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2016 ; 7
(15
): 19228-41
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gab.com Text
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Methylomic predictors demonstrate the role of NF-?B in old-age mortality and are
unrelated to the aging-associated epigenetic drift
#MMPMID27015559
Jylhävä J
; Kananen L
; Raitanen J
; Marttila S
; Nevalainen T
; Hervonen A
; Jylhä M
; Hurme M
Oncotarget
2016[Apr]; 7
(15
): 19228-41
PMID27015559
show ga
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-?B) 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-?B in controlling animal
life spans and demonstrate the role of this complex in human longevity.