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Hallmarks of Aging: Difference between revisions
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[[File:The Nine Hallmarks of Aging.jpg|thumb|The original nine hallmarks of aging as proposed by López-Otín and colleagues in 2013{{pmid|23746838}}]] | |||
Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. The '''hallmarks of aging''' are the types of biochemical changes that occur in all organisms that experience biological aging and lead to a progressive loss of physiological integrity, impaired function and, eventually, death. They were first listed in a landmark paper in 2013{{pmid|23746838}} to conceptualize the essence of biological aging and its underlying mechanisms. | Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. The '''hallmarks of aging''' are the types of biochemical changes that occur in all organisms that experience biological aging and lead to a progressive loss of physiological integrity, impaired function and, eventually, death. They were first listed in a landmark paper in 2013{{pmid|23746838}} to conceptualize the essence of biological aging and its underlying mechanisms. | ||
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The original authors of the nine hallmarks of aging update the set of proposed hallmarks after a decade.{{pmid|36599349}} | The original authors of the nine hallmarks of aging update the set of proposed hallmarks after a decade.{{pmid|36599349}} | ||
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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|Mitochondrial dysfunction]]''' | | style="background-color:hsla(0, 100%, 85%);" |'''[[Mitochondrial Dysfunction|Mitochondrial dysfunction]]''' | ||
| style="background-color:hsla(0, 100%, 85%);" | Decrease in mitochondrial efficiency and increase in oxidative stress. | | style="background-color:hsla(0, 100%, 85%);" | Decrease in mitochondrial efficiency and increase in [[Oxidative Stress|oxidative stress]]. | ||
|2013 | |2013 | ||
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|2013 | |2013 | ||
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=== Potential Hallmarks of Aging === | === Potential Hallmarks of Aging === | ||
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== The Hallmarks in Detail == | == The Hallmarks in Detail == | ||
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| style="text-align:center; background-color:hsla(180, 100%, 85%);" |'''[[Genomic Instability|Genomic instability]]'''[[File:DNA Structure+Key+Labelled.pn NoBB.png|frameless|76x76px]] | | style="text-align:center; background-color:hsla(180, 100%, 85%);" |'''[[Genomic Instability|Genomic instability]]'''[[File:DNA Structure+Key+Labelled.pn NoBB.png|frameless|76x76px]] | ||
| style="background-color:hsla(180, 100%, 85%);" |Damange in the DNA are formed mainly through oxidative stress and environmental factors.{{pmid|15123782}} A number of molecular processes work continuously to repair this damage.{{pmid|15703726}} | | style="background-color:hsla(180, 100%, 85%);" |Damange in the DNA are formed mainly through [[Oxidative Stress|oxidative stress]] and environmental factors.{{pmid|15123782}} A number of molecular processes work continuously to repair this damage.{{pmid|15703726}} | ||
|DNA damage accumulates over time{{pmid|23398157}} | |DNA damage accumulates over time{{pmid|23398157}} | ||
|Deficient DNA repair causes premature aging{{pmid|19812404}} | |Deficient DNA repair causes premature aging{{pmid|19812404}} | ||
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| style="text-align:center; background-color:hsla(210, 100%, 85%);" |'''[[Disabled Macroautophagy|Disabled macroautophagy]]''' | | style="text-align:center; background-color:hsla(210, 100%, 85%);" |'''[[Disabled Macroautophagy|Disabled macroautophagy]]''' | ||
[[File:Macro-micro-autophagy-transparent.png|frameless|101x101px]] | [[File:Macro-micro-autophagy-transparent.png|frameless|101x101px]] | ||
