Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment

Wang, T., Tsui, B., Kreisberg, J. F., Robertson, N. A., Gross, A. M., Yu, M. K., Carter, H., Brown-Borg, H. M., Adams, P. D. and Ideker, T. (2017) Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment. Genome Biology, 18, 57. (doi: 10.1186/s13059-017-1186-2) (PMID:28351423) (PMCID:PMC5371228)

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Abstract

Background: Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. Results: We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1df/df dwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls. Conclusions: This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers.

Item Type:Articles
Keywords:Aging, DNA methylation, epigenetic aging, epigenomics.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robertson, Mr Neil and Adams, Professor Peter
Authors: Wang, T., Tsui, B., Kreisberg, J. F., Robertson, N. A., Gross, A. M., Yu, M. K., Carter, H., Brown-Borg, H. M., Adams, P. D., and Ideker, T.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Genome Biology
Publisher:BioMed Central
ISSN:1474-760X
ISSN (Online):1465-6906
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Genome Biology 18:57
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
510441Epigenetics of Aging and Age-associated diseases : Epigenetic regulation of senescence and agingPeter AdamsNational Institute of Health (USA) (NIH(US))P01 AG031862RI CANCER SCIENCES