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After reading Lifespan by David Sinclair I'm curious if there is any evidence against aging being caused by loss of information in genome and epigenome of 3.7*1013 cells in human body.

Specifically has anyone compared the genome and epigenome of the same humans at different ages?

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  • $\begingroup$ It's important to mention the alternate hypothesis of not loss of information but different information. Taking the telomere shortening example, that is straightforward loss, but that DNA isn't informational really; rather it plays a structural role in the cell such that when it's lost it gets hard to segregate chromosomes. The other mutations and epimutations aren't (necessarily) loss of information, but on average the substitution of different information and rearrangement of the existing information. $\endgroup$
    – Maximilian Press
    Dec 15, 2020 at 5:44

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By loss of genome, I think he is referring to the shortening of telomeres. This study compares the length of telomeres of human epidermal cells. The authors report that over time, the telomeres do shorten. They also report on the rate of loss of around 32 base pairs per year. Thus there is loss of some genomic information over the age of an individual.

However, the loss of epigenomic information is trickier. The primary reason for it being some regions of the genome have been shown to lose DNA methylation marks whereas others gain it. However, leaving that aside, there is comprehensive proof that DNA methylation changes with age. This study on female peripheral leukocytes shows that approximately 350 regions (known as CpG islands) which are differentially methylated with age. Of these 350, 250 loci become hypermethylated i.e. methylation increases with age while the opposite happens for the remaining 150 loci.

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  • $\begingroup$ Thanks for the explanations. Very helpful! In the 1st paper when the scientists use 13.8±1.0 kb, does kb mean kilo bytes of base pair ATCGs so 1 kb = 1000 bytes = 8000 bits 0s && 1s representing ATCG... where A&&T = 00, T&&A = 01, C&&G = 10, && G&&C = 11 ? $\endgroup$
    – letter Q
    Dec 14, 2020 at 20:59
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    $\begingroup$ @Wang-Zhao-LiuQ The kb in biology means kilo base pairs. So 13.8 kb is 13800 base pairs. In some publications the unit kbp or bp is used to avoid confusion. $\endgroup$
    – Roni Saiba
    Dec 15, 2020 at 1:57
  • $\begingroup$ Thanks! I think I should rephrase the question is aging caused by the change of genetic information? Losing 32 base pairs or gaining 32 base pairs could both contribute to expressions of genes that cause signs of aging. $\endgroup$
    – letter Q
    Dec 15, 2020 at 4:22
  • $\begingroup$ Your second sentence is correct. However, keep in mind that it is not entirely clear whether loss of telomeres causes aging or is a result of aging. For example, mice have short lifespans but less degradation of telomeres compared to humans. You may want to explore some literature on how metabolism affects aging process as well. $\endgroup$
    – Roni Saiba
    Dec 15, 2020 at 14:08
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From what I know, I would expect that no one has performed a similar experiment to what you propose. Sequencing a genome is still rather expensive and inaccurate. Some parts of the DNA can’t be sequenced at all and most methods still rely on comparing the sequencing reads to a reference genome, making these kinds of predictions harder. Getting snapshots of an epigenome (chromatine modifications, transcription factors) to the accuracy that you can detect a notable difference after a few years is even harder.

Also, by analyzing the genome of a given somatic cell, the cell is being destroyed and not available to test it again after a couple of years to see if relevant mutations occurred.

In short: Sinclair‘s predictions are probably hard to verify at this point.

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  • $\begingroup$ Have any ideas on how to analyze the genome of a somatic cell without destroying it? Can it be cloned perfectly && then we destroy the cloned cell for analyzing? $\endgroup$
    – letter Q
    Dec 14, 2020 at 22:32
  • $\begingroup$ This runs into a similar problem: cloning a cell involves removing it from the tissue. I’m not an experimentalist though. Maybe it’s achievable with a cell culture. Using a living organism you would have to come up with something novel, probably. $\endgroup$
    – user859786
    Dec 15, 2020 at 17:02

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