Difference between revisions of "Hallmarks of aging"

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The Strategies for Engineered Negligible Senescence (SENS) are a classification of potential [[life extension]] therapies by the type of age-related damage they target. It was created by [[Aubrey de Grey]] in 2000 and published in his 2007 book ''[[Ending Aging]]''. The seven types of damage listed are:
 
The Strategies for Engineered Negligible Senescence (SENS) are a classification of potential [[life extension]] therapies by the type of age-related damage they target. It was created by [[Aubrey de Grey]] in 2000 and published in his 2007 book ''[[Ending Aging]]''. The seven types of damage listed are:
# Cell loss/atrophy
+
# '''Cell loss''': fewer cells in tissue, causing deterioration, due to impaired dead-cell replacement by stem cells<ref name="replenisens">[https://www.sens.org/our-research/intro-to-sens-research/replenisens/ "RepleniSENS"]. ''SENS Research Foundation''. "Some of these damaged cells are repaired, but others are either destroyed, or forced into a dysfunctional ‘senescent’ state where they can no longer divide, or commit ‘cellular suicide’ (apoptosis) for the greater good of the body. Some of the lost cells are replaced by the pools of specialized, tissue-specific stem cells, but the degenerative aging process makes these stem cell pools less effective at repair over time."</ref>
# Extracellular junk
+
# '''Extracellular junk''': old proteins (example: Alzheimer's plaque) impairing cell/tissue function<ref name="amylosens">[https://www.sens.org/our-research/intro-to-sens-research/amylosens/ "AmyloSENS"]. ''SENS Research Foundation''. "Extracellular junk is accumulations of sticky, malformed proteins that no longer serve their function, but instead impair cell or tissue function by their presence. [...] The most well-known form of extracellular junk is beta-amyloid: the stifling, web-like material that forms plaques in the brains of patients with Alzheimer’s disease, and also (more slowly) in everyone else’s, and impairs cognitive function."</ref>
# Extracellular crosslinks
+
# '''Extracellular crosslinks''': proteins binding together, impairing their functions<ref name="glycosens">[https://www.sens.org/our-research/intro-to-sens-research/glycosens/ "GlycoSENS"]. ''SENS Research Foundation''. "Crosslinks act like molecular 'handcuffs,' taking two neighboring proteins that were previously able to move independently of one another and binding them together, impairing their function in the same way that occurs to participants in a three-legged race."</ref>
# Cells resisting death
+
# '''Cells resisting death''': accumulated cells harmful in abundance (example: senescent cells)<ref name="apoptosens">[https://www.sens.org/our-research/intro-to-sens-research/apoptosens/ "ApoptoSENS"]. ''SENS Research Foundation''. "Pushing these cells to undergo such transformations is favored by evolution because it meets short-term needs, and having a few of these abnormal cells in the body for is nearly harmless. But the number of these cells in our tissues gradually rises over time, until by our fifth decade or so they begin to reach levels that are harmful to normal tissue function. [...] The original and most well-studied sort of cells of this type are what are usually called 'senescent' cells."</ref>
# Mitochondrial mutations
+
# '''Mitochondrial mutations''': harmful mtDNA variations due to waste from cellular energy conversion<ref name="mitosens">[https://www.sens.org/our-research/intro-to-sens-research/mitosens/ "MitoSENS"]. ''SENS Research Foundation''. "Just like real power plants, mitochondria generate toxic waste products in the process of 'burning' food energy as fuel – in this case, spewing out highly-reactive molecules called free radicals, which can damage cellular structures. [...] At worst, a free radical 'hit' to the mtDNA can cause major deletions in its genetic code, eliminating the mitochondria’s ability to use the instructions to make proteins that are critical components of their energy-generating system."</ref>
# Intracellular junk
+
# '''Intracellular junk''': breakdown-resistant molecules incapacitating cellular cleaning mechanisms<ref name="lysosens">[https://www.sens.org/our-research/intro-to-sens-research/lysosens/ "LysoSENS"]. ''SENS Research Foundation''. "Cells have a variety of systems for breaking down and recycling such unwanted materials, allowing them to clear garbage out of the way and reuse the raw materials. [...] However, sometimes these constituents are so badly fused together that not even the lysosome is able to tear them apart. And if something can’t be broken down in the lysosome, there’s nowhere else for it to go: it just stays there until either the lysosome disastrously ruptures, or the cell itself is destroyed."</ref>
# Nuclear mutations
+
# '''Nuclear mutations''': harmful DNA or epigenetic variations, especially cancer<ref name="oncosens">[https://www.sens.org/our-research/intro-to-sens-research/oncosens/ "OncoSENS"]. ''SENS Research Foundation''. "Mutations are damage to the DNA sequence itself, whereas epimutations are damage to the “scaffolding” of that DNA, which controls how and when genes get turned on in the cell. [...] The one that most people know about is cancer, which is the result of a series of (epi)mutations that happen in sequence in the cell, leading to its uncontrolled growth. Other kinds of (epi)mutations also occur in our cells over time, and some scientists have worried that these non-cancer-causing (epi)mutations might also contribute in different ways to age-related disease and disability. But there is good reason to believe that there aren’t enough such mutations to actually have a meaningful impact on our health."</ref>
  
 
== The Hallmarks of Aging ==
 
== The Hallmarks of Aging ==

Revision as of 12:31, 8 May 2021

Hallmarks of aging are distinctive features of the biological aging process. Such deteriorations have been enumerated with the goal of extending healthspan or lifespan: in Aubrey de Grey's Strategies for Engineered Negligible Senescence, and in the 2013 paper "The Hallmarks of Aging".

