A pro-oxidant combination of resveratrol and copper down-regulates multiple biological hallmarks of ageing and neurodegeneration in mice.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
14 10 2022
14 10 2022
Historique:
received:
30
06
2022
accepted:
27
09
2022
entrez:
14
10
2022
pubmed:
15
10
2022
medline:
19
10
2022
Statut:
epublish
Résumé
Billions of cells die in the body every day, and cell-free chromatin particles (cfChPs) which are released from them enter into the extracellular compartments of the body, including into the circulation. cfChPs are known to readily enter into healthy cells to damage their DNA and activate apoptotic and inflammatory pathways. We have hypothesized that lifelong assault on healthy cells by cfChPs is the underlying cause of ageing, and that ageing could be retarded by deactivating extra-cellular cfChPs. The latter can be effected by oxygen radicals that are generated upon admixing the nutraceuticals resveratrol and copper (R-Cu). The present study investigated whether prolonged administration of R-Cu would retard biological hallmarks of ageing. C57Bl/6 mice were divided into 3 equal groups; one group was sacrificed at age 3 months, and which acted as young controls. The remaining mice were allowed to age, and at age 10 months the experimental ageing group was given R-Cu by oral gavage twice daily for further 12 months at a dose of 1 mg/kg of R and 0.1 μg/kg of Cu. The control ageing group was given water by oral gavage twice daily for 12 months. Animals of both groups were sacrificed at age 22 months. R-Cu treatment led to reduction of several biological hallmarks of ageing in brain cells which included telomere attrition, amyloid deposition, DNA damage, apoptosis, inflammation, senescence, aneuploidy and mitochondrial dysfunction. R-Cu treatment also led to significant reduction in blood levels of glucose, cholesterol and C-reactive protein. These findings suggest that cfChPs may act as global instigators of ageing and neurodegeneration, and that therapeutic use of R-Cu may help to make healthy ageing an attainable goal.
Identifiants
pubmed: 36241685
doi: 10.1038/s41598-022-21388-w
pii: 10.1038/s41598-022-21388-w
pmc: PMC9568542
doi:
Substances chimiques
Chromatin
0
Reactive Oxygen Species
0
Water
059QF0KO0R
Copper
789U1901C5
C-Reactive Protein
9007-41-4
Glucose
IY9XDZ35W2
Resveratrol
Q369O8926L
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
17209Informations de copyright
© 2022. The Author(s).
Références
EMBO J. 2002 Jul 1;21(13):3358-69
pubmed: 12093737
Nat Rev Cardiol. 2018 Sep;15(9):505-522
pubmed: 30065258
Cell Death Differ. 1999 Feb;6(2):99-104
pubmed: 10200555
Bioorg Med Chem. 2006 Mar 1;14(5):1437-43
pubmed: 16249091
Mech Ageing Dev. 2002 Feb;123(4):245-60
pubmed: 11744038
DNA Repair (Amst). 2019 Jan;73:110-119
pubmed: 30497961
Aging Dis. 2013 Mar 01;4(3):154-69
pubmed: 23730531
Br J Cancer. 2007 Mar 12;96(5):686-91
pubmed: 17311013
J Nutr Biochem. 2018 Sep;59:56-63
pubmed: 29960117
