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Medicine Science

DNA Modifications Change As We Age 62

Posted by Unknown Lamer
from the activate-the-gene-sequence dept.
sciencehabit writes "As we age, the core of our biological being — the sequence of our DNA, which makes up our genes — remains the same. Yet recent research suggests that more subtle chemical changes to our DNA occur as we age. Now, a comparison of the DNA of a newborn baby with that of a centenarian shows that the scope of these changes can be dramatic, and they may help explain why our risk of cancer and other diseases increases as we get older."
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DNA Modifications Change As We Age

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  • can change them back
  • he core of our biological being — the sequence of our DNA, which makes up our genes — remains the same

    I was under the impression that it was known that it doesn't: when the molecule replicates, there could be chunks that failed to replicate perfectly, propagating an error: obviously there are redundancies in place, but eventually (and statistically) the error builds up. I vaguely remember the explanation relying on arguments on physics, as to how the molecule may "snap" incorrectly at the end (or some other point). Can someone more adept in biology verify (or dismiss) this?

    • No more adept at biology, but I read that the replication is most susceptible to errors at the ends, which is why there are chunks of non-coding DNA (telomeres) there which get shorter with each replication.

      • Re: (Score:2, Funny)

        by Anonymous Coward

        So what you're saying is that our DNA has split ends?
        So we need DNA's version of Head and Shoulders then?

    • by samoanbiscuit (1273176) on Tuesday June 12, 2012 @03:40AM (#40292943)

      What the article is discussing is how methylation differs between very young and very old people. The abstract of the original paper may be more instructive:

      Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA had a lower DNA methylation content and a reduced correlation in the methylation status of neighboring cytosine—phosphate—guanine (CpGs) throughout the genome in comparison with the more homogeneously methylated newborn DNA. The more hypomethylated CpGs observed in the centenarian DNA compared with the neonate covered all genomic compartments, such as promoters, exonic, intronic, and intergenic regions. For regulatory regions, the most hypomethylated sequences in the centenarian DNA were present mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. We extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray that reinforced the observation of more hypomethylated DNA sequences in the advanced age group. WGBS and 450,000 analyses of middle-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level.

      what I understand from that wall of text is this: The paper puts forward is another factor that contributes to errors cropping up causing diseases associated with old age, like cancer. Methylation controls (or should that be retards?) transcriptional activity, so a change in methylation patterns, or a drop in the occurence of methylation, would change the types of activities the DNA undergoes, and change the probability (probably upwards) of things going wrong.

      I am but a lowly undergrad who doesn't pay as much attention is lectures as he should, so please someone correct me if I am wrong.

      • by Anonymous Coward

        A lowly undergrad who bothered to read and think about the article.

        • Re: (Score:2, Funny)

          by Anonymous Coward

          A lowly undergrad who bothered to read and think about the article.

          BURN HIM!

      • by Anonymous Coward
        Over time the different cells of your body become more genetically different. In a creature that has very specialized and very dependent organs, how does your body especially the immune system (which is also made of cells) know which cells aren't part of you and can be killed? It might be too aggressive- then you have autoimmune diseases, or it might be too lax then you are more susceptible to cancer or parasites.

        In organisms that are not so specialized and not so dependent, it doesn't matter so much - one
      • by Anonymous Coward on Tuesday June 12, 2012 @04:32AM (#40293103)

        Epigeneric drift is not changes of the sequence of genes just their expression. In their example genes are surpressed by the presence of methyl groups attached to some parts of the DNA molecule.

        • I am sorry if I was not clear enough, but I certainly realize what epigenetic drift is and that's what I was alluding to with my vague "things going wrong" statement.
      • by tancque (925227)

        I concur with your understanding of the text.

        In reference thereof: I know that methylation is part of the regulation of gene expression. I just keep wondering if the increased methylation is normal for changed expression-patterns of genes as we switch from growing to maturity. If so, methylation should not be coupled to aging, but to maturing.

        Sorry if my english is not up to scratch.

    • by c0lo (1497653)

      What exactly should stay the same? The "DNA/genes", "the changes (which themselves modify with age) - thus the DNA/genes are actually expected to change, but always in a given way" or the "modification of the changes"?

      Errr... what!!!? Exactly my point: what the hell means "DNA modifications change with age" in the context of "the sequence of our DNA, which makes up our genes, remains the same"?

