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 Posted: Tue Oct 07, 2008 9:25 pm Post subject: Life span prediction from the rate of age-related DNA demeth |
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Exp Gerontol. 1995 Sep-Oct;30(5):475-84. Links
Life span prediction from the rate of age-related DNA demethylation in
normal and cancer cell lines.Mazin AL.
Laboratory of Molecular Bases of Ontogenesis, A.N. Belozersky
Institute of Physico-Chemical Biology, M.V. Lomonosov State
University, Moscow.
A method has been proposed for the Hayflick Limit prediction by the
analysis of the 5-methylcytosine content in DNA at earlier and later
cell passages. The following facts were used as the basis of the
method: (i) the rate of m5C loss from DNA remains approximately
constant during cell divisions and it does not depend on the cell
donor age; (ii) this rate is inversely proportional to the Hayflick
Limit as well as to the life span of cell donor species; (iii) the
period corresponded to loss of all m5C residues from the genome
coincides with or somewhat exceeds the Hayflick Limit of normal cells.
The prognosis of the Hayflick Limit has usually been found in good
agreement with the experimental evidences for various human, hamster,
and mouse cell lines. The method proposed may be used for early
detection of precrisis and cancer cells. The age-related m5C loss may
result from accumulation of the m5C-->T+C transitions occurring with
DNA methylation in every cell division.
PMID: 8557095 [PubMed - indexed for MEDLINE] |
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| Posted: Tue Oct 07, 2008 9:28 pm Post subject: Re: Life span prediction from the rate of age-related DNA d |
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Mol Biol (Mosk). 1993 Jan-Feb;27(1):160-73.Links
[Genome loses all 5-methylcytosine a life span. How is this connected
with accumulation of mutations during aging?][Article in Russian]
Mazin AL.
The 5-methylcytosine (5mC) content in liver DNA has been determined
for rats of different age. The rate of the 5mC loss from DNA is
maximal in pre- and neonatal rats, 1.28% of reduction of the 5mC
content per day, then it decreases to 0.33% and becomes minimal and
constant in adult rats, 0.028% per day. During pregnancy and the first
15 days of postnatal development rat genome loses 49% of all 5mC.
Within the next 45 days 15% of 5mC disappears, and during maximal rat
life span, about four years, 39% of the genomic 5mC may be lost. Thus,
it has been found for the first time that the animal genome loses
practically all 5mC residues during the life span. Analysis of the
literature data shows that for embryos the rate of the 5mC loss from
DNA proves to be higher than that for adult animals by 96 times for
mice, 69-for rats and 28-for cows. The rate of embryonal DNA
hypomethylation may be inversely proportional to the pregnancy
duration of species. In adult animals the rate inversely correlates
with their maximal life span and accounts for the 5mC loss from DNA of
a mouse by 0.028%, of a rat by 0.024%, of a hamster by 0.007%, of a
cow by 0.004% and of a human being by 0.0005% per day. During the
entire ontogenesis, the genome of a mouse loses 93% of all 5mC
residues, that of a rat-101% and of a cow-88%. The age-dependent loss
of 5mC from DNA is also typical for cell lines aging in vitro. It is
constant, as a rule, and correlates with the number of cell population
doublings (PD). The removal of all 5mC from DNA corresponds to 70-130
PD for human, 40-60 PD-for hamster and 6 PD- for mouse cells. In
immortal lines the level of DNA methylation is stable or grows with
age. A possible mechanism of an age-related 5mC loss from DNA is
discussed. DNA hypomethylation may result from 5mC deamination
directly at the moment of replicative DNA methylation and subsequent
reparation of the G.T mispairs which leads to accumulation of the 5mC--
[quote]T+C substitutions in the genome with each cell division. So DNA
methylation may serve as an ideal mechanism for counting cell[/quote]
divisions in vivo and in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)
PMID: 8483468 [PubMed - indexed for MEDLINE] |
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