Revisiting the genomic hypomethylation hypothesis of aging

Archana Unnikrishnan; Niran Hadad; Dustin R. Masser; Jordan Jackson; Willard M. Freeman; Arlan Richardson

doi:10.1111/nyas.13533

Revisiting the genomic hypomethylation hypothesis of aging

Archana Unnikrishnan, Niran Hadad, Dustin R. Masser, Jordan Jackson, Willard M. Freeman, Arlan Richardson

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

The genomic hypomethylation hypothesis of aging proposes that an overall decrease in global DNA methylation occurs with age, and it has been argued that the decrease in global DNA methylation could be an important factor in aging, resulting in the relaxation of gene expression regulation and abnormal gene expression. Since it was initially observed that DNA methylation decreased with age in 1974, 16 articles have been published describing the effect of age on global DNA methylation in various tissues from rodents and humans.We critically reviewed the publications on the effect of age on DNAmethylation and the expression of the enzymes involved in DNAmethylation to evaluate the validity of the hypomethylation hypothesis of aging. On the basis of the current scientific literature, we conclude that a decrease in the global methylation of the genome occurs in most if not all tissues/cells as an animal ages. However, age-related changes in DNA methylation in specific regions or at specific sites in the genome occur even though the global DNA methylation does not change.

Original language	English (US)
Pages (from-to)	69-79
Number of pages	11
Journal	Annals of the New York Academy of Sciences
Volume	1418
Issue number	1
DOIs	https://doi.org/10.1111/nyas.13533
State	Published - 2018

Keywords

Aging
DNA methylation
DNA methylation enzymes
Dietary restriction
Gene expression
Hypomethylation

ASJC Scopus subject areas

Neuroscience(all)
Biochemistry, Genetics and Molecular Biology(all)
History and Philosophy of Science

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title = "Revisiting the genomic hypomethylation hypothesis of aging",

abstract = "The genomic hypomethylation hypothesis of aging proposes that an overall decrease in global DNA methylation occurs with age, and it has been argued that the decrease in global DNA methylation could be an important factor in aging, resulting in the relaxation of gene expression regulation and abnormal gene expression. Since it was initially observed that DNA methylation decreased with age in 1974, 16 articles have been published describing the effect of age on global DNA methylation in various tissues from rodents and humans.We critically reviewed the publications on the effect of age on DNAmethylation and the expression of the enzymes involved in DNAmethylation to evaluate the validity of the hypomethylation hypothesis of aging. On the basis of the current scientific literature, we conclude that a decrease in the global methylation of the genome occurs in most if not all tissues/cells as an animal ages. However, age-related changes in DNA methylation in specific regions or at specific sites in the genome occur even though the global DNA methylation does not change.",

keywords = "Aging, DNA methylation, DNA methylation enzymes, Dietary restriction, Gene expression, Hypomethylation",

author = "Archana Unnikrishnan and Niran Hadad and Masser, {Dustin R.} and Jordan Jackson and Freeman, {Willard M.} and Arlan Richardson",

note = "Funding Information: The efforts of authors were supported by NIH grants R01 AG045693 (A.U. and A.R.), R01EY021716 and R21EY024520 (W.M.F., D.R.M., D.R.M., and N.H.), T32EY023202 and T32AG052 363 (D.R.M.); a Senior Career Research Award from the Department of Veterans Affairs (A.R.); the Oklahoma Center for Advancement of Science and Technology (HR14-174) (W.M.F., D.R.M., D.R.M., and N.H.); the Donald W. Reynolds Foundation (A.R. and W.M.F.); and the Oklahoma Nathan Shock Aging Center (P30 AG050911).",

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doi = "10.1111/nyas.13533",

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pages = "69--79",

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AU - Hadad, Niran

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AU - Jackson, Jordan

AU - Freeman, Willard M.

AU - Richardson, Arlan

N1 - Funding Information: The efforts of authors were supported by NIH grants R01 AG045693 (A.U. and A.R.), R01EY021716 and R21EY024520 (W.M.F., D.R.M., D.R.M., and N.H.), T32EY023202 and T32AG052 363 (D.R.M.); a Senior Career Research Award from the Department of Veterans Affairs (A.R.); the Oklahoma Center for Advancement of Science and Technology (HR14-174) (W.M.F., D.R.M., D.R.M., and N.H.); the Donald W. Reynolds Foundation (A.R. and W.M.F.); and the Oklahoma Nathan Shock Aging Center (P30 AG050911).

PY - 2018

Y1 - 2018

N2 - The genomic hypomethylation hypothesis of aging proposes that an overall decrease in global DNA methylation occurs with age, and it has been argued that the decrease in global DNA methylation could be an important factor in aging, resulting in the relaxation of gene expression regulation and abnormal gene expression. Since it was initially observed that DNA methylation decreased with age in 1974, 16 articles have been published describing the effect of age on global DNA methylation in various tissues from rodents and humans.We critically reviewed the publications on the effect of age on DNAmethylation and the expression of the enzymes involved in DNAmethylation to evaluate the validity of the hypomethylation hypothesis of aging. On the basis of the current scientific literature, we conclude that a decrease in the global methylation of the genome occurs in most if not all tissues/cells as an animal ages. However, age-related changes in DNA methylation in specific regions or at specific sites in the genome occur even though the global DNA methylation does not change.

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Revisiting the genomic hypomethylation hypothesis of aging

Abstract

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