title: Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment.
abstract: 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.
  
  
  
  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/dfdwarfism, 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.
  
  
  
  This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.|Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, 92093, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Tsui
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
authors.forename: Jason F
authors.initials: JF
authors.lastname: Kreisberg
authors.affiliation: Beatson Institute for Cancer Research and University of Glasgow, Glasgow, UK.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Robertson
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.|Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, 92093, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Gross
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.|Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, 92093, USA.
authors.forename: Michael Ku
authors.initials: MK
authors.lastname: Yu
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.|Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, 92093, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Carter
authors.affiliation: Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, 58202, USA.
authors.forename: Holly M
authors.initials: HM
authors.lastname: Brown-Borg
authors.affiliation: Beatson Institute for Cancer Research and University of Glasgow, Glasgow, UK.|Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Adams
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. tideker@ucsd.edu.
authors.forename: Trey
authors.initials: T
authors.lastname: Ideker
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D004392:Dwarfism / Q000235:genetics* / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D057890:Epigenomics / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008136:Longevity / Q000235:genetics; D008297:Male; D051379:Mice; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D020123:Sirolimus
keywords: Aging; DNA methylation; Epigenetic aging; Epigenomics