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Epigenetic age analysis of children who seem to evade aging.

ABSTRACT: We previously reported the unusual case of a teenage girl stricken with multifocal developmental dysfunctions whose physical development was dramatically delayed resulting in her appearing to be a toddler or at best a preschooler, even unto the occasion of her death at the age of 20 years. Her life-long physician felt that the disorder was unique in the world and that future treatments for age-related diseases might emerge from its study. The objectives of our research were to determine if other such cases exist, and if so, whether aging is actually slowed. Of seven children characterized by dramatically slow developmental rates, five also had associated disorders displayed by the first case. All of the identified subjects were female. To objectively measure the age of blood tissue from these subjects, we used a highly accurate biomarker of aging known as "epigenetic clock" based on DNA methylation levels. No statistically significant differences in chronological and epigenetic ages were detected in any of the newly discovered cases.

SUBMITTER: Walker RF

PROVIDER: S-EPMC4468314 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Epigenetic age analysis of children who seem to evade aging.

Walker Richard F RF Liu Jia Sophie JS Peters Brock A BA Ritz Beate R BR Wu Timothy T Ophoff Roel A RA Horvath Steve S

Aging 20150501 5

We previously reported the unusual case of a teenage girl stricken with multifocal developmental dysfunctions whose physical development was dramatically delayed resulting in her appearing to be a toddler or at best a preschooler, even unto the occasion of her death at the age of 20 years. Her life-long physician felt that the disorder was unique in the world and that future treatments for age-related diseases might emerge from its study. The objectives of our research were to determine if other ...[more]

PMID: 25991677

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Project description:BackgroundThe study of biological age acceleration may help identify at-risk individuals and reduce the rising global burden of age-related diseases. Using DNA methylation (DNAm) clocks, we investigated biological aging in schizophrenia (SCZ), a mental illness that is associated with an increased prevalence of age-related disabilities and morbidities. In a whole blood DNAm sample of 1090 SCZ cases and 1206 controls across four European cohorts, we performed a meta-analysis of differential aging using three DNAm clocks (i.e., Hannum, Horvath, and Levine). To dissect how DNAm aging contributes to SCZ, we integrated information on duration of illness and SCZ polygenic risk, as well as stratified our analyses by chronological age and biological sex.ResultsWe found that blood-based DNAm aging is significantly altered in SCZ independent from duration of the illness since onset. We observed sex-specific and nonlinear age effects that differed between clocks and point to possible distinct age windows of altered aging in SCZ. Most notably, intrinsic cellular age (Horvath clock) is decelerated in SCZ cases in young adulthood, while phenotypic age (Levine clock) is accelerated in later adulthood compared to controls. Accelerated phenotypic aging was most pronounced in women with SCZ carrying a high polygenic burden with an age acceleration of + 3.82 years (CI 2.02-5.61, P = 1.1E-03). Phenotypic aging and SCZ polygenic risk contributed additively to the illness and together explained up to 14.38% of the variance in disease status.ConclusionsOur study contributes to the growing body of evidence of altered DNAm aging in SCZ and points to intrinsic age deceleration in younger adulthood and phenotypic age acceleration in later adulthood in SCZ. Since increased phenotypic age is associated with increased risk of all-cause mortality, our findings indicate that specific and identifiable patient groups are at increased mortality risk as measured by the Levine clock. Our study did not find that DNAm aging could be explained by the duration of illness of patients, but we did observe age- and sex-specific effects that warrant further investigation. Finally, our results show that combining genetic and epigenetic predictors can improve predictions of disease outcomes and may help with disease management in schizophrenia.

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Epigenetic age analysis of children who seem to evade aging.

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Epigenetic age analysis of children who seem to evade aging.

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