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news-review:hallmarks-of-aging [2019/11/18 11:02]
marcos [Histone Modifications]
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.
 +
 +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))
 + 
 +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
 +
 +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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 + --- //​[[user:​marcos|Marcos Reyes]] 2019/12/11 04:16//
  
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news-review/hallmarks-of-aging.1574074935.txt.gz · Last modified: 2019/11/18 11:02 by marcos