news-review:hallmarks-of-aging
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news-review:hallmarks-of-aging [2019/11/18 00:05] marcos [Introduction] |
news-review:hallmarks-of-aging [2025/03/18 06:03] (current) marcos |
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| - | // The Hallmarks of Aging is an exemplary article for ease of reading, and doesn't really need a lot of "translation" for non-biology scientists (the goal of this site). Although it uses jargon, the sentence structure lends itself for ease of understanding. Perhaps that is why it has been cited as often as it has in other research articles. Therefore, the following review has been made as a cliff-notes version with expansions and addendums. // | ||
| ====== The Hallmarks of Aging ====== | ====== The Hallmarks of Aging ====== | ||
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| (mutation-accumulation theory) from the many that breed and die young. Also, "Selection pressure to invest metabolic resources in somatic maintenance and repair is limited; all that is required is to keep the organism in sound condition for as long as it might survive in the wild (disposable-soma theory)." (Kirkwood and Austad 2000)((Kirkwood and Austad 2000 https://www.nature.com/articles/35041682)) | (mutation-accumulation theory) from the many that breed and die young. Also, "Selection pressure to invest metabolic resources in somatic maintenance and repair is limited; all that is required is to keep the organism in sound condition for as long as it might survive in the wild (disposable-soma theory)." (Kirkwood and Austad 2000)((Kirkwood and Austad 2000 https://www.nature.com/articles/35041682)) | ||
| - | There is also a certain irony that we are in competition with our own genes for survival. Genes are more likely to survive in an evolutionary sense, if the gene is used in multiple biological functions. A mutation of a pleiotropic gene is less likely to be compatible in all the dependent functions requiring it for assembly. Thus, a pleiotropic gene is selfish at the cost of the adaptability of a species to its environment. Also at the cost of deleterious phenotypes such as aging? | + | There is also a certain irony that we are in competition with our own genes for survival. Genes are more likely to survive in an evolutionary sense, if the gene is used in multiple biological functions. A mutation of a pleiotropic gene is less likely to be compatible in all the dependent functions requiring it for assembly. Thus, a pleiotropic gene is selfish at the cost of the adaptability of a species to its environment. Also at the cost of deleterious phenotypes such as aging? In some cases not, due to [[https://en.wikipedia.org/wiki/Copy-number_variation |copy number variation]] of some genes. |
| As an experiment, fruit flies in a protected environment, were allowed to live to old age. They were allowed to breed if they outlived their counterparts. Over multiple generations, this created a progeny with longer lifespans. The long lived fruit flies had fewer offspring, suggesting that there is a trade-off between reproductive fitness and longevity. The same result, longer lifespan and fewer progeny, was also noted in mammals living on an island without predation. (Kirkwood and Austad 2000)((Kirkwood and Austad 2000 https://www.nature.com/articles/35041682)) | As an experiment, fruit flies in a protected environment, were allowed to live to old age. They were allowed to breed if they outlived their counterparts. Over multiple generations, this created a progeny with longer lifespans. The long lived fruit flies had fewer offspring, suggesting that there is a trade-off between reproductive fitness and longevity. The same result, longer lifespan and fewer progeny, was also noted in mammals living on an island without predation. (Kirkwood and Austad 2000)((Kirkwood and Austad 2000 https://www.nature.com/articles/35041682)) | ||
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| Now in the realm of science fiction, it may be possible in the future to genetically modify a mammal, or a human, to obtain longer lifespans. Maybe one way of doing so, is by being a master designer, and simplifying the convoluted mess that evolution has created. | Now in the realm of science fiction, it may be possible in the future to genetically modify a mammal, or a human, to obtain longer lifespans. Maybe one way of doing so, is by being a master designer, and simplifying the convoluted mess that evolution has created. | ||
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| + | Human genetic engineering may be necessary, as modern health care allows those with genetic diseases, like asthma, to live normal lives and reproduce. Natural selection is no longer culling the flaws. (Lesecque et al 2012)((Lesecque et al 2012 https://www.genetics.org/content/191/4/1321)) | ||
| ===== Genomic Instability ===== | ===== Genomic Instability ===== | ||
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| Repetitive elements may comprise over two-thirds of the genome. (Koning et al 2011)((Koning et al 2011 https://dx.doi.org/10.1371%2Fjournal.pgen.1002384)) These are thought to be caused by [[https://en.wikipedia.org/wiki/Mobile_genetic_elements |mobile genetic elements]] such as [[https://en.wikipedia.org/wiki/Retrotransposon |retrotransposons]], which cause gene duplication events. | Repetitive elements may comprise over two-thirds of the genome. (Koning et al 2011)((Koning et al 2011 https://dx.doi.org/10.1371%2Fjournal.pgen.1002384)) These are thought to be caused by [[https://en.wikipedia.org/wiki/Mobile_genetic_elements |mobile genetic elements]] such as [[https://en.wikipedia.org/wiki/Retrotransposon |retrotransposons]], which cause gene duplication events. | ||
