title: Methylomic predictors demonstrate the role of NF-κB in old-age mortality and are unrelated to the aging-associated epigenetic drift.
abstract: Changes in the DNA methylation (DNAm) landscape have been implicated in aging and cellular senescence. To unravel the role of specific DNAm patterns in late-life survival, we performed genome-wide methylation profiling in nonagenarians (n=111) and determined the performance of the methylomic predictors and conventional risk markers in a longitudinal setting. The survival model containing only the methylomic markers was superior in terms of predictive accuracy compared with the model containing only the conventional predictors or the model containing conventional predictors combined with the methylomic markers. At the 2.55-year follow-up, we identified 19 mortality-associated (false-discovery rate <0.5) CpG sites that mapped to genes functionally clustering around the nuclear factor kappa B (NF-κB) complex. Interestingly, none of the mortality-associated CpG sites overlapped with the established aging-associated DNAm sites. Our results are in line with previous findings on the role of NF-κB in controlling animal life spans and demonstrate the role of this complex in human longevity.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland.|Gerontology Research Center, University of Tampere, Tampere, Finland.
authors.forename: Juulia
authors.initials: J
authors.lastname: Jylhävä
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland.|Gerontology Research Center, University of Tampere, Tampere, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Kananen
authors.affiliation: School of Health Sciences, University of Tampere, Tampere, Finland.|UKK Institute for Health Promotion Research, Tampere, Finland.
authors.forename: Jani
authors.initials: J
authors.lastname: Raitanen
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland.|Gerontology Research Center, University of Tampere, Tampere, Finland.
authors.forename: Saara
authors.initials: S
authors.lastname: Marttila
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland.|Gerontology Research Center, University of Tampere, Tampere, Finland.
authors.forename: Tapio
authors.initials: T
authors.lastname: Nevalainen
authors.affiliation: Gerontology Research Center, University of Tampere, Tampere, Finland.|School of Health Sciences, University of Tampere, Tampere, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Hervonen
authors.affiliation: Gerontology Research Center, University of Tampere, Tampere, Finland.|School of Health Sciences, University of Tampere, Tampere, Finland.
authors.forename: Marja
authors.initials: M
authors.lastname: Jylhä
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland.|Gerontology Research Center, University of Tampere, Tampere, Finland.|Fimlab Laboratories, Tampere, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks; D040961:Genetic Drift; D006801:Humans; D008136:Longevity / Q000235:genetics; D008297:Male; D008957:Models, Genetic; D016328:NF-kappa B / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D016328:NF-kappa B
keywords: Cox model; Gerotarget; aging; longevity; methylation; mortality