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Comment by florin on Why SENS makes sense · 2020-02-28T23:43:35.805Z · score: 1 (1 votes) · EA · GW

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.

Comment by florin on Why SENS makes sense · 2020-02-28T20:11:24.900Z · score: 1 (1 votes) · EA · GW

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.

Comment by florin on Why SENS makes sense · 2020-02-27T21:31:40.945Z · score: 1 (1 votes) · EA · GW

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."

Comment by florin on Why SENS makes sense · 2020-02-26T22:54:16.196Z · score: 1 (1 votes) · EA · GW

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.

Comment by florin on Why SENS makes sense · 2020-02-25T07:03:12.015Z · score: 2 (2 votes) · EA · GW

I'd like to point out a few things.

1) The key reason why SENS makes the most sense as a way to cure aging is that—as with any physical system—structure determines function; by repairing damage that accumulates in the body's molecular and cellular structures, the normal, disease-free functioning of the body should also be restored.

2) A more detailed version of the SENS roadmap is available at SENS' original website.

3) You've miscategorized some of the SRF's projects.

4) SENS and Hallmarks aren't as similar as they first appear. Sometimes, there's no overlap between SENS and Hallmarks. And unlike SENS, Hallmarks advocates lots of messing with metabolism.

5) Human Bio never took off and now Repair Biotechnologies has replaced it.

6) SRF publications are available here.