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Hallmarks of Aging: Difference between revisions
→The Hallmarks in Detail
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| rowspan="3" style="text-align:center; background-color:hsla(180, 100%, 85%);" |[[File:Epigenome-transparent-upscale.png|frameless|85x85px]] | | rowspan="3" style="text-align:center; background-color:hsla(180, 100%, 85%);" |[[File:Epigenome-transparent-upscale.png|frameless|85x85px]] | ||
| rowspan="3" style="background-color:hsla(180, 100%, 85%);" |'''Epigenetic alterations''' | | rowspan="3" style="background-color:hsla(180, 100%, 85%);" |'''[[Epigenetic Alterations|Epigenetic alterations]]''' | ||
| style="background-color:hsla(180, 100%, 85%);" |'''Histone modifications''' | | style="background-color:hsla(180, 100%, 85%);" |'''Histone modifications''' are a type of epigenetic alteration that play a crucial role in regulating gene expression. Histones are proteins around which DNA is wrapped in eukaryotic cells, forming a structure known as a nucleosome. These modifications occur primarily at the tails of histone proteins and influence how tightly or loosely DNA is wound around the histones, affecting the accessibility of the DNA to various cellular machinery for processes like transcription, replication, and repair. | ||
| | |Chemical changes to histone proteins after they are formed can activate or silence gene expression and regulate the aging process.{{pmid|17320507}} | ||
| | |[[Sirtuins]] influence histone modifications: | ||
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* Mutant mice deficient in SIRT6 exhibit accelerated aging{{pmid|16439206}} | |||
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* Overexpression of SIRT1 improves aspects of health during aging but does not increase longevity{{pmid|20975665}} | |||
* Overexpression of SIRT3 reverse the regenerative capacity of aged stem cells{{pmid|23375372}} | |||
* Overexpressing ''SIRT6'' in mice have a longer lifespan<nowiki>{{pmid|22367546}}</nowiki> | |||
|Disorders in histone modification are linked with various aging-related conditions, implicating altered gene expression and protein function{{pmid|22291607}}. | |||
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| style="background-color:hsla(180, 100%, 85%);" |'''DNA methylation shift''': DNA methylation is a biochemical process involving the addition of a methyl group to the DNA molecule, specifically to the cytosine or adenine DNA nucleotides. This process is a form of epigenetic modification, which means it can affect gene expression and function without changing the DNA sequence itself. | |||
|DNA methylation generally decreases with age in certain human and mouse tissues or cell cultures.{{pmid|3611071}}{{pmid|22689993}}{{pmid|35143257}}{{pmid|35501397}} The loss of methylation in CD4<sup>+</sup> T cells is proportional to age.{{pmid|22689993}} | |||
|No direct evidence yet that altering DNA methylation patterns extends lifespan. | |||
|No direct evidence yet that altering DNA methylation patterns extends lifespan. | |||
|Progeroid syndromes exhibit DNA methylation patterns similar to normal aging, suggesting a link with aging-related diseases{{pmid|20961378}}{{pmid|16738054}}. | |||
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|''' | |'''Chromatin remodeling''' in the context of epigenetic alterations refers to the dynamic modification of the chromatin architecture to regulate access to genetic information in the DNA. Chromatin, which consists of DNA wrapped around histone proteins, can be altered or remodeled in various ways to either condense and silence gene regions or relax and activate them. This remodeling is a crucial mechanism for controlling gene expression, replication, repair, and other essential cellular processes. | ||
| | |Global canonical histone loss is regarded as a common feature of aging from yeast to humans.{{pmid|19516333}}{{pmid|24532716}}{{pmid|20890289}} | ||
| | |Flies with loss-of-function mutations in HP1α (a key chromosomal protein) have a shortened lifespan.{{pmid|22291607}} | ||
| | |Overexpression of HP1α extends longevity in flies and delays the muscular deterioration characteristic of old age.{{pmid|22291607}} | ||
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|'''Chromatin remodeling''': | |'''Chromatin remodeling''': | ||
| | |Chromatin remodeling, involving chromosomal proteins and factors like HP1α and Polycomb group proteins, changes with age. These alterations contribute to global heterochromatin loss and affect chromosomal stability{{pmid|19734887}} {{pmid|22647267}}. | ||
| | |Disruptions in chromatin remodeling factors can accelerate aging, as shown in models with loss-of-function mutations in key proteins like HP1α{{pmid|22291607}}. | ||
| | |Manipulating chromatin remodeling components may slow aging, as indicated by the extended lifespan in flies with overexpressed heterochromatin proteins{{pmid|22291607}}. | ||
| | |Alterations in chromatin remodeling are implicated in various age-related diseases and conditions, impacting genomic stability and cellular functionality{{pmid|19734887}}. | ||
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| style="text-align:center; background-color:hsla(210, 100%, 85%);" |[[File:Stress signaling.png|frameless|95x95px]] | | style="text-align:center; background-color:hsla(210, 100%, 85%);" |[[File:Stress signaling.png|frameless|95x95px]] | ||
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| style="text-align:center; background-color:hsla(0, 100%, 85%);" |[[File:Mitochondrion mini.svg|frameless|92x92px]] | | style="text-align:center; background-color:hsla(0, 100%, 85%);" |[[File:Mitochondrion mini.svg|frameless|92x92px]] | ||
| style="background-color:hsla(0, 100%, 85%);" |'''Mitochondrial dysfunction''' | | style="background-color:hsla(0, 100%, 85%);" |'''Mitochondrial dysfunction''' | ||
| style="background-color:hsla(0, 100%, 85%);" | | | style="background-color:hsla(0, 100%, 85%);" | | ||
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==History== | ==History== | ||