Strategies for Engineered Negligible Senescence

The Strategies for Engineered Negligible Senescence (SENS) are a classification of potential life extension therapies by the type of age-related damage they target. It was created by Aubrey de Grey in 2000 and published in his 2007 book Ending Aging. The seven types of damage listed are:

  1. Cell loss: fewer cells in tissue, causing deterioration, due to impaired dead-cell replacement by stem cells[1]
  2. Extracellular junk: old proteins (example: Alzheimer's plaque) impairing cell/tissue function[2]
  3. Extracellular crosslinks: proteins binding together, impairing their functions[3]
  4. Cells resisting death: accumulated cells harmful in abundance (example: senescent cells)[4]
  5. Mitochondrial mutations: harmful mtDNA variations due to waste from cellular energy conversion[5]
  6. Intracellular junk: breakdown-resistant molecules incapacitating cellular cleaning mechanisms[6]
  7. Nuclear mutations: harmful DNA or epigenetic variations, especially cancer[7]

The Hallmarks of Aging

"The Hallmarks of Aging" is a paper written by Carlos López-Otín, Maria Blasco, Linda Partridge, Manuel Serrano, and Guido Kroemer and published in 2013 in the journal Cell. The nine hallmarks presented are:

  1. Genomic instability
  2. Telomere attrition
  3. Epigenetic alteration
  4. Proteostasis loss
  5. Nutrient-sensing deregulation
  6. Mitochondrial dysfunction
  7. Cellular senescence
  8. Stem cell depletion
  9. Intercellular communication alteration

References

  • de Grey, Aubrey; Rae, Michael (2007). Ending Aging: The Rejuvenation Breakthroughs that Could Reverse Human Aging in Our Lifetime. ISBN 0-312-36706-6.
  • López-Otín, Carlos; Blasco, Maria A.; Partridge, Linda; Serrano, Manuel; Kroemer, Guido (6 June 2013). "The Hallmarks of Aging". Cell. 153 (6): 1194– 1217. doi:10.1016/j.cell.2013.05.039.

External links

  1. "RepleniSENS". SENS Research Foundation. "Some of these damaged cells are repaired, but others are either destroyed, or forced into a dysfunctional ‘senescent’ state where they can no longer divide, or commit ‘cellular suicide’ (apoptosis) for the greater good of the body. Some of the lost cells are replaced by the pools of specialized, tissue-specific stem cells, but the degenerative aging process makes these stem cell pools less effective at repair over time."
  2. "AmyloSENS". SENS Research Foundation. "Extracellular junk is accumulations of sticky, malformed proteins that no longer serve their function, but instead impair cell or tissue function by their presence. [...] The most well-known form of extracellular junk is beta-amyloid: the stifling, web-like material that forms plaques in the brains of patients with Alzheimer’s disease, and also (more slowly) in everyone else’s, and impairs cognitive function."
  3. "GlycoSENS". SENS Research Foundation. "Crosslinks act like molecular 'handcuffs,' taking two neighboring proteins that were previously able to move independently of one another and binding them together, impairing their function in the same way that occurs to participants in a three-legged race."
  4. "ApoptoSENS". SENS Research Foundation. "Pushing these cells to undergo such transformations is favored by evolution because it meets short-term needs, and having a few of these abnormal cells in the body for is nearly harmless. But the number of these cells in our tissues gradually rises over time, until by our fifth decade or so they begin to reach levels that are harmful to normal tissue function. [...] The original and most well-studied sort of cells of this type are what are usually called 'senescent' cells."
  5. "MitoSENS". SENS Research Foundation. "Just like real power plants, mitochondria generate toxic waste products in the process of 'burning' food energy as fuel – in this case, spewing out highly-reactive molecules called free radicals, which can damage cellular structures. [...] At worst, a free radical 'hit' to the mtDNA can cause major deletions in its genetic code, eliminating the mitochondria’s ability to use the instructions to make proteins that are critical components of their energy-generating system."
  6. "LysoSENS". SENS Research Foundation. "Cells have a variety of systems for breaking down and recycling such unwanted materials, allowing them to clear garbage out of the way and reuse the raw materials. [...] However, sometimes these constituents are so badly fused together that not even the lysosome is able to tear them apart. And if something can’t be broken down in the lysosome, there’s nowhere else for it to go: it just stays there until either the lysosome disastrously ruptures, or the cell itself is destroyed."
  7. "OncoSENS". SENS Research Foundation. "Mutations are damage to the DNA sequence itself, whereas epimutations are damage to the “scaffolding” of that DNA, which controls how and when genes get turned on in the cell. [...] The one that most people know about is cancer, which is the result of a series of (epi)mutations that happen in sequence in the cell, leading to its uncontrolled growth. Other kinds of (epi)mutations also occur in our cells over time, and some scientists have worried that these non-cancer-causing (epi)mutations might also contribute in different ways to age-related disease and disability. But there is good reason to believe that there aren’t enough such mutations to actually have a meaningful impact on our health."