A rat epigenetic clock recapitulates phenotypic aging and co-localizes with heterochromatin

Autor: Kathy A Perdue, Meng Wang, Christopher Dunn, Rafael de Cabo, Luigi Ferrucci, Ross A. McDevitt, Andrea Di Francesco, Kyra Thrush, Margarita Meer, Colin Farrell, Theresa Meade, Matteo Pellegrini, Morgan E. Levine
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Aging
Mouse
Inbred C57BL
Epigenesis
Genetic
Mice
computational biology
0302 clinical medicine
Biomarkers of aging
Heterochromatin
E2F1
rat
Biology (General)
Genetics
Inbred F344
DNA methylation
General Neuroscience
systems biology
General Medicine
Phenotype
030220 oncology & carcinogenesis
Reduced representation bisulfite sequencing
Medicine
caloric restriction
Research Article
Computational and Systems Biology
QH301-705.5
Science
1.1 Normal biological development and functioning
Genomics
Biology
Basic Behavioral and Social Science
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Genetic
Underpinning research
Biological Clocks
Behavioral and Social Science
genomics
Animals
Epigenetics
mouse
General Immunology and Microbiology
Human Genome
Genetics and Genomics
Rats
Inbred F344
Rats
biological age
Mice
Inbred C57BL
030104 developmental biology
Rat
Generic health relevance
Biochemistry and Cell Biology
Biomarkers
epigenetic clock
Epigenesis
Unsupervised Machine Learning
Zdroj: eLife
eLife, Vol 9 (2020)
ISSN: 2050-084X
Popis: Robust biomarkers of aging have been developed from DNA methylation in humans and more recently, in mice. This study aimed to generate a novel epigenetic clock in rats—a model with unique physical, physiological, and biochemical advantages—by incorporating behavioral data, unsupervised machine learning, and network analysis to identify epigenetic signals that not only track with age, but also relates to phenotypic aging. Reduced representation bisulfite sequencing (RRBS) data was used to train an epigenetic age (DNAmAge) measure in Fischer 344 CDF (F344) rats. This measure correlated with age at (r = 0.93) in an independent sample, and related to physical functioning (p=5.9e-3), after adjusting for age and cell counts. DNAmAge was also found to correlate with age in male C57BL/6 mice (r = 0.79), and was decreased in response to caloric restriction. Our signatures driven by CpGs in intergenic regions that showed substantial overlap with H3K9me3, H3K27me3, and E2F1 transcriptional factor binding.
Databáze: OpenAIRE
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