Human lymphocytes aged in vivo have reduced levels of methylation in transcriptionally active and inactive DNA.

The amount of 5-methylated cytosine (5 mC) in the sequence CmCGG has been measured in DNA extracted from uncultured peripheral blood human lymphocytes obtained from 24 young (mean age 25) and 22 old (mean age 75) individuals. When compared with the young group the old group had significantly reduced levels of 5 mC in total genomic DNA, in transcriptionally active DNA, and in genomic DNA from which transcriptionally active sequences had been removed. In both the young and old groups transcriptionally active DNA contained 10% less 5 mC than the residual 'inactive' DNA. These results indicate that loss of genomic DNA methylation may be involved in aging in vivo and underscore the association of gene regulation with the distribution of methylation in DNA.

[1]  N. Sarkar,et al.  Integration of New Endogenous Mouse Mammary Tumor Virus Proviral DNA at Common Sites in the DNA of Mammary Tumors of C3Hf Mice and Hypomethylation of the Endogenous Mouse Mammary Tumor Virus Proviral DNA in C3Hf Mammary Tumors and Spleens , 1983, Journal of virology.

[2]  M. Monk Methylation and the X chromosome , 1986, BioEssays : news and reviews in molecular, cellular and developmental biology.

[3]  G. Romanov,et al.  Methylation of reiterated sequences in mammalian DNAs. Effects of the tissue type, age, malignancy and hormonal induction. , 1981, Biochimica et biophysica acta.

[4]  G. Margison,et al.  The in vitro lifespan of MRC-5 cells is shortened by 5-azacytidine-induced demethylation. , 1987, Experimental cell research.

[5]  A. Riggs,et al.  DNA methylation and gene function. , 1980, Science.

[6]  B. Cattanach Position effect variegation in the mouse. , 1974, Genetical research.

[7]  M. Gruber,et al.  Methylation of the chicken vitellogenin gene: influence of estradiol administration. , 1983, Nucleic acids research.

[8]  A. Bird CpG-rich islands and the function of DNA methylation , 1986, Nature.

[9]  L. Mays-Hoopes,et al.  Decreased methylation of the major mouse long interspersed repeated DNA during aging and in myeloma cells. , 1986, Developmental genetics.

[10]  D. Cooper,et al.  DNA methylation and CpG suppression. , 1985, Cell differentiation.

[11]  M. Lyon,et al.  Age related reactivation of an X-linked gene , 1987, Nature.

[12]  E. Murray,et al.  Site specific demethylation in the promoter of human gamma‐globin gene does not alleviate methylation mediated suppression. , 1987, The EMBO journal.

[13]  B. Migeon,et al.  Studies of X chromosome DNA methylation in normal human cells , 1982, Nature.

[14]  G. Poste,et al.  Effect of 5-azacytidine on DNA methylation and the malignant properties of B16 melanoma cells. , 1985, Cancer research.

[15]  J. H. Spencer,et al.  Nucleotide clusters in deoxyribonucleic acids. XII. The distribution of 5-methylcytosine in pyrimidine oligonucleotides of mouse L-cell satellite DNA and main band DNA. , 1975, Biochemical and biophysical research communications.

[16]  Howard Cedar,et al.  DNA methylation affects the formation of active chromatin , 1986, Cell.

[17]  S. Goldstein,et al.  Loss of reiterated DNA sequences during serial passage of human diploid fibroblasts , 1980, Cell.

[18]  V. Wilson,et al.  Genomic 5-methyldeoxycytidine decreases with age. , 1987, The Journal of biological chemistry.

[19]  A. Feinberg,et al.  Hypomethylation distinguishes genes of some human cancers from their normal counterparts , 1983, Nature.

[20]  M. Kastan,et al.  Distribution of 5-methyldeoxycytidine in products of staphylococcal nuclease digestion of nuclei and purified DNA. , 1985, Biochemistry.

[21]  D. Wolgemuth,et al.  Methylation of satellite sequences in mouse spermatogenic and somatic DNAs. , 1984, Nucleic acids research.

[22]  R Holliday,et al.  The inheritance of epigenetic defects. , 1987, Science.

[23]  S. Goldstein,et al.  Variability of DNA methylation patterns during serial passage of human diploid fibroblasts. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[24]  W. Diver,et al.  The majority of methylated deoxycytidines in human DNA are not in the CpG dinucleotide. , 1987, Biochemical and biophysical research communications.

[25]  A. Morley,et al.  Effect of age on lymphocyte proliferation , 1987, Mechanisms of Ageing and Development.

[26]  S. Goldstein,et al.  Human alphoid family of tandemly repeated DNA. Sequence of cloned tetrameric fragments and analysis of familial divergence. , 1985, Journal of molecular biology.

[27]  V. L. Wilson,et al.  DNA methylation decreases in aging but not in immortal cells. , 1983, Science.

[28]  R. Flavell,et al.  DNA methylation in the human γδβ-globin locus in erythroid and nonerythroid tissues , 1980, Cell.

[29]  Donald Macleod,et al.  A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA , 1985, Cell.

[30]  S. Kumar,et al.  Assembly of active chromatin. , 1986, Biochemistry.

[31]  D. Poncet,et al.  CG Sites and their nucleotide environment in the human γ-δ-β-globin gene cluster: distribution, frequency and possible frame for differential methylation , 1983 .

[32]  J. Locker,et al.  alpha-Fetoprotein gene methylation and hepatocarcinogenesis in rats fed a choline-devoid diet. , 1987, Carcinogenesis.

[33]  R. Hoffman,et al.  DNA methylation in normal and SV40-transformed human fibroblasts. , 1981, Biochemical and biophysical research communications.

[34]  H. Cedar,et al.  Organization of 5-methylcytosine in chromosomal DNA. , 1978, Biochemistry.

[35]  A. Riggs,et al.  DNA methylation, biochemistry, and biological significance , 1984 .

[36]  W. Doerfler,et al.  DNA methylation and gene activity. , 1983, Annual review of biochemistry.

[37]  L. Mays-Hoopes,et al.  Methylation and rearrangement of mouse intracisternal a particle genes in development, aging, and myeloma , 1983, Molecular and cellular biology.