
As we age, cancer rates go up as immune system winds down - okket
https://arstechnica.com/science/2018/02/as-we-age-cancer-rates-go-up-as-immune-system-winds-down/#p3
======
ransom1538
I always think of these two monkeys[i] when I consider slowing down my age.

[i]
[http://www.slate.com/articles/health_and_science/medical_exa...](http://www.slate.com/articles/health_and_science/medical_examiner/2012/08/calorie_restriction_and_longevity_monkey_study_shows_hunger_doesn_t_increase_longevity_but_type_of_food_does_.html)

~~~
mysterypie
It's an interesting well-written article, but you realize that their main
point was that it contradicts the earlier calorie-restriction study: _" The
Nature authors found no increase in lifespan; the calorically restricted
animals lived no longer, statistically, than their well-fed cousins."_

They try to reconcile the studies: maybe it's the natural-ingredient foods vs
the refined foods, maybe it's the generous diet vs the more-than-generous
free-feeding, or conceding that the monkey's don't live longer, but they live
healthier.

IMO, the best paragraph from the article was this: _" Many of us simply roll
our eyes and click away when yet another medical study contradicts the last
study—so what else is new? Coffee’s bad for you, until it’s good for you—and
so is red wine. Antioxidants are essential, or they’re useless. And so on."_

Other than some very basic common sense things -- like don't eat rat poison --
I never find that these kinds of studies lead to _correct_ and _actionable_
information about how to slow down aging or how to lead your life. And it's
extremely frustrating to even try.

~~~
yongelee
To even try? To try to exercise and not drink sodas is extremely frustrating?
Living a healthy lifestyle is about simple choices like going to the gym or
adding broccoli to your meal and avoiding junk food.

~~~
mysterypie
> To even try?

Sorry, I should have been clearer. I meant, to even try to keep up with the
contradictory medical studies.

Yes, you should exercise; that's a common sense thing I'm referring to. But
trying to decide if things like calorie restriction really work in the face of
conflicting studies is frustrating.

~~~
mjlangiii
nutritionfacts.org was created for this reason, to consolidate the evidence
from nutritional studies so that you don't have to.

spoiler alert - the comprehensive review lead them to the conclusion to eat
plants, unprocessed.

But anyway, it is a nice resource to get a round up of studies on a similar
topic.

~~~
throwpupper
nutritionfacts.org is an extremely biased site that has been created by a
vegan who built his whole career on speaking about health issues. While it has
the word "facts" in its title nothing prevents them from cherry-picking
studies to support their original views.

If you cherry-pick different studies you might actually find that consuming
large amount of plants stresses our digestive system way more than a fatty
steak with potatoes.

~~~
cies
> If you cherry-pick different studies you might actually find that consuming
> large amount of plants stresses our digestive system way more than a fatty
> steak with potatoes.

You really, REALLY, believe with all information being out there nowadays that
a diet of only "fatty steak with potatoes" will be healthier for humans that
the "balanced WFPB diet" that is nutritionfacts.org claims is scientifically
proven to be the healthiest?

I think you have nothing to back that up. Please cherry pick how you please
and present your evidence.

Dr Greger, who started the non-profit nutritionfacts.org, is often attacked
for being an ethical vegan. Since people reason that would impair his ability
to present unbiased evidence. Though no-one has ever gotten beyond claiming
he's cherry picking. I wish someone would describe a different diet that is as
well supported by scientific evidence, as what nutritionfacts is doing for
WFPB.

There is some scientific evidence building up in for the Keto diet. But that
is --as far as I know-- not a diet for life.

On the other hand there is the raw diet movement (basically an uncooked WFPB
diet), but that has little scientific and mostly anecdotal evidence.

~~~
debacle
The keto diet's main difficulties are the prevalence and preponderance of
available sugary foods, the near inability to eat socially, and the extreme
difficulty in adopting the diet in the first 3 weeks for people regularly
consuming 200g+ of carbohydrates a day.

The raw diet is mostly a trendy thing people write about. The bioavailability
of nutrients in many raw foods is just too meh.

We know what the best diet is. A plant and fish based diet with small amounts
of other meat. Meat that doesn't subsist on a diet primarily of corn or other,
less edible things. This diet is completely unsustainable on a global scale
and would result in even more ecological havoc.

The discussion between plants or plants + meat is complicated, but for now I'm
going to ignore it because there's more important considerations:

\- Companies are making our produce harder to digest as they try and make
products with a longer shelf life.

\- Eating industrially produced meat (of any sort) is very unhealthy and in
many ways unsafe.

\- This entire discussion removes dairy from the equation, which is a large
part of the puzzle for most people.

\- The low-carb vegan and the low-carb omnivore are far better off than anyone
consuming 200g+ of carbohydrates a day.

\- Hydroponically grown carrots taste gross.

