4 ms·

> “By pinpointing AP-1 as a master controller linked to aging across cell types, we can now study the effects of drugs that reduce its activity to extend qualit

> “By pinpointing AP-1 as a master controller linked to aging across cell types, we can now study the effects of drugs that reduce its activity to extend quality of life,” he said [2]. Targeting AP-1 and its associated pathways could lead to interventions that slow down or even prevent the onset of these diseases, marking a significant advancement in geriatric medicine. Unfortunately, AP-1 is also involved in cancer. From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361657/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361657/ > Activator protein-1 (AP-1) is a transcription factor that consists of a diverse group of members including Jun, Fos, Maf, and ATF. AP-1 involves a number of processes such as proliferation, migration, and invasion in cells. Dysfunctional AP-1 activity is associated with cancer initiation, development, invasion, migration and drug resistance. Mentioning AP-1 without mentioning its role in cancer is misleading. Many of the mechanisms that are involved with aging, likely have a role with controlling cancer by keeping cells, especially cells with damage, from proliferating or invading nearby or distant tissue.

CuriouslyC 2y ago
True, but we're getting a lot better at treating cancer, so I suspect that it is going to end up that we try to target it semi-selectively for life extension with the knowledge that it may cause cancer, then try to treat any cancers that emerge.
- aflag 2y ago
  We're still terrible at treating cancer though. And the treatments very likely cause other health issues that can actually reduce life expectancy.
  - fzeroracer 2y ago
    We've massively improved in cancer treatment in just the past 20 years alone. Every year we get more and more precise with our ability to both map and target tumors, which in turn means less damage to the body as a whole during treatment and better odds of tumor elimination. This goes for both chemo and radiation.
- Tade0 2y ago
  You'd need a particularly good (and cheap!) screening method to catch them before they become fatal. Digestive tract cancers in particular are often confused by patients with other, benign issues and are therefore diagnosed too late.
  - toomuchtodo 2y ago
    https://grail.com/ https://grail.com/ seems like the path we're on for that sort of screening (blood borne cancer biomarker surveillance)? AP-1 tweaks + mRNA and immunotherapy protocols for detected cancer + continued cancer screening developments might be a material longevity improvement. Typically, you're trying to die before any cancer gets you long term, so the need is to continually improve cancer detection and treatment. https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment https://www.cancer.gov/about-cancer/treatment/types/biomarke... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074993/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074993/
- gumby 2y ago
  > we're getting a lot better at treating cancer, Is this really true? I know we are getting better in diagnosing cancers, so the time from initial diagnosis to death is longer, but it's not clear that overall lifespan of people with all cancers is any longer. If anything, because treatment starts sooner, quality of life may have diminshed. It is definitely true that treatments for some cancers have improved over the last couple of decades. I find the immunotherapies particularly exciting and seemingly promising. But in the broader cases I am not sure I could agree with your statement.
  - jagger27 2y ago
    Early detection when treatment is easier is better treatment.
    - cellularmitosis 2y ago
      They asked “are we decreasing the slope of this graph” and you replied by pointing to the graph and saying “if you choose a lower value of x, you get a lower value of y”. That’s good news, but that’s not what they asked.
      - jagger27 2y ago
        But early treatment does lead to better longterm outcomes for a whole bunch of cancers, so I take issue with your facile reply. A mole removal with local anesthetic by your local dermatologist will almost always lead to better outcomes than two rounds of surgery, chemo, and radiation to treat stage 4 metastatic melanoma.
        cellularmitosis 2y ago
        Yes, of course! As I said, that’s good news.
  - kortilla 2y ago
    Remission rates are higher the earlier you catch it
- overstay8930 2y ago
  Cancer treatment is still objectively primitive, unless you catch it early it still mostly boils down to balancing keeping you barely alive and hoping the cancer dies first. Cancer survival rate has gone up because of treatment accessibility and testing, not because of any major breakthroughs.
futureshock 2y ago
I have often heard it said that if we found a cure for cancer we would also get a cure for aging. The one immortal human I know is Henrietta Lacks (or her cancer rather).
- jonathanlydall 2y ago
  Fascinating. https://en.wikipedia.org/wiki/Henrietta_Lacks https://en.wikipedia.org/wiki/Henrietta_Lacks
  - evanmoran 2y ago
    Amazingly, her immortal cell line was instrumental in polio eradication! https://en.wikipedia.org/wiki/HeLa#Polio_eradication https://en.wikipedia.org/wiki/HeLa#Polio_eradication
- onlyrealcuzzo 2y ago
  I have heard that we age, primarily, to prevent ourselves from dying of cancer even faster than we already do. Animals that don't really age like the lobster, giant tortoise, bowhead whale, elephant, etc - also get cancer much less than we do.
  - jacobn 2y ago
    Is it known why/how those animals have reduced / negligible senescence? Like do they have some other variant of the AP-1 gene(s), or some such?
    - sterlind 2y ago
      one factor is how many copies of the p53 tumor suppressor gene they have. larger animals (with more cells) tend to have more copies of p53. p53 causes cells to self-destruct if they go off-script. many cancers have p53 mutations to thwart this. iirc senescence blocks damaged (potentially pre-cancerous) cells from reproducing, but unlike p53 doesn't kill them. replacing sensescent cells means more cell divisions, which also risks a cancerous mutation. so reducing senescence probably means making p53 more sensitive and redundant.