| - | Transposons are [[https://en.wikipedia.org/wiki/Selfish_genetic_element |selfish genetic elements]], yet [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874221 |serve functions that are still being discovered]] (Muñoz-López and García-Pérez 2010)((Muñoz-López and García-Pérez 2010 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874221)). | + | Some transposons are [[https://en.wikipedia.org/wiki/Selfish_genetic_element |selfish genetic elements]], yet [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874221 |serve functions that are still being discovered]] (Muñoz-López and García-Pérez 2010)((Muñoz-López and García-Pérez 2010 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874221)). |
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| + | Other transposons function in the immune system, where they create novel antibodies against toxins or pathogens. | ||
| ==== Mitochondrial DNA ==== | ==== Mitochondrial DNA ==== | ||
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| Genetically modified animals with shortened or lengthened telomeres lead shorter or longer lifespans, respectively. Premature aging of telomerase-deficient mice can be reverted by reactivating telomerase in the already aged mice. "Moreover, normal physiological aging can be delayed without increasing the incidence of cancer in adult wild-type mice by pharmacological activation or systemic viral transduction of telomerase. In humans, recent meta-analyses have indicated a strong relation between short telomeres and mortality risk, particularly at younger ages." | Genetically modified animals with shortened or lengthened telomeres lead shorter or longer lifespans, respectively. Premature aging of telomerase-deficient mice can be reverted by reactivating telomerase in the already aged mice. "Moreover, normal physiological aging can be delayed without increasing the incidence of cancer in adult wild-type mice by pharmacological activation or systemic viral transduction of telomerase. In humans, recent meta-analyses have indicated a strong relation between short telomeres and mortality risk, particularly at younger ages." | ||
| + | Related article: | ||
| + | https://joshmitteldorf.scienceblog.com/2016/12/12/telomeres-too-much-of-a-good-thing | ||
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| + | Mitteldorf's article notes the existence of telomere trimming in stem cells, and then asks why telomeres that are too long would be an issue. There is a hypothesis that telomeres act to suppress gene expression, because the tails wrap back around and overlay the chromatin. Thus the presumption is that if the telomeres are too long, more genes would be suppressed than required. However, he notes there is evidence that extra-long telomeres has an overall positive effect in mice studies. | ||
| ===== Epigenetic Alterations ===== | ===== Epigenetic Alterations ===== | ||
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| Furthermore, Cruz et al showed that H3K4me3 occurrences along the chromatin has a predictable profile change with age, like sand dunes shifting in a uni-directional desert wind. The shifts increase or induce transcription at some promoters, while silencing others. Aging chromatin can also cause transcription to start from a non-promoter region, resulting in a mutated protein. 43% of yeast genes are differentially expressed after 48 hours of ageing. | Furthermore, Cruz et al showed that H3K4me3 occurrences along the chromatin has a predictable profile change with age, like sand dunes shifting in a uni-directional desert wind. The shifts increase or induce transcription at some promoters, while silencing others. Aging chromatin can also cause transcription to start from a non-promoter region, resulting in a mutated protein. 43% of yeast genes are differentially expressed after 48 hours of ageing. | ||
| - | There is much promise that supplementation of s-adenosyl methionine (SAMe) can help in maintaining chromatin methylation integrity in our 3 genomes, the nuclear, the mitochondrial, and the microbial. (Leonen 2018)((Leonen 2018 https://www.sciencedirect.com/science/article/pii/B9780128110607000036)) | + | There is much promise that supplementation of s-adenosyl methionine (SAMe) can help in maintaining chromatin methylation integrity in our 3 genomes, the nuclear, the mitochondrial, and the microbial. (Leonen 2018)((Leonen 2018 https://www.sciencedirect.com/science/article/pii/B9780128110607000036))(Detich et al 2003)((Detich et al 2003 http://www.jbc.org/content/278/23/20812.full))(Ptalzer 2014)((Ptalzer 2014 https://www.physiology.org/doi/full/10.1152/physiolgenomics.00056.2014)) |
| === AMPK === | === AMPK === | ||
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| + | --- //[[user:marcos|Marcos Reyes]] 2019/12/11 04:16// | ||
| (UNDER CONSTRUCTION) | (UNDER CONSTRUCTION) | ||
news-review/hallmarks-of-aging.1574035514.txt.gz · Last modified: 2019/11/18 00:05 by marcos
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