~~~
cies
> We know what the best diet is. A plant and fish based diet with small
> amounts of other meat.

Nope. Fish (most fish) as a central part of diet, will contribute a lot to
build up of heavy metals in humans. And what is "small amounts of other meat"?
3x per week? This is basically an omnivorous diet. Compared to the SAD is
probably just the junk cut out.

This, SAD-processed, is a very unhealthy diet, compared to a balanced WFPB
diet. There are lots of studies to back this up.

> \- Companies are making our produce harder to digest as they try and make
> products with a longer shelf life.

Yups.

> \- Eating industrially produced meat (of any sort) is very unhealthy and in
> many ways unsafe.

Not a problem for those eating WFPB.

> \- This entire discussion removes dairy from the equation, which is a large
> part of the puzzle for most people.

Dairy is a killer. Prolly more so than meat.

[https://www.youtube.com/watch?v=h3c_D0s391Q](https://www.youtube.com/watch?v=h3c_D0s391Q)

> \- The low-carb vegan and the low-carb omnivore are far better off than
> anyone consuming 200g+ of carbohydrates a day.

Any study on this?

There is a lot of studies (long running, with large size populations) claiming
the opposite. Here some arguments: [http://www.masteringdiabetes.org/ketosis-
ketogenic-diets-mis...](http://www.masteringdiabetes.org/ketosis-ketogenic-
diets-misleading/)

> \- Hydroponically grown carrots taste gross.

Personal taste. It prolly has less phytonutrients. Not sure how this is an
important consideration.

~~~
debacle
The site you linked is thick which propaganda which makes me doubt your bias
and arguments. Choosing your sources is important for making a compelling
argument.

~~~
cies
One man's truth is another's propaganda, what are your sources? (I've shown
mine, and I must say it's pretty convincing and lines up with what I already
knew about the human body)

I'm not at all saying there's no use for keto, I just think it should never be
a mainstream diet (but something applied in specific cases, under medical
supervision). As far as sci evidence goes, WFPB seems to be the "best" diet
for the human species as a whole.

------
lisper
One immediate problem with the hypothesis that cancer is caused by the loss of
T cells with age is the fact that HIV also destroys T cells, and it is
associated with increased risk of some types of cancer. But the cancers
associated with HIV are _different_ from those associated with aging. In
particular, Kaposi sarcoma occurs 500 times more in HIV patients than the
general population. So there must be something else going on besides just the
loss of T cells.

~~~
cma
Kaposi sarcoma is associated with Kaposi's sarcoma-associated herpesvirus even
in the HIV cases though. It might be that losing the amount of T cells you
lose with HIV or immunosuppression has a different effect than just losing
some fraction of them with age with respect to that virus.

------
kazinator
The link between cancer and the immune system (the latter's role in defending
against the former) is not all that clear.

Here is a cancer.com (American Cancer Society) article on the relationship
between AIDS and cancer.

Source: [https://www.cancer.org/cancer/cancer-causes/infectious-
agent...](https://www.cancer.org/cancer/cancer-causes/infectious-agents/hiv-
infection-aids/hiv-aids-and-cancer.html)

Firstly, they say that _" In fact, some types of cancer occur so often in
people with AIDS that they are considered AIDS-defining conditions"_.

But that's only certain specific cancers. Then there are some other cancers
that occur often with AIDS but are not "AIDS-defining".

And then there is the kicker: _" Of course, as people with HIV are now living
longer, they are also developing other cancers that are not clearly linked to
HIV but are more common in older people, such as breast, colorectal, and
prostate cancer."_.

So, these cancers go up in AIDS survivors due to age, even though those people
have immune systems that were already shot years before.

So much for a tidy hypothesis about aging -> lower immune system -> cancer, I
suppose.

As for why those afflicted with AIDS get certain cancers, one explanation
(also given in above page) is that some cancers are caused by viral
infections. Weakened defense against viral infections, increased cancer of
that type.

------
sungam
How do you account for the observation that incidence of cancer in young,
immunosupressed individuals (e.g. solid organ transplant recipients), whilst
increased, is no way comparable to that seen in elderly individuals?

~~~
reasonattlm
Other age-related cell and tissue damage that raises the risk of cells
becoming cancerous, or reduces the effectiveness of internal-to-the-cell
controls that can shut down and destroy cancerous cells, would be the other
variable, I'd imagine.

~~~
sungam
I think far more likely that the predominant variable is the expansion of
mutant clones over time to occupy large fractions of the stem cell reservoir.

