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 journalArticle

45 Citations (Scopus)

Abstract

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
Volume2
Issue number2
DOIs
StatePublished - Aug 1 2011

Fingerprint

Methyltransferases
DNA Methylation
DNA
Health
Haploinsufficiency
Methylation
Epigenomics
Mortality
Genomic Instability
Photon Absorptiometry
Body Composition
Bone Density
Cognition
Adipose Tissue
Central Nervous System
Body Weight
Learning
Genome
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

Cite this

Liu, L., Van Groen, T., Kadish, I., Li, Y., Wang, D., James, S. R., ... Tollefsbol, T. O. (2011). Insufficient DNA methylation affects healthy aging and promotes age-related health problems. Clinical Epigenetics, 2(2), 349-360. https://doi.org/10.1007/s13148-011-0042-6

Insufficient DNA methylation affects healthy aging and promotes age-related health problems. / Liu, Liang; Van Groen, Thomas; Kadish, Inga; Li, Yuanyuan; Wang, Deli; James, Smitha R.; Karpf, Adam R.; Tollefsbol, Trygve O.

In: Clinical Epigenetics, Vol. 2, No. 2, 01.08.2011, p. 349-360.

Research output: Contribution to journalArticle

Liu, L, Van Groen, T, Kadish, I, Li, Y, Wang, D, James, SR, Karpf, AR & Tollefsbol, TO 2011, 'Insufficient DNA methylation affects healthy aging and promotes age-related health problems', Clinical Epigenetics, vol. 2, no. 2, pp. 349-360. https://doi.org/10.1007/s13148-011-0042-6
Liu, Liang ; Van Groen, Thomas ; Kadish, Inga ; Li, Yuanyuan ; Wang, Deli ; James, Smitha R. ; Karpf, Adam R. ; Tollefsbol, Trygve O. / Insufficient DNA methylation affects healthy aging and promotes age-related health problems. In: Clinical Epigenetics. 2011 ; Vol. 2, No. 2. pp. 349-360.
@article{e7100a7fc4024506832dfc1c555919d1,
title = "Insufficient DNA methylation affects healthy aging and promotes age-related health problems",
abstract = "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.",
keywords = "Cognition, DNA methylation, Dnmt1, Epigenetics, Healthy aging",
author = "Liang Liu and {Van Groen}, Thomas and Inga Kadish and Yuanyuan Li and Deli Wang and James, {Smitha R.} and Karpf, {Adam R.} and Tollefsbol, {Trygve O.}",
year = "2011",
month = "8",
day = "1",
doi = "10.1007/s13148-011-0042-6",
language = "English (US)",
volume = "2",
pages = "349--360",
journal = "Clinical Epigenetics",
issn = "1868-7075",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - Insufficient DNA methylation affects healthy aging and promotes age-related health problems

AU - Liu, Liang

AU - Van Groen, Thomas

AU - Kadish, Inga

AU - Li, Yuanyuan

AU - Wang, Deli

AU - James, Smitha R.

AU - Karpf, Adam R.

AU - Tollefsbol, Trygve O.

PY - 2011/8/1

Y1 - 2011/8/1

N2 - 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.

AB - 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.

KW - Cognition

KW - DNA methylation

KW - Dnmt1

KW - Epigenetics

KW - Healthy aging

UR - http://www.scopus.com/inward/record.url?scp=84863012853&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863012853&partnerID=8YFLogxK

U2 - 10.1007/s13148-011-0042-6

DO - 10.1007/s13148-011-0042-6

M3 - Article

C2 - 22704347

AN - SCOPUS:84863012853

VL - 2

SP - 349

EP - 360

JO - Clinical Epigenetics

JF - Clinical Epigenetics

SN - 1868-7075

IS - 2

ER -