| style="background-color:hsla(210, 100%, 85%);" |'''Disabled macroautophagy''', often referred as impaired or dysfunctional autophagy, is a condition where the cellular process of autophagy—specifically the macroautophagy pathway—is disrupted or less effective. Autophagy is a critical cellular process for degrading and recycling damaged organelles, misfolded proteins, and other cellular debris. Macroautophagy involves the engulfment of these unwanted materials into vesicles called autophagosomes, which then fuse with lysosomes where the contents are degraded and recycled. When macroautophagy is disabled or impaired, cells accumulate damaged proteins and organelles, leading to cellular dysfunction and contributing to various diseases, particularly those related to aging and neurodegeneration. This loss of a crucial cellular "cleanup" mechanism can result in increased oxidative stress, disrupted cellular homeostasis, and an acceleration of the aging process. | | style="background-color:hsla(210, 100%, 85%);" |'''Disabled macroautophagy''', often referred as impaired or dysfunctional autophagy, is a condition where the cellular process of autophagy—specifically the macroautophagy pathway—is disrupted or less effective. Autophagy is a critical cellular process for degrading and recycling damaged organelles, misfolded proteins, and other cellular debris. Macroautophagy involves the engulfment of these unwanted materials into vesicles called autophagosomes, which then fuse with lysosomes where the contents are degraded and recycled. When macroautophagy is disabled or impaired, cells accumulate damaged proteins and organelles, leading to cellular dysfunction and contributing to various diseases, particularly those related to aging and neurodegeneration. This loss of a crucial cellular "cleanup" mechanism can result in increased [[Oxidative Stress|oxidative stress]], disrupted cellular homeostasis, and an acceleration of the aging process. | ||
While originally considered under hallmark '''altered proteostasis''', autophagy regulates a number of other hallmarks of ageing such as DNA repair and nutrient sensing/metabolism{{pmid|29626215}}, and hence it was proposed to be categorized as an integrative hallmark. | While originally considered under hallmark '''altered proteostasis''', autophagy regulates a number of other hallmarks of ageing such as DNA repair and nutrient sensing/metabolism{{pmid|29626215}}, and hence it was proposed to be categorized as an integrative hallmark. | ||
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| style="text-align:center; background-color:hsla(0, 100%, 85%);" |'''[[Deregulated Nutrient Sensing|Deregulated nutrient sensing]]''' | | style="text-align:center; background-color:hsla(0, 100%, 85%);" |'''[[Deregulated Nutrient Sensing|Deregulated nutrient sensing]]''' | ||
[[File:Aiga restaurant knife-fork crossed.png|frameless|75x75px]] | [[File:Aiga restaurant knife-fork crossed.png|frameless|75x75px]] | ||
| style="background-color:hsla(0, 100%, 85%);" | | | style="background-color:hsla(0, 100%, 85%);" |'''Deregulated nutrient sensing''' refers to the body's declining ability to properly manage and respond to nutrients, such as fats, sugars, and proteins, as we get older. Normally, our bodies have finely tuned systems that detect when we eat and use these nutrients efficiently for energy and repair. However, with age, these systems start to malfunction. This means our body might not handle sugars well, leading to conditions like diabetes, or it might struggle with managing fats, leading to issues like high cholesterol. Essentially, Deregulated Nutrient Sensing is when our body's 'nutrient management system' becomes less efficient and accurate with age, leading to various metabolic and health problems. | ||
| | |Deregulated nutrient sensing ability takes place upon aging.{{pmid|31249645}} | ||
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|The significance of nutrient sensing throughout the aging process has been first established in the prominent observation that decreased food intake in rats prolongs lifespan relative to ad libitum fed controls.{{pmid|2520283}} | |||
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== Correlation to Age-Related Diseases == | == Correlation to Age-Related Diseases == | ||
[[File:Relationship between the hallmarks of aging and the age-related diseases.jpg|thumb|Relationship between the hallmarks of aging and the age-related diseases as revealed by the number of corelated documents{{pmid|38095562}}]] | [[File:Relationship between the hallmarks of aging and the age-related diseases.jpg|thumb|Relationship between the hallmarks of aging and the age-related diseases as revealed by the number of corelated documents{{pmid|38095562}}]] | ||
