42.
[http://dx.doi.org/10.1038/nature05354] [PMID: 17086191]
[40]
Reinisalo M, Kårlund A, Koskela A, Kaarniranta K, Karjalainen RO. Polyphenol stilbenes: Molecular mechanisms of defence against oxidative stress and aging-related diseases. Oxid Med Cell Longev 2015; 2015: 1-24.
[http://dx.doi.org/10.1155/2015/340520] [PMID: 26180583]
[41]
Taguchi K, Fujikawa N, Komatsu M, et al. Keap1 degradation by autophagy for the maintenance of redox homeostasis. Proc Natl Acad Sci USA 2012; 109(34): 13561-6.
[http://dx.doi.org/10.1073/pnas.1121572109] [PMID: 22872865]
[42]
Liu X, Peyton KJ, Shebib AR, Wang H, Korthuis RJ, Durante W. Activation of AMPK stimulates heme oxygenase-1 gene expression and human endothelial cell survival. Am J Physiol Heart Circ Physiol 2011; 300(1): H84-93.
[http://dx.doi.org/10.1152/ajpheart.00749.2010] [PMID: 21037234]
[43]
Kornicka K, Szłapka-Kosarzewska J, Śmieszek A, Marycz K. 5-Azacytydine and resveratrol reverse senescence and ageing of adipose stem cells via modulation of mitochondrial dynamics and autophagy. J Cell Mol Med 2019; 23(1): 237-59.
[http://dx.doi.org/10.1111/jcmm.13914] [PMID: 30370650]
[44]
Matos L, Gouveia AM, Almeida H. Resveratrol attenuates copper-induced senescence by improving cellular proteostasis. Oxid Med Cell Longev 2017; 2017: 1-12.
[http://dx.doi.org/10.1155/2017/3793817] [PMID: 28280523]
[45]
Siemann EH, Creasy LL. Concentration of the phytoalexin resveratrol in wine. Am J Enol Vitic 1992; 43(1): 49-52.
[http://dx.doi.org/10.5344/ajev.1992.43.1.49]
[46]
Hattori R, Otani H, Maulik N, Das DK. Pharmacological preconditioning with resveratrol: Role of nitric oxide. Am J Physiol Heart Circ Physiol 2002; 282(6): H1988-95.
[http://dx.doi.org/10.1152/ajpheart.01012.2001] [PMID: 12003802]
[47]
Farkhondeh T, Llorens S, Pourbagher-Shahri AM, et al. An overview of the role of adipokines in cardiometabolic diseases. Molecules 2020; 25(21): 5218.
[http://dx.doi.org/10.3390/molecules25215218 ] [PMID: 33182462]
[48]
Bonnefont-Rousselot D. Resveratrol and cardiovascular diseases. Nutrients 2016; 8(5): 250.
[http://dx.doi.org/10.3390/nu8050250] [PMID: 27144581]
[49]
Dehghani A, Hafizibarjin Z, Najjari R, Kaseb F, Safari F. Resveratrol and 1,25-dihydroxyvitamin D co-administration protects the heart against d-galactose-induced aging in rats: Evaluation of serum and cardiac levels of klotho. Aging Clin Exp Res 2019; 31(9): 1195-205.
[http://dx.doi.org/10.1007/s40520-018-1075-x] [PMID: 30484255]
[50]
Shaterzadeh-Yazdi H, Noorbakhsh MF, Hayati F, Samarghandian S, Farkhondeh T. Immunomodulatory and anti-inflammatory effects of thymoquinone. Cardiovascular & Haematological Disorders-Drug Targets (Formerly Current Drug Targets-Cardiovascular & Hematological Disorders) 2018; 18(1): 52-60.
[http://dx.doi.org/10.1016/j.intimp.2015.06.023] [PMID: 26117430]
[51]
Börzsei D, Sebestyén J, Szabó R, et al. Resveratrol as a promising polyphenol in age-associated cardiac alterations. Oxid Med Cell Longev 2022; 2022: 1-8.
[http://dx.doi.org/10.1155/2022/7911222] [PMID: 35761875]
[52]
Chu SH, Yang D, Wang Y, Yang R, Qu L, Zeng H. Effect of resveratrol on the repair of kidney and brain injuries and its regulation on klotho gene in d-galactose-induced aging mice. Bioorg Med Chem Lett 2021; 40: 127913.
