news-review:tick-tock-dna-methylation-the-epigenetic-clock-and-exceptional-longevity
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news-review:tick-tock-dna-methylation-the-epigenetic-clock-and-exceptional-longevity [2019/08/02 04:29] marcos |
news-review:tick-tock-dna-methylation-the-epigenetic-clock-and-exceptional-longevity [2019/08/05 23:20] (current) marcos [Abstract] |
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| ===== Abstract ===== | ===== Abstract ===== | ||
| - | With the advancement in science and technology, many clues are available, but not enough to have a clear picture of the cause of aging, or the traits of individuals that live long healthy lives. Scientists have not succeeded in discovering genes associated with exceptional longevity. Attempts have been made to find other genome attributes that lead to longevity, besides genes or other DNA sequences. | + | With the advancement in science and technology, many clues are available, but not enough to have a clear picture of the cause of aging, or the genomic traits of individuals that will live long healthy lives. Scientists have not succeeded in discovering genes associated with exceptional longevity. Attempts have been made to find other genome attributes that lead to longevity, besides genes or other DNA sequences. |
| DNA does not live in a void by itself. Kwok et al overview studies pertaining to molecules that attach to DNA. In particular, studies of [[https://www.nature.com/scitable/topicpage/the-role-of-methylation-in-gene-expression-1070 |DNA methylation]], the adding of methyl groups to a cytosine base of DNA. Methylation can change the activity of molecular interactions with a DNA segment. | DNA does not live in a void by itself. Kwok et al overview studies pertaining to molecules that attach to DNA. In particular, studies of [[https://www.nature.com/scitable/topicpage/the-role-of-methylation-in-gene-expression-1070 |DNA methylation]], the adding of methyl groups to a cytosine base of DNA. Methylation can change the activity of molecular interactions with a DNA segment. | ||
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| Because of the complexity of molecular interactions in an organism, cause and effect are difficult to establish. Kwok et al cover many other research studies trying to find patterns between methylation, health, and age. Research has hypothesized the existence of an epigentic clock which may be based on the methylation state. | Because of the complexity of molecular interactions in an organism, cause and effect are difficult to establish. Kwok et al cover many other research studies trying to find patterns between methylation, health, and age. Research has hypothesized the existence of an epigentic clock which may be based on the methylation state. | ||
| - | ===== Studies Overviewed in the Article ===== | + | ===== Optimal Study Design to Correlate Methylation and Longevity ===== |
| Cross-sectional studies and Longitudinal studies have been performed to investigate how epigenetic | Cross-sectional studies and Longitudinal studies have been performed to investigate how epigenetic | ||
| methylation affects aging. In cross-sectional studies, the young and old members of a population are compared. Longitudinal studies follow the same members of a population over an extended period of time, to see how aging affects their genome. | methylation affects aging. In cross-sectional studies, the young and old members of a population are compared. Longitudinal studies follow the same members of a population over an extended period of time, to see how aging affects their genome. | ||
| - | Most of the studies performed were cross-sectional, comparing younger and older cohorts, either as unrelated or family studies or twins. These studies showed possible differences in the genome from the aging process, or they showed differences resulting from disease. Depending on the disease, the genome can show early mortality or... increased longevity? | + | Most of the studies performed were cross-sectional, comparing younger and older cohorts, either as unrelated or family studies or twins. These studies showed possible differences in the genome from the aging process, or they showed differences resulting from disease. |
| Cross-sectional studies have inherent limitations:\\ | Cross-sectional studies have inherent limitations:\\ | ||
| 1. The genomes of different persons makes it hard to set a baseline.\\ | 1. The genomes of different persons makes it hard to set a baseline.\\ | ||
| 2. A higher number of confounding variables and lack of scientific_controls. \\ | 2. A higher number of confounding variables and lack of scientific_controls. \\ | ||
| - | 3. Overall insufficient information for statistically meaningful conclusions. | + | 3. Insufficient information for statistically meaningful conclusions. |
| Whereas cross-sectional studies look at different genomes of different ages at one point in time, longitudinal studies have the advantage of looking at how individual genomes change over long periods of time. | Whereas cross-sectional studies look at different genomes of different ages at one point in time, longitudinal studies have the advantage of looking at how individual genomes change over long periods of time. | ||
| - | Longitudinal limitations:\\ | + | Longitudinal study limitations:\\ |
| - | 1. Logistics difficulties.\\ | + | 1. Lack of standardization in methods for collection/extracting of blood or genetic material, and storage thereof.\\ |
| - | 2. Lengthy procedure. | + | 2. Lack of standardization for methylation analysis.\\ |
| + | 3. Time commitment for a study, and unknown time period for statistical significance. | ||