This section explores the correlations between the aging hallmarks and the age-related diseases, as reflected in the number of documents in the CAS Content Collection. Generally, cellular senescence, mitochondrial dysfunction, lipid metabolism disorders, and inflammaging appear as related to multiple pathologies.{{pmid|38095562}} | |||
Some particular correlations are noteworthy: | Some particular correlations are noteworthy: | ||
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*Alzheimer disease–mitochondrial dysfunction correlation: Alzheimer’s disease is the most frequent source of age-related neurodegeneration and cognitive impairment. A growing body of evidence implicates mitochondrial dysfunction as a common pathogenic mechanism involved in many of the features of the Alzheimer’s patients brain, such as formation of amyloid plaques and neurofibrillary tangles.{{pmid|34063708}} | *Alzheimer disease–mitochondrial dysfunction correlation: Alzheimer’s disease is the most frequent source of age-related neurodegeneration and cognitive impairment. A growing body of evidence implicates mitochondrial dysfunction as a common pathogenic mechanism involved in many of the features of the Alzheimer’s patients brain, such as formation of amyloid plaques and neurofibrillary tangles.{{pmid|34063708}} | ||
*Altogether, there is significant correlation between mitochondrial dysfunction and the majority of age-related diseases including diabetes, inflammation, obesity, neurodegenerative disorders, cardiovascular diseases, and cancer.{{pmid|29257072}} Mitochondria are vital in regulation of energy and metabolic homeostasis. Proper mitochondrial functions, including cellular energy production and control of oxidative stress, are in strong relation with the accurate performance of brain, cognition, and the overall health.{{pmid|33808109}} | *Altogether, there is significant correlation between mitochondrial dysfunction and the majority of age-related diseases including diabetes, inflammation, obesity, neurodegenerative disorders, cardiovascular diseases, and cancer.{{pmid|29257072}} Mitochondria are vital in regulation of energy and metabolic homeostasis. Proper mitochondrial functions, including cellular energy production and control of [[Oxidative Stress|oxidative stress]], are in strong relation with the accurate performance of brain, cognition, and the overall health.{{pmid|33808109}} | ||
*Liver fibrosis–lipid metabolic disorders correlation: Liver plays a key role in lipid metabolism; therefore alterations in hepatic lipid metabolism can be a factor in development of chronic liver disease. Furthermore, chronic liver disease can impact hepatic lipid metabolism causing alterations in circulating lipid levels contributing to dyslipidemia.<ref>Arvind A.; Osganian S. A.; Cohen D. E.E.; C K.. Lipid and Lipoprotein Metabolism in Liver Disease. In Endotext [Internet]; Feingold K. R., Anawalt B., Blackman M. R., Eds.; MDText.com, Inc.: South Dartmouth, 2019. [Google Scholar]</ref> Likewise, the liver plays an essential role in lipid metabolism, certain steps of lipid synthesis, and transport. Therefore, abnormal lipid profiles and liver dysfunctions are expectedly closely correlated.{{pmid|22312394}} | *Liver fibrosis–lipid metabolic disorders correlation: Liver plays a key role in lipid metabolism; therefore alterations in hepatic lipid metabolism can be a factor in development of chronic liver disease. Furthermore, chronic liver disease can impact hepatic lipid metabolism causing alterations in circulating lipid levels contributing to dyslipidemia.<ref>Arvind A.; Osganian S. A.; Cohen D. E.E.; C K.. Lipid and Lipoprotein Metabolism in Liver Disease. In Endotext [Internet]; Feingold K. R., Anawalt B., Blackman M. R., Eds.; MDText.com, Inc.: South Dartmouth, 2019. [Google Scholar]</ref> Likewise, the liver plays an essential role in lipid metabolism, certain steps of lipid synthesis, and transport. Therefore, abnormal lipid profiles and liver dysfunctions are expectedly closely correlated.{{pmid|22312394}} | ||