Methylomic predictors demonstrate the role of NF-kappa B in old-age mortality and are unrelated to the aging-associated epigenetic drift
Jylhävä, Juulia; Kananen, Laura; Raitanen, Jani; Marttila, Saara; Nevalainen, Tapio; Hervonen, Antti; Jylhä, Marja; Hurme, Mikko (2016)
Jylhävä, Juulia
Kananen, Laura
Raitanen, Jani
Marttila, Saara
Nevalainen, Tapio
Hervonen, Antti
Jylhä, Marja
Hurme, Mikko
2016
Oncotarget 7 15
19228-19241
Lääketieteen yksikkö - School of Medicine
Terveystieteiden yksikkö - School of Health Sciences
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:uta-201606151917
https://urn.fi/URN:NBN:fi:uta-201606151917
Tiivistelmä
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.
Kokoelmat
- Artikkelit [6140]