B4195 - What makes clocks tick Mapping determinants of epigenetic age acceleration in early life - 15/11/2022

B number: 
Principal applicant name: 
Charlotte Cecil | Erasmus University Medical Center (the Netherlands)
Rosa Mulder, PhD, Dr Matthew Suderman
Title of project: 
What makes clocks tick? Mapping determinants of epigenetic age acceleration in early life
Proposal summary: 

DNA methylation, the binding of a methyl-group to the DNA structure, can affect gene transcription and is related to aging. So strongly, in fact, that DNA methylation at specific sites (i.e. ‘CpGs’) can be used to estimate a persons’ age through the use of so-called ‘epigenetic clocks’. Not only do the age estimates produced by epigenetic clocks relate highly to chronological age, but the extent to which they deviate from chronological age is an important predictor of health: in adults, epigenetic age acceleration (i.e. being epigenetically older than one’s age) relates to greater disease risk and mortality, whereas conversely, deceleration relates to better health and longevity.
Research from our group suggests that an individual’s epigenetic age acceleration might be determined early on. We brought together the world’s largest developmental datasets with repeated epigenetic assessments to map how DNA methylation patterns change over the first two decades of life. We found that sites that make up epigenetic clocks already show substantial differences between individuals in early life, sometimes even from birth. This raises the possibility that longevity differences apparent in old age may already be influenced by factors occurring at a young age, opening new opportunities for early detection and intervention.
Here, we aim to identify the early origins of epigenetic aging, by examining the contribution of genetic and environmental influences, beginning in pregnancy. To do so, we use individual-level DNA methylation patterns of change at clock CpGs, already created. In addition, we will study early outcomes of inter-individual variation in early epigenetic age acceleration at the molecular and system-level.

Impact of research: 
We think we can identify early genetic and environmental determinants of epigenetic age acceleration and identify early health outcomes. This research would help us understand the mechanism of biological aging and identify potential targets of intervention, to help people age healthily.
Date proposal received: 
Wednesday, 9 November, 2022
Date proposal approved: 
Friday, 11 November, 2022
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Allergy, Epilepsy, Hypertension, Infection, Learning difficulty, Mental health, Obesity, Pain, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Respiratory - asthma, Speech/language problem, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Developmental disorders - autism, Cancer, Chronic fatigue, Cognitive impairment, Diabetes, Eating disorders - anorexia, bulimia, Eczema, GWAS, Metabolomics, Microarrays, RNA, Ageing, Biological samples -e.g. blood, cell lines, saliva, etc., Genomics, Genome wide association study, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Childhood - childcare, childhood adversity, Development, Environment - enviromental exposure, pollution, Epigenetics, Expression, Genetic epidemiology