Comment by jbandela1 | Hacker News Reader

Comment by jbandela1 | Hacker News Reader

> “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/

> 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.

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).

Fascinating.

https://en.wikipedia.org/wiki/Henrietta_Lacks

Amazingly, her immortal cell line was instrumental in polio eradication! https://en.wikipedia.org/wiki/HeLa#Polio_eradication

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.

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?

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.

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.

We're still terrible at treating cancer though. And the treatments very likely cause other health issues that can actually reduce life expectancy.

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.

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.

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/biomarke...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074993/

> 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.

Early detection when treatment is easier is better treatment.

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.

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.

Yes, of course! As I said, that’s good news.

Remission rates are higher the earlier you catch it

Yes, having just gone through this i was surprised to find that cancer of almost all kinds is rapidly becoming more manageable. Prognosis is quite good for most people and most cancers when caught early enough.

It is still an artform though and procedures that lead to a long healthy life in a majority of patients still cause deaths in some others.

Progress in treatment isn't uniform across all cancers, but yes we are getting a lot better at it.

Hope you are doing well, and wishing you the very best.

Your comment answers itself. There is no such thing as "cancer, singular". It's a catch-all term for a wide range of conditions relating to uncontrolled tissue growth.

We have gotten a lot better at treating cancer, in general, literally because we've gotten a lot better at treating specific types of cancer. There are no "broader cases", only cases of specific cancers which we've either gotten really good at treating, or which we haven't gotten really good at treating yet.

It is true. Stage 3 used to be a death sentence in early 1990s. It is survivable now for most kinds of cancer.

It is a really fair question, and I do not think it is totally clear cut. There are some cancers which are significantly more treatable than previously, but the numbers are also getting juiced from other directions.

We are detecting cancers earlier than before. Which can mean that, without any change in treatment efficacy, people are "surviving longer" with the disease. Another biggie is that people are smoking significantly less than 20+ years ago (both smokers and secondary exposure). While we are continually finding new ways to slowly poison ourselves (eg PFAS), we have also reduced exposure to other environmental toxins: lead paint/gas, DDT, etc,

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.

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