title: DNA damage markers in dermal fibroblasts in vitro reflect chronological donor age.
abstract: The aging process is accompanied by an accumulation of cellular damage, which compromises the viability and function of cells and tissues. We aim to further explore the association between in vitro DNA damage markers and the chronological age of the donor, as well as long-lived family membership and presence of cardiovascular diseases. Therefore, numbers of 53BP1 foci, telomere-associated foci (TAF) and micronuclei were measured in cultured dermal fibroblasts obtained from three age groups of donors (mean age 22, 63 and 90 years). Fibroblasts were cultured without a stressor and with 0.6 μM rotenone for 3 days. We found that 53BP1 foci and TAF were more frequently present in fibroblasts of old donors compared to middle-aged and young donors. No association between micronuclei and donor age was found. Within the fibroblasts of the middle-aged donors we did not find associations between DNA damage markers and long-lived family membership or cardiovascular disease. Results were comparable when fibroblasts were stressed in vitro with rotenone. In conclusion, we found that DNA damage foci of cultured fibroblasts are significantly associated with the chronological age, but not biological age, of the donor.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors.forename: Mariëtte E C
authors.initials: ME
authors.lastname: Waaijer
authors.affiliation: Department for Life Quality Studies, University of Bologna, 40126 Bologna, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Croco
authors.affiliation: Department of Public Health and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, 1123 Copenhagen, Denmark.
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.|Netherlands Consortium for Healthy Aging, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02903, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Sedivy
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Lorenzini
authors.affiliation: Department of Internal Medicine, Section of Gerontology and Geriatrics, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.|Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville VIC 3050, Australia.
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Maier
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D016922:Cellular Senescence; D004249:DNA Damage; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D012402:Rotenone / Q000494:pharmacology; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014015:Tissue Banks; D000071857:Tumor Suppressor p53-Binding Protein 1 / Q000378:metabolism; D055815:Young Adult
chemical_list: C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D012402:Rotenone
keywords: 53BP1; biological age; human aging; micronuclei; telomere-associated foci
references.citation: J Am Geriatr Soc. 2002 Aug;50(8):1405-10
references.pmid: 12164998
references.citation: Mutat Res. 2001 Nov 15;498(1-2):159-67
references.pmid: 11673081
references.citation: Nat Cell Biol. 2004 Feb;6(2):168-70
references.pmid: 14755273
references.citation: Mutat Res. 1985 Jan-Feb;148(1-2):99-105
references.pmid: 3918259
references.citation: Mech Ageing Dev. 1987 Jul;39(2):113-9
references.pmid: 3626636
references.citation: Mutat Res. 1991 Jul;263(3):173-7
references.pmid: 2067557
references.citation: Ann N Y Acad Sci. 1992 Nov 21;663:4-16
references.pmid: 1282788
references.citation: Cancer Epidemiol Biomarkers Prev. 1997 Apr;6(4):249-56
references.pmid: 9107430
references.citation: Mutat Res. 1999 Apr 6;425(2):225-30
references.pmid: 10216215
references.citation: Eur J Hum Genet. 2006 Jan;14(1):79-84
references.pmid: 16251894
references.citation: Science. 2006 Mar 3;311(5765):1257
references.pmid: 16456035
references.citation: Mech Ageing Dev. 2007 Jan;128(1):36-44
references.pmid: 17116315
references.citation: Aging Cell. 2007 Feb;6(1):27-33
references.pmid: 17266674
references.citation: Aging Cell. 2008 Jan;7(1):89-100
references.pmid: 18005250
references.citation: Ageing Res Rev. 2009 Jul;8(3):237-43
references.pmid: 19491042
references.citation: Aging Cell. 2009 Jun;8(3):311-23
references.pmid: 19627270
references.citation: Aging Cell. 2009 Sep;8(5):595-603
references.pmid: 19681808
references.citation: N Engl J Med. 2009 Oct 8;361(15):1475-85
references.pmid: 19812404
references.citation: J Am Geriatr Soc. 2009 Sep;57(9):1634-7
references.pmid: 19682117
references.citation: Mutat Res. 2010 Jul-Sep;705(1):60-7
references.pmid: 20307686
references.citation: BMC Cell Biol. 2010;11:34
references.pmid: 20492670
references.citation: J Mol Cell Cardiol. 2010 Oct;49(4):606-16
references.pmid: 20655924
references.citation: J Cell Biol. 2010 Sep 6;190(5):741-9
references.pmid: 20805320
references.citation: Methods Mol Biol. 2011;682:217-34
references.pmid: 21057931
references.citation: J Gerontol A Biol Sci Med Sci. 2011 Jan;66(1):45-50
references.pmid: 20937674
references.citation: Aging (Albany NY). 2011 Sep;3(9):836-45
references.pmid: 21931182
references.citation: Mutat Res. 2011 Nov-Dec;728(3):88-97
references.pmid: 21763453
references.citation: Nature. 2012 Feb 2;482(7383):53-8
references.pmid: 22258507
references.citation: Nat Commun. 2012;3:708
references.pmid: 22426229
references.citation: Nat Cell Biol. 2012 Apr;14(4):355-65
references.pmid: 22426077
references.citation: PLoS One. 2013;8(5):e63932
references.pmid: 23691119
references.citation: Cell. 2013 Jun 6;153(6):1194-217
references.pmid: 23746838
references.citation: Mutagenesis. 2014 May;29(3):215-9
references.pmid: 24618992
references.citation: Biogerontology. 2014 Jun;15(3):269-78
references.pmid: 24664125
references.citation: Mutat Res Genet Toxicol Environ Mutagen. 2015 Apr;782:30-5
references.pmid: 25868129
references.citation: J Invest Dermatol. 2015 Aug;135(8):1954-68
references.pmid: 25815425
references.citation: Environ Mol Mutagen. 2001;37(1):31-45
references.pmid: 11170240
references.citation: Radiat Environ Biophys. 2001 Mar;40(1):83-9
references.pmid: 11357715
references.citation: Nature. 2003 Nov 13;426(6963):194-8
references.pmid: 14608368