2018
DOI: 10.18632/aging.101508
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Abstract: DNA methylation (DNAm)-based biomarkers of aging have been developed for many tissues and organs. However, these biomarkers have sub-optimal accuracy in fibroblasts and other cell types used in ex vivo studies. To address this challenge, we developed a novel and highly robust DNAm age estimator (based on 391 CpGs) for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva samples. High age correlations can also be observed in sorted neurons, glia, brain… Show more

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Cited by 285 publications
(414 citation statements)
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References 46 publications
(64 reference statements)
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“…Epigenetic mechanisms act to regulate gene expression developmentally via chemical modifications to DNA and histone proteins (Bernstein et al, 2007), conferring cell-typespecific patterns of gene expression and differing markedly between tissues and celltypes (Mendizabal and Yi, 2016). There has been recent interest in the dynamic changes in epigenetic processes over the life course, and a number of 'epigenetic clocks' based on one specific epigenetic modification -DNA methylation (DNAm) -have been developed that appear to be highly predictive of chronological age (Campisi and Vijg, 2009;Horvath, 2013;Horvath et al, 2012Horvath et al, , 2018Knight et al, 2016;Oberdoerffer and Sinclair, 2007;Simpkin et al, 2017). The landmark DNAm clock was developed by Horvath (Horvath, 2013), who applied elastic net regression to Illumina DNAm array data from a large number of samples derived from a range of tissues (n = ~ 8,000…”
Section: Introductionmentioning
confidence: 99%
“…Epigenetic mechanisms act to regulate gene expression developmentally via chemical modifications to DNA and histone proteins (Bernstein et al, 2007), conferring cell-typespecific patterns of gene expression and differing markedly between tissues and celltypes (Mendizabal and Yi, 2016). There has been recent interest in the dynamic changes in epigenetic processes over the life course, and a number of 'epigenetic clocks' based on one specific epigenetic modification -DNA methylation (DNAm) -have been developed that appear to be highly predictive of chronological age (Campisi and Vijg, 2009;Horvath, 2013;Horvath et al, 2012Horvath et al, , 2018Knight et al, 2016;Oberdoerffer and Sinclair, 2007;Simpkin et al, 2017). The landmark DNAm clock was developed by Horvath (Horvath, 2013), who applied elastic net regression to Illumina DNAm array data from a large number of samples derived from a range of tissues (n = ~ 8,000…”
Section: Introductionmentioning
confidence: 99%
“…1a and e). Fibroblasts were derived from arm and abdomen skin biopsies (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) years for the young control, n=3, and 60-70 years for the aged group, n= 3), while endothelial cells were extracted from iliac vein and artery (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) years for the young control, n=3, and 45-50 years for the aged group, n=3). We utilized a non-integrative reprogramming protocol that we optimized, based on a cocktail of mRNAs expressing OCT4, SOX2, KLF4, c-MYC, LIN28 and NANOG (OSKMLN) 11 .…”
Section: Mainmentioning
confidence: 99%
“…Previously, we have demonstrated that chromosomes in proliferating primary HGPS cells are mislocalized and are located in nonrandom positions as if the cells were quiescent . Although, recent studies assessing the specific epigenetic clock DNA methylation markings of HGPS cells indicate that they have a prematurely aged signature . However, following treatment with farnesyl transferase inhibitors (FTIs), that prevent the farnesylation of proteins, leads to the mutant lamin A protein—progerin—to have no farnesylation moieties, and so does not become associated aberrantly with the nuclear envelope during mitosis, which restores chromosome territory to that of control cells …”
Section: Introductionmentioning
confidence: 99%
“…65 Although, recent studies assessing the specific epigenetic clock DNA methylation markings of HGPS cells indicate that they have a prematurely aged signature. 70 However, following treatment with farnesyl transferase inhibitors (FTIs), that prevent the farnesylation of proteins, leads to the mutant lamin A protein-progerin-to have no farnesylation moieties, and so does not become associated aberrantly with the nuclear envelope during mitosis, which restores chromosome territory to that of control cells. 66,71 In an effort to make HGPS cells more easily cultured and assayable, we employed cells that had been immortalized by hTERT.…”
Section: Introductionmentioning
confidence: 99%