CuriouslyC 2y ago

True, but we're getting a lot better at treating cancer, so I suspect that it is going to end up that we try to target it semi-selectively for life extension with the knowledge that it may cause cancer, then try to treat any cancers that emerge.

aflag 2y ago
We're still terrible at treating cancer though. And the treatments very likely cause other health issues that can actually reduce life expectancy.
- fzeroracer 2y ago
  We've massively improved in cancer treatment in just the past 20 years alone. Every year we get more and more precise with our ability to both map and target tumors, which in turn means less damage to the body as a whole during treatment and better odds of tumor elimination. This goes for both chemo and radiation.
Tade0 2y ago
You'd need a particularly good (and cheap!) screening method to catch them before they become fatal. Digestive tract cancers in particular are often confused by patients with other, benign issues and are therefore diagnosed too late.
- toomuchtodo 2y ago
  https://grail.com/ https://grail.com/ seems like the path we're on for that sort of screening (blood borne cancer biomarker surveillance)? AP-1 tweaks + mRNA and immunotherapy protocols for detected cancer + continued cancer screening developments might be a material longevity improvement. Typically, you're trying to die before any cancer gets you long term, so the need is to continually improve cancer detection and treatment. https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment https://www.cancer.gov/about-cancer/treatment/types/biomarke... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074993/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074993/
gumby 2y ago
> we're getting a lot better at treating cancer, Is this really true? I know we are getting better in diagnosing cancers, so the time from initial diagnosis to death is longer, but it's not clear that overall lifespan of people with all cancers is any longer. If anything, because treatment starts sooner, quality of life may have diminshed. It is definitely true that treatments for some cancers have improved over the last couple of decades. I find the immunotherapies particularly exciting and seemingly promising. But in the broader cases I am not sure I could agree with your statement.
- jagger27 2y ago
  Early detection when treatment is easier is better treatment.
  - cellularmitosis 2y ago
    They asked “are we decreasing the slope of this graph” and you replied by pointing to the graph and saying “if you choose a lower value of x, you get a lower value of y”. That’s good news, but that’s not what they asked.
    - jagger27 2y ago
      But early treatment does lead to better longterm outcomes for a whole bunch of cancers, so I take issue with your facile reply. A mole removal with local anesthetic by your local dermatologist will almost always lead to better outcomes than two rounds of surgery, chemo, and radiation to treat stage 4 metastatic melanoma.
      - cellularmitosis 2y ago
        Yes, of course! As I said, that’s good news.
- kortilla 2y ago
  Remission rates are higher the earlier you catch it
overstay8930 2y ago
Cancer treatment is still objectively primitive, unless you catch it early it still mostly boils down to balancing keeping you barely alive and hoping the cancer dies first. Cancer survival rate has gone up because of treatment accessibility and testing, not because of any major breakthroughs.

futureshock 2y ago

I have often heard it said that if we found a cure for cancer we would also get a cure for aging. The one immortal human I know is Henrietta Lacks (or her cancer rather).

jonathanlydall 2y ago
Fascinating. https://en.wikipedia.org/wiki/Henrietta_Lacks https://en.wikipedia.org/wiki/Henrietta_Lacks
- evanmoran 2y ago
  Amazingly, her immortal cell line was instrumental in polio eradication! https://en.wikipedia.org/wiki/HeLa#Polio_eradication https://en.wikipedia.org/wiki/HeLa#Polio_eradication
onlyrealcuzzo 2y ago
I have heard that we age, primarily, to prevent ourselves from dying of cancer even faster than we already do. Animals that don't really age like the lobster, giant tortoise, bowhead whale, elephant, etc - also get cancer much less than we do.
- jacobn 2y ago
  Is it known why/how those animals have reduced / negligible senescence? Like do they have some other variant of the AP-1 gene(s), or some such?
  - sterlind 2y ago
    one factor is how many copies of the p53 tumor suppressor gene they have. larger animals (with more cells) tend to have more copies of p53. p53 causes cells to self-destruct if they go off-script. many cancers have p53 mutations to thwart this. iirc senescence blocks damaged (potentially pre-cancerous) cells from reproducing, but unlike p53 doesn't kill them. replacing sensescent cells means more cell divisions, which also risks a cancerous mutation. so reducing senescence probably means making p53 more sensitive and redundant.