Change in Epigenome-Wide DNA Methylation Over 9 Years and Subsequent Mortality: Results From the InCHIANTI Study.
Patterns of DNA methylation (DNAm) that track with aging have been identified. However, the relevance of these patterns for aging outcomes remains unclear. Longitudinal epigenome-wide DNAm information was obtained from the InCHIANTI study, a large representative European population. DNAm was evaluated using the Illumina HumanMethylation450 array on blood samples collected at baseline and 9-year follow-up: observations from 499 participants with paired longitudinal blood sample and information on differential blood count were included in analyses. A total of 56,579 markers were significantly associated with age in cross-sectional analysis of DNAm at year 9, 31,252 markers were changed significantly over the 9-year follow-up, and 16,987 markers were both cross-sectionally associated with age and significantly changed over time. Rates of change at 76 markers and year 9 level of DNAm at 88 markers were identified as strongly associated with mortality in Cox proportional hazard models adjusted for age and relevant covariates (mean follow-up time 4.4 years). Less than 0.05% of markers associated with age or that changed over time were also associated with mortality after adjusting for chronological age. Although the influence of DNAm on health and longevity remains unclear, these findings confirm that aging is associated cross-sectionally and longitudinally with robust and consistent patterns of methylation change.
Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
Ann Zenobia
AZ
Moore
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
Dena G
DG
Hernandez
Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
Toshiko
T
Tanaka
Epidemiology and Public Health, University of Exeter Medical School, University of Exeter, UK.
Luke C
LC
Pilling
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
Mike A
MA
Nalls
Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy.
Stefania
S
Bandinelli
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
Andrew B
AB
Singleton
Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
Luigi
L
Ferrucci
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001772:Blood Cell Count; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D019175:DNA Methylation / Q000235:genetics*; D057890:Epigenomics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008136:Longevity; D008297:Male; D008875:Middle Aged; D009026:Mortality
D015415:Biomarkers
Chronological age; Epigenome-wide DNA methylation; Survival