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Comment by danieltillett | Hacker News Reader

All of these approaches are going to run into the reason why ageing is happening in the first place - to prevent cancer. Ageing is one of the original anti-oncogenic systems and anything that messes with the rate of aging without doing something about cancer is doomed to failure.

Interesting there are some human mutations that slow down the ageing rate [1]. These all cause an increased cancer rate, but if you manage to make it to old age you are physiologically much younger (20-30 years in the case of the Brazilian p53 mutation).

1. https://www.ncbi.nlm.nih.gov/pubmed/27663983

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>"if you manage to make it to old age you are physiologically much younger (20-30 years in the case of the Brazilian p53 mutation)."

That sounds interesting, but I can't find it. Can you quote the part of that paper you are talking about?

Have a look at this NIH talk [1].

1. https://youtu.be/URKJ7LLXc3E

Are you saying that info was not in your original source? I'm not willing to spend 15 minutes watching a video to possibly get this info. I have low hopes since the speaker probably cannot cite their source in that format. Can you tell me what minute of the video I should watch?

The reference I provided was to the mutation, not the anti-ageing phenotype.

The speaker is one of the PI’s on the project so it is worth watching the whole thing. I can’t find the paper again where the delayed ageing is mentioned, but the speaker does talk about it - far more offhand than it should be for my liking.

It is pretty easy to ff through a scientific talk because of the slides, but if you are just interested in the Brazilian mutation then start from around 6 minutes.

Which is why the SENS portfolio includes a universal cure for cancer.

This is not as hard as people have been made to think it is. The present mainstream approach of the past few decades is just not a good one. It is picking strategies that are very expensive to implement, and that attack vulnerabilities that are peculiar to tiny subtypes of cancer. There are hundreds of subtypes of cancer, most of which are cheerfully capable of evolving their way around many of the existing attacks on their biochemical vulnerabilities. There are only so many scientists, only so much funding. If it takes twenty man-years to produce a therapy to tackle transient vulnerability A in subtype 1 of 1000, we'll never see the end of it. Yet this is largely what is happening.

What should be happening instead is the whole-hearted pursuit of vulnerabilities that are common to many, many types of cancer, or all cancers for preference.

There is one very good one, which is that cancers must lengthen their telomeres, and there are only two ways for that to happen, neither of which should really be operating in somatic cells. So block telomerase, block ALT, and get that hooked up to some kind of cancer-cell-targeting-mechanism of the sort that has been under development for the past decade, and that will work to kill any cancer. A number of high profile groups are working on telomerase sabotage ( https://www.eurekalert.org/pub_releases/2015-01/usmc-rtt1231... ), and the SENS Research Foundation has been funding the necessary research to address ALT ( http://www.sens.org/research/introduction-to-sens-research/c... ), still at comparatively early stages.

There are other, prospective targets. The comparative biology crowd is reverse engineering naked mole rats to figure out what it is that makes them next to immune to cancer. There are a few leads there; p21, ARF, hyaluronan, alpha2-macroglobulin, etc. Another recent discovery relates to re-engaging the limitation on processing nutrients; apparently all cells have a food limiter, and all cancers abuse that limiter in order to enable rampant replication. Re-enable the limiter and cancers wither: https://www.salk.edu/news-release/salk-scientists-curb-growt...

So there is no shortage of possibilities for people who want to kill all cancer. There is no excuse for continuing the wasteful business as usual of the past decades. This is an age of revolutionary progress in biotechnology - we should act like it and aim high.

>"there is no shortage of possibilities for people who want to kill all cancer."

Your posts in this thread make me think you have a different view of what is going on regarding aging and cancer than I do...

As mentioned below, it seems that after each division more and more "genetic errors and other junk" accumulate in tissue stem cells. After a certain number of these divisions the stem cell needs to stop replenishing the tissue because the risk of generating a cancer cell is too high. Thus the turnover of terminal cells must slow and eventually stop as each tissue stem cell becomes "exhausted".