      • by samoanbiscuit (1273176) on Tuesday June 12, 2012 @04:26AM (#40293089)
        It means that although the DNA will remain the same, how it is transcripted into proteins (and how often, and in reaction to what stimuli) changes. That is the purview of epigenetic study (the epi- prefix meaning over or above). Here's a useful link [wikipedia.org].
        • by c0lo (1497653)

          It means that although the DNA will remain the same, how it is transcripted into proteins (and how often, and in reaction to what stimuli) changes. That is the purview of epigenetic study (the epi- prefix meaning over or above). Here's a useful link [wikipedia.org].

          Thanks. So the correct title should be: "The DNA transcription into proteins changes with age"?

          • Not necessarily. Headlines are a bitch to write, even when you know all about the topic (and I most certainly don't). From what I have hastily read in order to answer your question (Where's Samantha Wright, biologist and purveyor of car analogies extraordinaire, when you need her?), methylation's function in retarding transcription is just one factor. Another one is that methylation leads to the formation of heterochromatin, which is a lot more important in ways that I really should know if I want to pass m
          • A major factor in what changes the transcription is methylation, which adds a methyl group to cytosine, "turning off" the gene it's attached to. The sequence itself is not changed, as cytosine becomes methyl cytosine (or whatever it's called) and not some other base, but the DNA has still been modified with the methyl group.
    • But it seems if we reproduce at a later age, we make better fathers. http://m.timesofindia.com/life-style/health-fitness/health/Offspring-of-older-fathers-may-live-longer/articleshow/14057473.cms [timesofindia.com]
      • by mcgrew (92797) *

        The one I read didn't exactly say that. It said that if your father was older you would likely live longer because you weren't stillborn. Older fathers tend to have weaker sperm and greater chance that the fetus will not survive, becoming a father at an older age means that your cells are "younger" than other people your age, including your sperm cells. If all your great gransparents lived to be a hundred, chances are you will, too. People age at different rates; I know folks twenty years younger than me wh

  • I haven't read the actual original paper because i'm guessing I don't have the appropriate background to understand it. But based on the summary, I'm curious... If there are changes with age, would these differences be passed on to offspring? I assume that some of these aging effects are similar from person to person, so if they are passed on, I imagine that would mean there are statistically significant differences in certain traits based on the age of the parents?

    Is anyone more knowledgeable in the field

    • by Coisiche (2000870) on Tuesday June 12, 2012 @05:20AM (#40293321)

      Biology is by far my weakest science and I'm not qualified at all to comment, but I just read two articles today which suggests that older fathers have longer lived children...

      Here [sciencenews.org] and here [bbc.co.uk].

      • by drinkypoo (153816)

        I haven't read them and won't but I've read articles that older fathers have children with more health problems. Apparently non-fatal ones :)

        • by Coisiche (2000870)

          Well, it could be a case of longer duration not necessarily being better.

          Kinda like in the same way that Prometheus is longer than many other films...

      • The reason for this is obvious... older fathers have better genes than younger ones, if you average over the complete population, because they survived for a longer period of time, plus perhaps the fact that they were considered sufficiently attractive at their old age to produce offspring.

        It doesn't mean that you should wait until you're older to have children, unless, of course, you want to serve the greater interest of humanity.

        • You didn't rtfa, did you? It's known that telomeres lengthen with age, and that longer telomeres are known to protect genes from damage. What the study found was
          that the longer telomeres (from the father) get passed on to the children. So it has nothing to do with survival, in this case.

          At any rate, you could eliminate that factor by comparing lifespans of older vs. younger siblings. I don't know if that was done here, but a follow-up study could do that.

          • I thought telomeres shorten as you age with each cell division. It's why alcohol and tobacco users biologically age faster than non substance abusers. I've personally seen a 36yrl women look like she's in her 60s. The thick leathery skin, bags under the eyes, and excessive skin wrinkles are proof of that. To my knowledge, such damage can't be reversed.

            • Yeah, I was wondering about that...The article seemed to contradict my recollection, but I assumed my memory was at fault (what with my shortened telomeres). So I looked on wikipedia and found that, while most cells get shorter telomeres with age, sperm is different. Telomeres in sperm lengthen. What a weird world we live in.

              • That's real interesting! It's almost natures way of honing in on the optimal age limit an animal should live. As a species, it might be more of a benefit to live fast and die young (while reproducing along the way) than to live longer and have fewer children. An optimal turnover rate that can change back and forth depending on environmental stresses.