[http://dx.doi.org/10.1016/j.bmcl.2021.127913] [PMID: 33705905]
[53]
Sovrani V, Bobermin LD, Santos CL, et al. Effects of long-term resveratrol treatment in hypothalamic astrocyte cultures from aged rats. Mol Cell Biochem 2022; 2022: 8638714.
[http://dx.doi.org/10.1007/s11010-022-04585-z] [PMID: 36272012]
[54]
Amirazodi M, Daryanoosh F, Mehrabi A, et al. Interactive effects of swimming high-intensity interval training and resveratrol supplementation improve mitochondrial protein levels in the hippocampus of aged rats. BioMed Res Int 2022; 2022: 1-10.
[http://dx.doi.org/10.1155/2022/8638714] [PMID: 36536955]
[55]
Uddin MJ, Farjana M, Moni A, Hossain KS, Hannan MA, Ha H. Prospective pharmacological potential of resveratrol in delaying kidney aging. Int J Mol Sci 2021; 22(15): 8258.
[http://dx.doi.org/10.3390/ijms22158258] [PMID: 34361023]
[56]
Kim EN, Lim JH, Kim MY, et al. Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury. Aging (Albany NY) 2018; 10(1): 83-99.
[http://dx.doi.org/10.18632/aging.101361] [PMID: 29326403]
[57]
Abharzanjani F, Hemmati M. Protective effects of Quercetin and Resveratrol on aging markers in kidney under high glucose condition: In vivo and in vitro analysis. Mol Biol Rep 2021; 48(7): 5435-42.
[http://dx.doi.org/10.1007/s11033-021-06550-3] [PMID: 34273031]
[58]
Jang IA, Kim E, Lim J, et al. Effects of resveratrol on the renin-angiotensin system in the aging kidney. Nutrients 2018; 10(11): 1741.
[http://dx.doi.org/10.3390/nu10111741] [PMID: 30424556]
[59]
Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: Burdens upon an aging, changing nation. J Clin Oncol 2009; 27(17): 2758-65.
[http://dx.doi.org/10.1200/JCO.2008.20.8983] [PMID: 19403886]
[60]
Faget DV, Ren Q, Stewart SA. Unmasking senescence: Context-dependent effects of SASP in cancer. Nat Rev Cancer 2019; 19(8): 439-53.
[http://dx.doi.org/10.1038/s41568-019-0156-2] [PMID: 31235879]
[61]
Samarghandian S, Azimi-Nezhad M, Samini F. Preventive effect of safranal against oxidative damage in aged male rat brain. Experimental Animals 2015; 64(1): 65-71.
[http://dx.doi.org/10.1538/expanim.14-0027] [PMID: 25312506]
[62]
Wang L, Ebrahimi KB, Chyn M, Cano M, Handa JT. Biology of p62/sequestosome-1 in Age-Related Macular Degeneration (AMD). Adv Exp Med Biol 2016; 854: 17-22.
[http://dx.doi.org/10.1007/978-3-319-17121-0_3]
[63]
Kelly GS. A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: Part 2. Altern Med Rev 2010; 15(4): 313-28.
[64]
Kolosova NG, Kozhevnikova OS, Telegina DV, et al. p62/SQSTM1 coding plasmid prevents age related macular degeneration in a rat model. Aging 2018; 10(8): 2136-47.
[http://dx.doi.org/10.18632/aging.101537] [PMID: 30153656]
[65]
Oyenihi OR, Oyenihi AB, Adeyanju AA, Oguntibeju OO. Antidiabetic effects of resveratrol: The way forward in its clinical utility. J Diabetes Res 2016; 2016: 1-14.
[http://dx.doi.org/10.1155/2016/9737483] [PMID: 28050570]
[66]
Scrocchi LA, Drucker DJ. Effects of aging and a high fat diet on body weight and glucose tolerance in glucagon-like peptide-1 receptor -/- mice. Endocrinology 1998; 139(7): 3127-32.
[http://dx.doi.org/10.1210/endo.139.7.6092] [PMID: 9645685]
[67]
Thadhani VM. Resveratrol in management of diabetes and obesity: Clinical applications, bioavailability, and nanotherapyResveratrol. United Kingdom: IntechOpen 2019.
[http://dx.doi.org/10.5772/intechopen.79498]
[68]
Jeyaraman MM, Al-Yousif NSH, Singh Mann A, et al. Resveratrol for adults with type 2 diabetes mellitus. Cochrane Libr 2020; 2020(1): CD011919.
[http://dx.doi.org/10.1002/14651858.CD011919.pub2] [PMID: 31978258]

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