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To address this, a symposium titled “New Hallmarks of Ageing” was held in Copenhagen on March 2022, where leading experts gathered to discuss potential additions and recontextualizations of these aging hallmarks. The symposium highlighted the critical need for an expanded, inclusive paradigm that encompasses newly identified processes contributing to aging. The discussions suggested the integration of five additional hallmarks such as compromised autophagy, dysregulation in RNA splicing, inflammation, loss of cytoskeleton integrity, and disturbance of the microbiome. These potential new hallmarks, along with the original nine, underscore a more comprehensive understanding of the aging process, acknowledging its multifaceted nature and its profound implications for human health and longevity.{{pmid|36040386}} | To address this, a symposium titled “New Hallmarks of Ageing” was held in Copenhagen on March 2022, where leading experts gathered to discuss potential additions and recontextualizations of these aging hallmarks. The symposium highlighted the critical need for an expanded, inclusive paradigm that encompasses newly identified processes contributing to aging. The discussions suggested the integration of five additional hallmarks such as compromised autophagy, dysregulation in RNA splicing, inflammation, loss of cytoskeleton integrity, and disturbance of the microbiome. These potential new hallmarks, along with the original nine, underscore a more comprehensive understanding of the aging process, acknowledging its multifaceted nature and its profound implications for human health and longevity.{{pmid|36040386}} | ||
{| class="wikitable" | {| class="wikitable" | ||
!Level | !Level | ||
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!Category | !Category | ||
|- | |- | ||
| rowspan="6" style="background-color:hsla(195, 100%, | | rowspan="6" style="background-color:hsla(195, 100%, 85%);" |'''Molecular''' | ||
'''Level''' | '''Level''' | ||
| style="text-align:center;" |[[File:DNA Structure+Key+Labelled.pn NoBB.png|frameless|76x76px]] | | style="text-align:center; background-color:hsla(180, 100%, 85%);" |[[File:DNA Structure+Key+Labelled.pn NoBB.png|frameless|76x76px]] | ||
| style="background-color:hsla(180, 100%, | | style="background-color:hsla(180, 100%, 85%);" |'''Genomic instability''' | ||
| style="background-color:hsla(180, 100%, | | style="background-color:hsla(180, 100%, 85%);" |Accumulation of DNA damage over time leading to cellular dysfunction. | ||
| rowspan="5" |'''Primary Hallmarks''' | | rowspan="5" |'''Primary Hallmarks''' | ||
(causes damage) | (causes damage) | ||
|- | |- | ||
| style="text-align:center;" |[[File:Telomeres transparent.png|frameless|88x88px]] | | style="text-align:center; background-color:hsla(180, 100%, 85%);" |[[File:Telomeres transparent.png|frameless|88x88px]] | ||
| style="background-color:hsla(180, 100%, | | style="background-color:hsla(180, 100%, 85%);" |'''Telomere attrition''' | ||
| style="background-color:hsla(180, 100%, | | style="background-color:hsla(180, 100%, 85%);" |Reduction in the length of telomeres leading to cellular aging. | ||
|- | |- | ||
| style="text-align:center;" |[[File:Epigenome-transparent-upscale.png|frameless|85x85px]] | | style="text-align:center; background-color:hsla(180, 100%, 85%);" |[[File:Epigenome-transparent-upscale.png|frameless|85x85px]] | ||
| style="background-color:hsla(180, 100%, | | style="background-color:hsla(180, 100%, 85%);" |'''Epigenetic alterations''' | ||
| style="background-color:hsla(180, 100%, | | style="background-color:hsla(180, 100%, 85%);" |Changes in DNA methylation and histone modification affecting gene expression. | ||
|- | |- | ||
| style="text-align:center;" |[[File:Spinach (RNA).jpg|frameless|75x75px]] | | style="text-align:center; background-color:hsla(180, 100%, 85%);" |[[File:Spinach (RNA).jpg|frameless|75x75px]] | ||
| style="background-color:hsla(180, 100%, | | style="background-color:hsla(180, 100%, 85%);" |'''Splicing dysregulation''' | ||
'''(Dysregulation in RNA splicing)''' | '''(Dysregulation in RNA splicing)''' | ||
| style="background-color:hsla(180, 100%, | | style="background-color:hsla(180, 100%, 85%);" |Impaired RNA construction from DNA, leading to cellular dysfunction. | ||
|- | |- | ||
| style="text-align:center;" |[[File:Stress signaling.png|frameless|95x95px]] | | style="text-align:center; background-color:hsla(210, 100%, 85%);" |[[File:Stress signaling.png|frameless|95x95px]] | ||
| style="background-color:hsla(210, 100%, | | style="background-color:hsla(210, 100%, 85%);" |'''Loss of proteostasis''' | ||
| style="background-color:hsla(210, 100%, | | style="background-color:hsla(210, 100%, 85%);" |Disruption in protein folding and stability leading to cell damage. | ||
|- | |- | ||
| style="text-align:center;" |[[File:Macro-micro-autophagy.gif|frameless|101x101px]] | | style="text-align:center; background-color:hsla(210, 100%, 85%);" |[[File:Macro-micro-autophagy.gif|frameless|101x101px]] | ||
| style="background-color:hsla(210, 100%, | | style="background-color:hsla(210, 100%, 85%);" |'''Compromised autophagy''' | ||