J Gerontol. 1956 Jul;11(3):298-300
pubmed: 13332224
Genes (Basel). 2019 May 28;10(6):
pubmed: 31142004
Methods Enzymol. 1990;186:1-85
pubmed: 2172697
FASEB J. 1988 Sep;2(12):2807-11
pubmed: 3044905
J Biosci. 2015 Mar;40(1):91-111
pubmed: 25740145
Cell Death Dis. 2018 Nov 15;9(12):1142
pubmed: 30442925
Aging Dis. 2010 Oct 1;1(2):72-74
pubmed: 21132086
Comp Med. 2006 Feb;56(1):17-22
pubmed: 16521855
Cell. 2013 Jun 6;153(6):1194-217
pubmed: 23746838
Ann N Y Acad Sci. 2011 Jan;1215:22-33
pubmed: 21261638
Nature. 2021 Apr;592(7856):695-703
pubmed: 33911272
Oxid Med Cell Longev. 2021 Jul 11;2021:9932218
pubmed: 34336123
Mol Cell. 2016 Sep 1;63(5):729-38
pubmed: 27588601
Nature. 2000 Nov 9;408(6809):239-47
pubmed: 11089981
Cancer Biother Radiopharm. 2002 Aug;17(4):405-26
pubmed: 12396705
Nat Aging. 2021;1(10):865
pubmed: 34518819
Clin Ther. 2005;27 Suppl B:S42-56
pubmed: 16519037
Nucleic Acids Res. 2002 May 15;30(10):e47
pubmed: 12000852
Adv Gerontol. 2014;27(1):72-80
pubmed: 25051761
Nutrition. 2016 Feb;32(2):174-8
pubmed: 26706021
Neurology. 2012 Feb 7;78(6):387-95
pubmed: 22302550
Ageing Res Rev. 2016 Aug;29:90-112
pubmed: 27353257
J Alzheimers Dis. 2010;19(1):311-23
pubmed: 20061647
Genes (Basel). 2021 Jan 26;12(2):
pubmed: 33530310
Diabetes Care. 2017 Apr;40(4):440-443
pubmed: 28325794
Cell. 2009 Aug 21;138(4):628-44
pubmed: 19703392
Molecules. 2020 Oct 12;25(20):
pubmed: 33053864
NPJ Aging Mech Dis. 2017 Sep 15;3:13
pubmed: 28944077
Mol Cell. 2016 Mar 3;61(5):654-666
pubmed: 26942670
Ann Oncol. 2017 Sep 01;28(9):2119-2127
pubmed: 28911066
Nat Med. 2021 Jan;27(1):45-48
pubmed: 33432173
Nature. 2006 Nov 16;444(7117):337-42
pubmed: 17086191
Cell Death Discov. 2017 May 29;3:17015
pubmed: 28580170
PLoS One. 2020 Mar 4;15(3):e0229017
pubmed: 32130239
Aging Cell. 2018 Oct;17(5):e12802
pubmed: 29963744
Annu Rev Genet. 2016 Nov 23;50:45-66
pubmed: 27893964
Front Immunol. 2021 Feb 01;12:622738
pubmed: 33597956
Clin Interv Aging. 2007;2(3):377-87
pubmed: 18044188
J Neurosci. 2010 Apr 14;30(15):5368-75
pubmed: 20392958
J Trace Elem Med Biol. 2016 May;35:107-15
pubmed: 27049134
Science. 2015 Dec 4;350(6265):1193-8
pubmed: 26785477
J Cell Sci. 2008 Dec 15;121(Pt 24):4018-28
pubmed: 19056671
Oxid Med Cell Longev. 2017;2017:8416763
pubmed: 28819546
J Biosci. 2012 Jun;37(2):301-12
pubmed: 22581336
Aging Dis. 2019 Apr 1;10(2):367-382
pubmed: 31011483
Science. 2015 Dec 4;350(6265):1191-3
pubmed: 26785476
F1000Res. 2015 Oct 27;4:1145
pubmed: 27134724
Nat Rev Mol Cell Biol. 2021 Feb;22(2):75-95
pubmed: 33328614
Bioorg Med Chem Lett. 1998 Nov 17;8(22):3187-92
pubmed: 9873700
J Cell Sci. 2011 Jan 1;124(Pt 1):68-81
pubmed: 21118958
Nature. 2016 Feb 11;530(7589):184-9
pubmed: 26840489
J Clin Exp Pathol. 2012 Jun 20;Suppl 4:
pubmed: 25300955
J Biol Chem. 1998 Mar 6;273(10):5858-68
pubmed: 9488723
Aging Dis. 2017 Oct 1;8(5):628-642
pubmed: 28966806
PLoS One. 2022 Feb 4;17(2):e0262212
pubmed: 35120140
Nature. 2018 Feb;554(7692):293-295
pubmed: 32094723