~~~
reasonattlm
Possibly so, which is a phenomenon that might explain how stochastic nuclear
mutation at its given rates can possibly cause widespread enough harm to be
significant. There is an interesting recent paper on that subject:

[https://doi.org/10.1371/journal.pgen.1007108](https://doi.org/10.1371/journal.pgen.1007108)

"Recent single-cell studies point to the possibility that essentially all
cells have unshared mutations in their genomes. In view of this extensive
genetic diversity, it is perhaps not surprising that mutations that confer a
proliferative advantage are readily detected as clonal populations of
increasing abundance and size in the elderly. These clonal populations might
lead to loss of organismal health through the functional decline of tissue
and/or the promotion of disease processes, such as cancer. In this review, we
summarize recent research that supports the notion that aberrant clonal
expansion (ACE) resulting from cancer-associated mutations are common in
noncancerous tissue and accumulate with age. We propose ACE to be a previously
underappreciated aging phenotype that is universal in most organisms, affects
multiple tissues, and likely helps explain why aging is the biggest risk
factor for cancer."

~~~
sungam
I have shown that in elderly individuals essentially the entire epidermis stem
cell compartment, whilst having normal morphology, is occupied by clonally
expanded mutant stem cells:-

[https://www.nature.com/articles/s41467-017-00993-8](https://www.nature.com/articles/s41467-017-00993-8)

~~~
nonbel
That sounds very interesting, but after glancing at your figures, I don't see
where you make this obvious.

Also, in the intro you say "the risk of skin cancer increases exponentially
with age and is associated with accumulation of somatic mutations8". Your
source groups ages into only 3 categories... If you look closer at the data
you will see that developing most cancers becomes less common in old age
(peaks at 60 - 90 years old). For cancers involving tissue like bone or
reproductive organs this peaks much earlier, probably due to when the majority
of cell divisions are occurring.

------
commandlinefan
I worked for a cancer research startup a few years ago - I was just doing IT
stuff, but I worked with a lot of oncologist/cancer research types. One of the
things that they often said was that every living organism will develop cancer
eventually, but most things die of other causes before that happens.

~~~
ngvrnd
it seems plausible or maybe even likely that everyone develops cancer many
times, or at least the beginnings of it, but the immune system kills it over
and over.

Until it doesn't.

------
truculation
If the immune system has finite resources, would reducing the lifetime drain
on those resources by infectious diseases delay the age at which we can expect
get cancer? For example, curing the common cold and/or developing a universal
flu vaccine.

~~~
rsync
"If the immune system has finite resources, would reducing the lifetime drain
on those resources by infectious diseases delay the age at which we can expect
get cancer?"

I would wager the opposite is true. Body systems maintain themselves and their
fitness and function through _use_.

The obvious examples are bone and muscle tissue that become stronger through
stress but are you aware that breast cancer incidence is strongly, negatively
correlated to frequency and duration of breastfeeding ?

The immune system is also a bodily system and I would be surprised if it did
not, also, strengthen itself and maintain its function through stresses and
use.

"For example, curing the common cold and/or developing a universal flu
vaccine."

Be careful what you wish for ...

We "cured" hard physical labor and traditional life patterns with lots of
walking and standing. How's that working out for us ?

~~~
jimmy1
> We "cured" hard physical labor and traditional life patterns with lots of
> walking and standing. How's that working out for us ?

I'll bite -- terribly. Many of the millennial generation and younger are
actively starting to revolt against these sedentary lifestyles. It's why
fitness and fitness culture is so marketable these days, much more than I
remember. I think the studies that came out showing the millennial were the
first generation since the industrial revolution to have a _decreased_ life
expectancy versus the prior generation was a real wakeup call.

~~~
truculation
Yes, not having to do physical labour is better than being _forced_ to do
physical labour as a worker or peasant. The new problem for most people is how
to eat less and get a little exercise. But this is a better problem.

I like rsync's main point though about the immune system maybe requiring usage
and callibration (gojomo mentions the _hygiene hypothesis_ ). Perhaps one day
we'll determine the precise amount of these required (if any) for us to be
healthy without being bothered by too much sickness.

------
agumonkey
Cue the senescence guys who aim to fix accumulated damages there.

~~~
ShabbosGoy
Ultimately, I think it comes down to metabolism. As you age, your metabolism
slows. Coenzymes like NAD+[0] are depleted.

[0]
[https://www.nature.com/articles/nrneph.2017.5](https://www.nature.com/articles/nrneph.2017.5)

~~~
glibgil
Right, so just back up a step and stop the metabolism from slowing

~~~
shrimp_emoji
Or cut the knot. Upload mind to digital facsimile.

Die, per nature's capricious designs.

Robo-you lives _smugly_ without any of this nonsense and can be resurrected if
the power cuts out and sent across the stars at light speed with no need for
fuel or supplies-- _breathes_

... to somewhere without air.

~~~
agumonkey
I don't get why people go after these virtual things

------
Thriptic
Isn't this a bit of an oversimplification? It's not like if you knock out p53
and something else you instantly get a metastatic tumor. Granted if you remove
key tumor suppressor genes your probability of mutations persisting
skyrockets, but that in itself doesn't create a dangerous tumor. You need many
more mutations than 2 to be able to acquire the functionality to grow,
persist, escape the local environment, and establish a foot hold in a new
environment.

