Insufficient DNA methylation affects healthy aging and promotes age-related health problems

Liang Liu, Thomas Van Groen, Inga Kadish, Yuanyuan Li, Deli Wang, Smitha R. James, Adam R. Karpf, Trygve O. Tollefsbol

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


DNA methylation plays an integral role in development and aging through epigenetic regulation of genome function. DNA methyltransferase 1 (Dnmt1) is the most prevalent DNA methyltransferase that maintains genomic methylation stability. To further elucidate the function of Dnmt1 in aging and age-related diseases, we exploited the Dnmt1+/- mouse model to investigate how Dnmt1 haploinsufficiency impacts the aging process by assessing the changes of several major aging phenotypes. We confirmed that Dnmt1 haploinsufficiency indeed decreases DNA methylation as a result of reduced Dnmt1 expression. To assess the effect of Dnmt1 haploinsufficiency on general body composition, we performed dualenergy X-ray absorptiometry analysis and showed that reduced Dnmt1 activity decreased bone mineral density and body weight, but with no significant impact on mortality or body fat content. Using behavioral tests, we demonstrated that Dnmt1 haploinsufficiency impairs learning and memory functions in an age-dependent manner. Taken together, our findings point to the interesting likelihood that reduced genomic methylation activity adversely affects the healthy aging process without altering survival and mortality. Our studies demonstrated that cognitive functions of the central nervous system are modulated by Dnmt1 activity and genomic methylation, highlighting the significance of the original epigenetic hypothesis underlying memory coding and function.

Original languageEnglish (US)
Pages (from-to)349-360
Number of pages12
JournalClinical epigenetics
Issue number2
StatePublished - Aug 2011
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgments We would like to thank Tanja Guentert, Angela Fitzgerald, and Frank Feng for the excellent technical assistance. This work was supported by grants from the Evelyn F. McKnight Brain Institute (T.O.T.) as well as the UAB Center for Aging (L.L.), the UAB Diabetes Research and Training Program (L.L.), and the Glenn Foundation for Medical Research (T.O.T.). TvG was partially supported by P30 NS47466. Funding was also obtained from R01CA11674 (A.R.K.).


  • Cognition
  • DNA methylation
  • Dnmt1
  • Epigenetics
  • Healthy aging


Dive into the research topics of 'Insufficient DNA methylation affects healthy aging and promotes age-related health problems'. Together they form a unique fingerprint.

Cite this