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 [2019/08/03 19:42] marcos [Optimal Study Design to Correlate Methylation and Longevity] |
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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| 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:\\ | ||
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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)) | 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)) | ||
| - | There has been efforts into finding key locations, or loci, along the chromosome, in hopes of isolating or reducing the complexity of the aging determinant. However, these loci are based on statistical models, and the biology of aging remains undetermined. | + | 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%. | ||
news-review/tick-tock-dna-methylation-the-epigenetic-clock-and-exceptional-longevity.1564861351.txt.gz · Last modified: 2019/08/03 19:42 by marcos
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