3) If you point out what categories I got wrong and why, I can correct if needed.
4) It seems to me that the biggest point of difference is the genomic instability hallmark, which is not present in SENS because de Grey believes it acts more slowly and probably belongs to a “SENS 2” panel of therapies. The others either mostly overlap or they are closely causally related. Do you agree?
Well, it’s complicated. Hallmarks is missing crosslinks, intracellular junk like lipofuscin and lipids like 7KC, and damaged elastin. SENS is partly missing genomic instability at least in SENS 1.0 (as you’ve mentioned), but it does include mitochondrial mutations which Hallmarks considers to be one aspect of genomic instability and mentions cancer as a consequence of nuclear mutations which are another aspect of genomic instability. SENS is also missing epigenetic alterations but might consider them for SENS 2.0. SENS doesn’t consider telomere attrition as a significant type of damage, and in fact, SENS advocates removing the ability of all cells to extend their telomeres as a strategy to prevent cancer. Besides the differences regarding aging damage, the most crucial difference between SENS and Hallmarks is that most of the interventions that Hallmarks mentions won’t help out that much in reaching LEV.
Now, it should be even easier to figure out how to correct those miscategorizations.
SENS doesn’t consider telomere attrition as a significant type of damage, and in fact, SENS advocates removing the ability of all cells to extend their telomeres as a strategy to prevent cancer.
I think SENS doesn’t consider telomere attrition because the solution would be the same as the one for cell loss (and telomere attrition is a direct cause of cell loss). Also note that at SRF they consider the strategy against cancer less and less likely to be necessary (and I hope so, since it is the most far fetched and difficult).
Besides the cancer thing, SENS ignores telomere attrition, because it’s still unclear if telomere attrition is a significant cause of aging. And the likelihood that WILT will be needed is still above 50%.
Besides the cancer thing, SENS ignores telomere attrition, because it’s still unclear if telomere attrition is a significant cause of aging. And the likelihood that WILT will be needed is still above 50%.
Isn’t early detection of cancer (and intervention) more feasible?
Can you think of any other intervention that has a good theoretical chance to eliminate all cancer?
Besides WILT, the only other intervention I can think of that might provide a complete cancer cure are the leukocytes used in Cui’s cancer-proof mice experiments, but it’s not known whether all types of cancer can be eliminated by these immune cells. Fortunately, LIfT BioSciences is planning to start a clinical trial in 2022 using this approach.
The proteins that the proteostasis hallmark talks about refers to proteins like beta-amyloid and tau that misfold and subsequently form aggregates. Proteins that are crosslinked aren’t misfolded but rather they become “glued” together by a chemical reaction and don’t form aggregates. 7-KC isn’t a protein and doesn’t misfold; it’s an oxidized lipid.
Edited my comment slightly before yours appeared. Wanted to specify the reasons more but resolved to delete them since I was going to modify the post anyway. The rationale was that 7-KC, even if not a protein, is still an aggregate that overwhelms lysosomes and actively causes their dysfunction (loss of function of lysosomes and other degradation mechanisms being accounted for in the loss of proteostasis paragraphs in the Hallmarks).
If you still feel unsure about the 7-KC thing, the following reasons should put your doubts to rest:
1) Although 7-KC accumulates, it doesn’t aggregate.
2) If Hallmarks really thought that lipid accumulation belonged to the proteostasis hallmark it would have said so.
3) Hallmarks completely ignores 7-KC as a causative factor of atherosclerosis and instead ties atherosclerosis to “uncontrolled cellular overgrowth or hyperactivity” which is nonSENSical.
3) If you point out what categories I got wrong and why, I can correct if needed.
4) It seems to me that the biggest point of difference is the genomic instability hallmark, which is not present in SENS because de Grey believes it acts more slowly and probably belongs to a “SENS 2” panel of therapies. The others either mostly overlap or they are closely causally related. Do you agree?
Well, it’s complicated. Hallmarks is missing crosslinks, intracellular junk like lipofuscin and lipids like 7KC, and damaged elastin. SENS is partly missing genomic instability at least in SENS 1.0 (as you’ve mentioned), but it does include mitochondrial mutations which Hallmarks considers to be one aspect of genomic instability and mentions cancer as a consequence of nuclear mutations which are another aspect of genomic instability. SENS is also missing epigenetic alterations but might consider them for SENS 2.0. SENS doesn’t consider telomere attrition as a significant type of damage, and in fact, SENS advocates removing the ability of all cells to extend their telomeres as a strategy to prevent cancer. Besides the differences regarding aging damage, the most crucial difference between SENS and Hallmarks is that most of the interventions that Hallmarks mentions won’t help out that much in reaching LEV.
Now, it should be even easier to figure out how to correct those miscategorizations.
I think SENS doesn’t consider telomere attrition because the solution would be the same as the one for cell loss (and telomere attrition is a direct cause of cell loss). Also note that at SRF they consider the strategy against cancer less and less likely to be necessary (and I hope so, since it is the most far fetched and difficult).
Edit: categorization mistakes corrected :)
Besides the cancer thing, SENS ignores telomere attrition, because it’s still unclear if telomere attrition is a significant cause of aging. And the likelihood that WILT will be needed is still above 50%.
The miscategorizations have only been partially corrected. 7-KC isn’t related to Hallmarks, and the crosslink projects should be classified as “extracellular crosslinks” or “extracellular matrix stiffening.”
Isn’t early detection of cancer (and intervention) more feasible?
Can you think of any other intervention that has a good theoretical chance to eliminate all cancer?
Besides WILT, the only other intervention I can think of that might provide a complete cancer cure are the leukocytes used in Cui’s cancer-proof mice experiments, but it’s not known whether all types of cancer can be eliminated by these immune cells. Fortunately, LIfT BioSciences is planning to start a clinical trial in 2022 using this approach.
Yep, seems like for some reason I, err… aggregated extracellular matrix stiffening and extracellular aggregates together. Mistake corrected.
The proteins that the proteostasis hallmark talks about refers to proteins like beta-amyloid and tau that misfold and subsequently form aggregates. Proteins that are crosslinked aren’t misfolded but rather they become “glued” together by a chemical reaction and don’t form aggregates. 7-KC isn’t a protein and doesn’t misfold; it’s an oxidized lipid.
Edited my comment slightly before yours appeared. Wanted to specify the reasons more but resolved to delete them since I was going to modify the post anyway. The rationale was that 7-KC, even if not a protein, is still an aggregate that overwhelms lysosomes and actively causes their dysfunction (loss of function of lysosomes and other degradation mechanisms being accounted for in the loss of proteostasis paragraphs in the Hallmarks).
If you still feel unsure about the 7-KC thing, the following reasons should put your doubts to rest:
1) Although 7-KC accumulates, it doesn’t aggregate.
2) If Hallmarks really thought that lipid accumulation belonged to the proteostasis hallmark it would have said so.
3) Hallmarks completely ignores 7-KC as a causative factor of atherosclerosis and instead ties atherosclerosis to “uncontrolled cellular overgrowth or hyperactivity” which is nonSENSical.