Here is the classic review paper on tumor formation:
[http://www.cell.com/abstract/S0092-8674(11)00127-9](http://www.cell.com/abstract/S0092-8674\(11\)00127-9)

------
thrownaway954
I was told once (by who I don't remember):

Live long enough and you will eventually get cancer.

To me it's a no-brainer. You get old, cells break down, immune system isn't
what it use to be, increasing the risk of that rouge new cell becoming
cancerous.

------
moosekaka
Obligatory link to yesterdays topic

[https://gravityandlevity.wordpress.com/2009/07/08/your-
body-...](https://gravityandlevity.wordpress.com/2009/07/08/your-body-wasnt-
built-to-last-a-lesson-from-human-mortality-rates/)

------
samstave
What are white blood cell counts in someone who is sixty vs one who is
eighteen?

Is this where the blood transfusion concept is strong?

What is the oxygen-carrying-capacity of hemoglobin in old blood vs young
blood?

------
reasonattlm
Paper:
[https://doi.org/10.1073/pnas.1714478115](https://doi.org/10.1073/pnas.1714478115)

Which is a suggestive model, by the way, not direct evidence. The best direct
evidence would be to restore the pace of immune cell creation - such as via
regeneration of the thymus (via FOXN1, or BMP4, or tissue engineering), cell
therapy to replace or increase the pool of hematopoietic stem cells, etc. -
and then see what happens. This sort of thing is five years out; there are
people working on it, though more of those and more funding would certainly be
a good thing. It would certainly be possible to push forward a startup today
based on thymic regeneration or hematopoietic stem cell transplantation; the
science is more or less ready for it.

\--------

T cells develop from hematopoietic stem cells as part of the lymphoid lineage
and have the ability to detect foreign antigens and neoantigens arising from
cancer cells. In the thymus, lymphoid progenitors commit to a specific T cell
receptor and undergo selection events that screen against self-reactivity.
Cells that pass these selection gates then leave the thymus, clonally
expanding to form the patrolling naive T cell pool.

The vast majority of vertebrates experience thymic involution (or atrophy) in
which thymic epithelial tissue is replaced with adipose tissue, resulting in
decreasing T cell export from the thymus. In humans, this is thought to begin
as early as 1 year of age. The rate of thymic T cell production is estimated
to decline exponentially over time with a half-life of ∼15.7 years. Declining
production of new naive T cells is thought to be a significant component of
immunosenescence, the age-related decline in immune system function. With the
recent successes of T cell-based immunotherapies, it is timely to assess how
thymic involution may affect cancer and infectious disease incidence.

It is clear from epidemiological data that incidence of infectious disease and
cancer increases dramatically with age, and, specifically, that many cancer
incidence curves follow an apparent power law. The simplest model to account
for this assumes that cancer initiation is the result of a gradual
accumulation of rare "driver" mutations in one single cell. Furthermore, the
fitting of this power law model (PLM) can be used to estimate the number of
such mutations. Exponential curves have also been used to fit cancer incidence
data, resulting in worse fits than the PLM overall. Nevertheless, it is worth
noting that exponential rates close to the declining curve for thymic T cell
production can be seen to emerge from the incidence data, indicating the
relevance of the thymic involution timescale. While the PLM fits well, it does
not account for changes in the immune system with age. To better determine the
processes underlying carcinogenesis, we asked whether an alternative model,
based only on age-related changes in immune system function, might partly or
entirely explain cancer incidence.

Our model outperforms the power law model with the same number of fitting
parameters in describing cancer incidence data across a wide spectrum of
different cancers, and provides excellent fits to infectious disease data. Our
hypothesis and results add to the understanding of infectious disease and
cancer incidence, suggesting in the latter case that immunosenescence, rather
than gradual accumulation of mutations, serves as the predominant reason for
an increase in cancer incidence with age for many cancers. For future
therapies, including preventative therapies, strengthening the functionality
of the aging immune system appears to be more feasible than limiting genetic
mutations, which raises hope for effective new treatments.

\-------

------
HumanDrivenDev
Really? I figured as we age our cancer rates will plummet while our immune
systems only strengthen, which is why the leading cause of the death in the
elderly is extreme sports.

~~~
josephv
I'm with you, upvoted for voicing the absurdity of the title. The article,
which I refuse to read completely, seems like mediocre pop health science and
this website has devolved into giving it, at this point at least 16 hours of
frontpage time.

I'll summarize it: "We don't understand cancer but we'll keep throwing shit at
the wall until something sticks, and we're going to write up a bunch of shit
and you shits read it so we can pay for throwing more shit."