| - | Epigenetic clocks & interpretation of data | + | ===== Epigenetic Clocks & Interpretation of Data ===== |
| - | Recent researches have been performed using DNA methylation profile to calculate the | + | DNA methylation profiles estimate a chronological age, suggesting a conceptual epigenetic clock. |
| - | chronological age that has suggested the existence of Epigenetic clock; | + | |
| + | There are regions of stochastic, or random, methylation along the chromosomes. However, some isolated regions show a consistent decline in methylation density with age. In exceptionally long lived individuals, there are regions that decline less rapidly, suggesting younger epigenetic age and long-lived phenotype. | ||
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| + | Embryonic stem cells have the highest amount of chromosomal methylation. Highly methylated chromosomes are more tightly condensed, with less surface area for molecular interactions effectuating less active or disabled gene sites. | ||
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| + | In the lab, scientists can convert somatic_cells into stem cells of pluripotent nature. These cells also have a methylated state resembling embryonic stem cells. This methylated state can be thought of as having a "DNA methylation age" of zero. | ||
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| + | When scientists work with tissue cultures, the cells in the culture also have altered methylation over time, and is associated with the passage_number. "The DNA methylation profiles of mammalian cell lines differ from those of the primary tissues from which they were derived, exhibiting increasing divergence from the in vivo methylation profile with extended time in culture." ((https://dx.doi.org/10.1186%2Fs13059-014-0576-y)) | ||
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| + | There has been efforts into finding key locations, or loci, along the chromosome, in hopes of isolating or reducing the complexity of a statistical model of aging. These loci are compared to a person's calendar age. | ||
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| + | Individuals that skew from the mean towards a younger "DNA methylation age", compared to their physical age, tend to live longer lives. | ||
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| + | While the studies may aspire to find a biological process for aging, currently the methylated loci are only age indicators, like measuring the amount of wrinkles on a person's face, or the quality of one's teeth. | ||
| * Bocklandt et al predicted the human age using DNA methylation profile in a study using saliva sample from 34 male monozygotic twin pairs between 21-45 years of age. | * Bocklandt et al predicted the human age using DNA methylation profile in a study using saliva sample from 34 male monozygotic twin pairs between 21-45 years of age. | ||
| * Horvath et al researched on over 8000 samples revealing that DNA methylation age is zero for embryos. | * Horvath et al researched on over 8000 samples revealing that DNA methylation age is zero for embryos. | ||
| * Hannum et al, further developed the concept of the epigenetic clock in a cohort of 656 participants aged 19–101 years from whole blood. | * Hannum et al, further developed the concept of the epigenetic clock in a cohort of 656 participants aged 19–101 years from whole blood. | ||
| - | * Marioni et al calculated the difference between an individual’s chronological age and DNA methylation age (?age), and demonstrated that this difference could significantly predict all-causes of mortality in later life. | + | * Marioni et al calculated the difference between an individual’s chronological age and DNA methylation age, and demonstrated that this difference could significantly predict all-causes of mortality in later life. |
| * Gross et al conducted an analysis on 137 HIV+ men. He found out HIV infection leads to an average advancement of 4.9 years, increasing expected mortality risk by 19%. | * Gross et al conducted an analysis on 137 HIV+ men. He found out HIV infection leads to an average advancement of 4.9 years, increasing expected mortality risk by 19%. | ||
| - | Hence these studies suggest that some of the epigenetic loci are altered with disease processes and ultimately with mortality. | + | ===== Unresolved Issues ===== |
| - | + | ||
| - | UNRESOLVED ISSUES: | + | |
| * Horvath et al studied on centenarians and younger individuals, suggesting that the chronological age was underestimated by 8.6 years. If this is the case then it could affect the power of our cross-sectional longevity studies to detect the loci. | * Horvath et al studied on centenarians and younger individuals, suggesting that the chronological age was underestimated by 8.6 years. If this is the case then it could affect the power of our cross-sectional longevity studies to detect the loci. | ||
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| --- //[[user:marcos|Marcos Reyes]] 2019/07/30 04:38//\\ | --- //[[user:marcos|Marcos Reyes]] 2019/07/30 04:38//\\ | ||
| --- //[[user:sobia|Sobia Syed]] 2019/07/30 04:38// | --- //[[user:sobia|Sobia Syed]] 2019/07/30 04:38// | ||
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| + | ===== Related Content ===== | ||
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| + | https://www.nature.com/scitable/topicpage/the-role-of-methylation-in-gene-expression-1070 | ||
news-review/tick-tock-dna-methylation-the-epigenetic-clock-and-exceptional-longevity.1564720162.txt.gz · Last modified: 2019/08/02 04:29 by marcos
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