                Not to be racist here (because we're all human after all), but that might explain why black Africans are at one end of the life spectrum compared to say the Jap

      • ... or maybe it's just that older children have more fathers. :)
    • The changes outlined refer to methylation, not to actual dna change. The sequence is the same as when you were born (for most part), but methyl groups attach to certain genes to turn them off and detach from other ones to turn them on. This stuff isn't passed to offsprings, they're just switches that are placed on the dna. So, it turns out the old people have the genes that increase chance of cancer/diabetes turned on while babies with the same genes have them turned off, and a middle aged adult is in betwe

  • by jd (1658) <imipak @ y a h o o .com> on Tuesday June 12, 2012 @05:06AM (#40293253) Homepage Journal

    As we age, the core of our biological being — the sequence of our DNA, which makes up our genes — remains the same.

    This was falsified several years ago when it was shown that retrotranspons alter the sequence of DNA in each cell dynamically continuously. Not only that, but cells are altered differently, so a person's cells diverge as they age. The paper is usually paywalled but I have a copy thanks to the generosity of the authors, if anyone wants a copy.

    Sorry, but as a matter of principle I automatically reject any claim that has as its central tenant a theory that has already been falsified. Keep up or keep the hell out.

    • by samoanbiscuit (1273176) on Tuesday June 12, 2012 @05:11AM (#40293271)
      TFA is a news fluff piece. The abstract of the actual paper [pnas.org] they are referring to does not include that bit of dogma
    • by radtea (464814)

      Sorry, but as a matter of principle I automatically reject any claim that has as its central tenant a theory that has already been falsified.

      Furthermore, our understanding of epigenetics makes rubbish of the claim that our DNA is "the core of our biological being." Biology does not have a "core" in the relevant reductionist sense. It has a number of important sub-systems that operate together. DNA is not a blueprint, the cell is not a factory. Claims that we can safely ignore everything except our coding regions are just nonsense, based on decades-old ignorance.

      • by jd (1658)

        I would absolutely agree. It's not made any simpler when you consider that a given human cell has two distinct types of DNA (and maybe once had many more), that nucleic DNA contains retroviruses and other non-human DNA components, and that there's something like 5,000 non-human species in the body, comprising 10x as many cells as there are human cells.

        When you start examining thousands of distinct forms of DNA, any of which may have epigenetic components, you're looking at a system of mindblowing proportion

    • If true, it would fall into the "Duuuuuh category" --- anyone who has been existing for awhile is sure to experience mutations through the normal course of life, solar rads, etc., etc., ad infinitum.
  • by Grayhand (2610049) on Tuesday June 12, 2012 @05:43AM (#40293407)
    It sounds like Pak Protectors. In his version of reality the age based changes originally had a purpose. The fact there's a genetic change matches with his scenario. Just interesting how science fiction and reality often converge.
  • by pr0nbot (313417)

    This article isn't about GMO, but stuff like this is one of the reasons I think we should hold off GMO for the moment. It seems to me we keep discovering things that surprise us -- epigenetics, and the unexpected extent of horizontal gene transfer, to name two recent ones -- which would suggest to me that we ought to limit ourselves to more research rather than large scale exploitation, for a while at least. (There are larger, non-scientific concerns that are the main reason I'm wary of GMO, but this is one

  • FTA:

    "The great secret that all old people share is that you really haven't changed," wrote the late novelist Doris Lessing. "Your body changes, but you don't change at all."

    I'm sorry to say thats BS. I'm in my 40s now and I'm a rather different person to the arrogant know-it-all teenager I used to be - different attitude to life, different musical tastes , different temperament, a lot more worldy wise etc. And in another 40 years - if i live that long - I'm sure I'll be different to what I am now. Its not j

    • Over 20 years ago some study on the male brain came out. They took mri's of the male brain at different ages and found that there was an an actual physical change to the brain at around the age of forty. The brain actually 'changed'! Most men I've spoke with agreed that around age 40 is when they stopped acting like kids and began to take their lives more seriously. Of course, some guys still stayed the jerks they always were, but mostly guys begin to start to question their behavior around this time.
    • by mcgrew (92797) *

      "The great secret that all old people share is that you really haven't changed," wrote the late novelist Doris Lessing. "Your body changes, but you don't change at all."

      I'm sorry to say thats BS

      I'm 60, and I agree with you. Lessig was wrong. I'm not even the same man I was when I was 40.

      Its not just the body that changes , the mind changes too.

      Of course it does. The brain changes, just like every other organ, and the mind resides within the brain.

  • Yes.. a dupe of an AC post.. frigging Safari keeps logging out of Slash on every page click. Grr.. And on something I care about (Doris Lessing, one of my fave authors).

    FTA: "The great secret that all old people share is that you really haven't changed," wrote the late novelist Doris Lessing

    Clearly a well-researched piece.. the only problem - Doris Lessing isn't dead.
  • by kiep (1821612)
    its because we eat shit that morphs our bodies

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