So the options upon exhaustion (of safe divisions) of the stem cells are either:

1) Continue replenishing the tissue at a high risk of cancer. Even the non-tumorgenic new terminal cells are also becoming less and less functional due to the accumulated erros/junk.

- high cancer risk, slow organ failure

2) Stop replenishing the tissue and let whatever cells are there survive as long as possible (these are the senescent cells).

- low cancer risk, slow/intermediate rate organ failure

3) Stop replenishing the tissue and remove the senescent cells, replacing the space with connective tissue. In this case the tissue will become less and less functional eventually leading to organ failure.

- low cancer risk, fast organ failure

All of your ideas proposed here seem to be #1 or #3. Nature's solution is #2, and probably for good reason.

Also, obviously the ultimate solution needs to be either reducing the number of cell divisions or the rate of junk/error accumulation per division. This all seems to follow very easily from the premise that errors/junk accumulate after each division, so I would be interested to know what you are reading that makes you think it is incorrect.

The other solution is as suggested which is increase the robustness of the anti-oncogene systems. This way the stem cells will still accumulate mutations (hard to solve this problem), but they won’t progress to cancer.

This approach is how evolution has solved the problem of cancer in large animals with long lifespans.

What do you mean by "anti-oncogene systems? That makes me think of stuff like this: https://en.wikipedia.org/wiki/Tumor_suppressor_gene#Function...

Those functions are pretty much the same as what I mentioned above (adhesion isn't included in my list):

"obviously the ultimate solution needs to be either reducing the number of cell divisions or the rate of junk/error accumulation per division"

Tumor suppressor is a synonym for anti-oncogene. The systems present in each species is not the same and the large long lived animals of more and better systems. Unfortunately, we don't know too much about them.

That is called Peto's paradox: https://en.wikipedia.org/wiki/Peto%27s_paradox. Afaik the idea that larger animals have more robust tumor suppression systems is an assumption required due to a possibly incorrect understanding of the stem cell division scheme: https://www.ncbi.nlm.nih.gov/pubmed/25459141

If you look close enough at this topic you will realize that we don't have good data on how many divisions are actually happening in each tissue. Our understanding is very rudimentary so it is extremely dangerous to take anything as fact on this topic. As a science, cancer research is not even yet at the point of astronomy when people began estimating the number of stars...

It is in a pre-astrology stage where all sorts of wild speculations and fads reign supreme.

EDIT:

Note that in the Morris 2014 paper I linked he calls Peto's paradox the "man-mouse paradox" and uses 'Peto's paradox' to mean something else.

We actually know that elephants have extra systems for controlling cancer and we haven't really looked carefully [1]. We have also learned a little about these systems in bowhead whales [2].

I think we are a bit further along with understanding cancer (we haven't found a major oncogene in a while), but I do agree we still have a way to go, especially on the treatment/prevention front.

1. https://www.nature.com/news/how-elephants-avoid-cancer-1.185...

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536333/

This is still wild speculation. "Elephants live a long time and have multiple copies of p53" (these retrotransposed copies so they are under different promoters, missing introns, etc ...) does not equate to what you said. Look at all the functions for p53 on the right of this page: https://en.wikipedia.org/wiki/TP53

It is not difficult at all to look at a genome and find some pattern that you can weave a plausible story around.

Also, here are the conclusions of your two papers:

>"To our knowledge, this study offers the first supporting evidence based on empirical data that larger animals with longer life spans may develop less cancer, especially elephants.

[...]

Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53."

>"The genetic and molecular mechanisms by which longevity evolves remain largely unexplained"

Now consider how simplistic the idea behind these studies is: "Elephants/whales live a long time and are rarely observed to get cancer relative to humans, we should look into why". Investigation of the most basic aspects of the problem has only begun a few years ago...

What we really need is to look at is elephants and bowhead whales in detail. These animals have a large number of extra anti-oncogene systems that prevent them getting cancer despite their large size and long life span.

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