| style="background-color:hsla(210, 100%, | | style="background-color:hsla(210, 100%, 85%);" | Impaired cellular maintenance through the consumption of own components. | ||
| rowspan="4" |'''Antagonistic Hallmarks''' | | rowspan="4" |'''Antagonistic Hallmarks''' | ||
(responses to damage) | (responses to damage) | ||
|- | |- | ||
| rowspan="8" style="background-color:hsla(15, 100%, | | rowspan="8" style="background-color:hsla(15, 100%, 85%);" |'''Cellular &<br>Organismal<br>Level''' | ||
| style="text-align:center; background-color:hsla(0, 100%, 85%);" |[[File:Aiga restaurant knife-fork crossed.png|frameless|75x75px]] | |||
| style="background-color:hsla(0, 100%, 85%);" |'''Deregulated nutrient sensing''' | |||
| style="background-color:hsla(0, 100%, 85%);" | Alterations in nutrient sensing pathways affecting metabolism and aging. | |||
| style="text-align:center;" |[[File:Aiga restaurant knife-fork crossed.png|frameless|75x75px]] | |||
| style="background-color:hsla(0, 100%, | |||
| style="background-color:hsla(0, 100%, | |||
|- | |- | ||
| style="text-align:center;" |[[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%, | | style="background-color:hsla(0, 100%, 85%);" |'''Mitochondrial dysfunction''' | ||
| style="background-color:hsla(0, 100%, | | style="background-color:hsla(0, 100%, 85%);" | Decrease in mitochondrial efficiency and increase in oxidative stress. | ||
|- | |- | ||
| style="text-align:center;" |[[File:DALL·E 2023-10-15 05.28.43 - Photo of senescent cells magnified under a microscope, showing their characteristic enlarged and flattened morphology. The cells are stained with a bl.png|frameless|75x75px]] | | style="text-align:center; background-color:hsla(30, 100%, 85%);" |[[File:DALL·E 2023-10-15 05.28.43 - Photo of senescent cells magnified under a microscope, showing their characteristic enlarged and flattened morphology. The cells are stained with a bl.png|frameless|75x75px]] | ||
| style="background-color:hsla(30, 100%, | | style="background-color:hsla(30, 100%, 85%);" |[[Senescent Cells|'''Cellular senescence''']] | ||
| style="background-color:hsla(30, 100%, | | style="background-color:hsla(30, 100%, 85%);" |Accumulation of non-dividing, dysfunctional cells secreting harmful factors. | ||
|- | |- | ||
| style="text-align:center;" |[[File:Stem cell differentiation.svg|frameless|106x106px]] | | style="text-align:center; background-color:hsla(30, 100%, 85%);" |[[File:Stem cell differentiation.svg|frameless|106x106px]] | ||
| style="background-color:hsla(30, 100%, | | style="background-color:hsla(30, 100%, 85%);" |'''Stem cell exhaustion''' | ||
| style="background-color:hsla(30, 100%, | | style="background-color:hsla(30, 100%, 85%);" |Decline in the regenerative capacity of stem cells affecting tissue repair. | ||
| rowspan="5" |'''Integrative Hallmarks''' | | rowspan="5" |'''Integrative Hallmarks''' | ||
(culprits of the phenotype) | (culprits of the phenotype) | ||
|- | |- | ||
| style="text-align:center;" | | | style="text-align:center; background-color:hsla(30, 100%, 85%);" | | ||
| style="background-color:hsla(30, 100%, | | style="background-color:hsla(30, 100%, 85%);" |'''Altered intercellular communication''' | ||
| style="background-color:hsla(30, 100%, | | style="background-color:hsla(30, 100%, 85%);" |Changes in cellular communication leading to inflammation and tissue dysfunction. | ||
|- | |- | ||
| style="text-align:center;" |[[File:202004 Gut microbiota.svg|frameless|75x75px]] | | style="text-align:center; background-color:hsla(30, 100%, 85%);" |[[File:202004 Gut microbiota.svg|frameless|75x75px]] | ||
| style="background-color:hsla(30, 100%, | | style="background-color:hsla(30, 100%, 85%);" |'''Microbiome disturbance''' | ||
'''(Dysbiosis)''' | '''(Dysbiosis)''' | ||
| style="background-color:hsla(30, 100%, | | style="background-color:hsla(30, 100%, 85%);" |Changes in gut microbiome affecting health and aging. | ||
|- | |- | ||
| style="text-align:center;" |[[File:Histopathology of acute and chronic inflammation of the gastro-esophageal junction, annotated.jpg|frameless|75x75px]] | | style="text-align:center; background-color:hsla(30, 100%, 85%);" |[[File:Histopathology of acute and chronic inflammation of the gastro-esophageal junction, annotated.jpg|frameless|75x75px]] | ||
| style="background-color:hsla(30, 100%, | | style="background-color:hsla(30, 100%, 85%);" |'''Inflammation''' | ||
'''(Inflammaging)''' | '''(Inflammaging)''' | ||
| style="background-color:hsla(30, 100%, | | style="background-color:hsla(30, 100%, 85%);" |Systemic inflammation contributing to aging and related diseases. | ||
|- | |- | ||
| style="text-align:center;" |[[File:Cell structure (13080952404).jpg|frameless|99x99px]] | | style="text-align:center; background-color:hsla(30, 100%, 85%);" |[[File:Cell structure (13080952404).jpg|frameless|99x99px]] | ||
| style="background-color:hsla(30, 100%, | | style="background-color:hsla(30, 100%, 85%);" |'''Altered mechanical properties''' | ||
| style="background-color:hsla(30, 100%, | | style="background-color:hsla(30, 100%, 85%);" |Changes in cellular and extracellular structure affecting tissue function. | ||
|} | |} | ||