
Molecule produced during fasting has anti-aging effect on vascular system - sahin-boydas
https://newatlas.com/molecule-fasting-vascular-system/56360/
======
fabricexpert
Can we update the title to reflect the research by adding "in mice" at the end
of it?

The effect of calorie restriction on aging in rodents has been known since the
1930s. Which does not diminish the value of identifying the precise molecule
that triggers this, but it does mean that this shouldn't necessarily be used
as justification for a fasting diet.

"It has been known since the 1930s that reducing the number of calories fed to
laboratory rodents increases their life spans. The life extension varies for
each species, but on average there was a 30–40% increase in life span in both
mice and rats.[30] In late adulthood, acute CR partially or completely
reverses age-related alterations of liver, brain and heart proteins, and mice
placed on CR at 19 months of age show an increases in life span.[78] "

[https://en.wikipedia.org/wiki/Calorie_restriction](https://en.wikipedia.org/wiki/Calorie_restriction)

~~~
ransom1538
Here is one monkey on an unrestricted diet and one monkey on a restricted diet
years later:

[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)

~~~
lukeschlather
That article in its entirety is interesting, because there are not two but
four monkeys from two different studies. Two on "restricted diets," and two on
"unrestricted diets."

In one study they fed both monkeys a highly processed diet of 30% sucrose. In
the other study they fed both monkeys a less processed diet of 4% sucrose.

The monkey with the poor health outcome was the one allowed to eat as much as
it wanted of the highly processed 30% sucrose diet.

So the "calorie restriction" seems to more likely just mean "don't eat more
than 4% sugar, unless you are on an extremely calorie restricted diet."

~~~
flatb
I'm no expert, and I might be wrong, but generally I would argue against
extracting conclusions (even layman conclusions) from two studies of a
different species (!) with a sample size of 2 (!!!)

------
bodhibyte
I'm on a day 4 of a water-only fast and have completed a two-week medically
supervised fast as well as many other shorter fast.

As an anecdote, I can say water-only fasting in combination with a high
nutrient density plant-based diet has helped me overcome some serious
allergies and other health conditions. As an added bonus, I've lost 65 pounds
from my peak weight over the last few years and my weight has been stable.
It's not a panacea, but I've found it to be a net benefit.

For those interested in a deeper dive on the benefits of water-only fasting
and diets that try to mimic its benefits, as well as time-restricted feeding,
see:

Valter Longo, Ph.D. on Fasting-Mimicking Diet & Fasting for Longevity, Cancer
& Multiple Sclerosis [1]

Dr. Valter Longo on Resetting Autoimmunity and Rejuvenating Systems with
Prolonged Fasting & the FMD [2]

Dr. Satchin Panda on Time-Restricted Feeding and Its Effects on Obesity,
Muscle Mass & Heart Health [3]

Dr. Satchin Panda on Practical Implementation of Time-Restricted Eating &
Shift Work Strategies [4]

[1]
[https://www.youtube.com/watch?v=d6PyyatqJSE](https://www.youtube.com/watch?v=d6PyyatqJSE)

[2]
[https://www.youtube.com/watch?v=evGFWRXEzz8](https://www.youtube.com/watch?v=evGFWRXEzz8)

[3]
[https://www.youtube.com/watch?v=-R-eqJDQ2nU](https://www.youtube.com/watch?v=-R-eqJDQ2nU)

[4]
[https://www.youtube.com/watch?v=iywhaz5z0qs](https://www.youtube.com/watch?v=iywhaz5z0qs)

[Edit to fix typos and formatting]

~~~
riffraff
why are allergies supposed to be affected by fasting?

~~~
dpatrick86
Valter Longo's work has shown that fasting causes a destruction of immune
cells that get renewed from progenitors (absent the autoimmunity) after the
refeeding phase. The mechanism has been shown to help with an animal model of
multiple sclerosis called experimental autoimmune encephalomyelitis.

It's a very elegant, most likely conserved mechanism that may generalize to
virtually all diseases of autoimmunity and not just multiple sclerosis.
However, that obviously needs to be proven clinically before you can say that
and it might take a while.

Also, the conversion of animal research to human has another challenge:
rodents have a faster metabolism. To have any hope of recapitulating those
type of effects, you really have to go a while without food.

There seems to be a more medically safe way of probably tapping into mostly
identical effects though, which is a "fasting-mimicking diet." Ultra low
calorie, fits a specific macronutrient profile.

Read the show notes for this episode or watch the video...
[https://www.foundmyfitness.com/episodes/valter-
longo-2](https://www.foundmyfitness.com/episodes/valter-longo-2)

~~~
bodhibyte
Thanks, couldn't have said it better myself.

I was initially pretty concerned about the safety of water-only fasting. It
appeared so extreme. After spending two weeks fasting with others who are
either ill with different conditions or very healthy, I realized that it's
relatively safe given good medical supervision.

When fasting on my own, I haven't fasted longer than 5 days, and I know what
to watch out for now:

\- I check my blood pressure and heart rate every morning

\- I get up very slowly (as you can get light headed and fall if you're not
careful)

\- I bathe without taking a hot shower or submerge my body in hot water as
this can lead to low blood pressure as well.

------
amacbride
I know it's just one data point, but I've been doing a very mild form of
intermittent fasting (more time-restricted eating) since June, and have been
very happy with the results. (I stop eating by 8pm, don't start again until
noon, but haven't done much in terms of changing what I'm actually eating.) At
5'5", I went from 156lbs. to 143 (goal is 135), and it's been relatively easy.

Your mileage may vary, of course, but I feel great. This was inspired by a
paper I read (I believe linked-to in this article, but I'll have to track it
down later.)

[https://www.the-scientist.com/features/running-on-
empty-3143...](https://www.the-scientist.com/features/running-on-empty-31436)

~~~
phkahler
Close your eating window to 4 hours and eliminate carbs. You'll drop weight
incredibly fast. Delay lunch until 1-2pm and then have an early dinner if you
can't bring yourself to eating just one meal a day.

I did this and it is amazing, but I failed to keep it up long enough to become
my normal.

~~~
naasking
Losing weight fast is not a desirable goal. You can lose considerable muscle
mass, even around your heart which is obviously dangerous.

~~~
justtopost
This is FUD. Please cite your sources.

While not healthy to literally starve yourself, getting your calories from
stored fat is absolutely safe. There are dozens of documented cases of people
subsisting on vitimins/broth and their own fat for over a year. Proper
electrolytes all but eliminate most issues you suggest, only applicable to a
pure starvation diet. Conflating the 2 is either uninformed or dishonest.

~~~
consp
In general, muscle is 'consumed' before 'fat'. Quotes since it is more complex
than just what regular muscle and fatty tissues do.

> _While not healthy to literally starve yourself, getting your calories from
> stored fat is absolutely safe._

No one will disagree with you there, but for most normal healthy people with
regular muscle/fat content (or a bit too much) it takes a while for your body
to decide it is a good idea to start creating toxins (ketones, which are quite
harmless in smaller quantities) which are the result of fat conversion in a
starvation diet.

~~~
joycian
If that is true, then why even have fat instead of extra muscle?

Burning muscle before fat makes no evolutionary sense.

~~~
sergiosgc
> If that is true, then why even have fat instead of extra muscle?

Higher density, lower basal metabolic rate increase.

> Burning muscle before fat makes no evolutionary sense.

The chemical pathway for getting energy from muscle is much shorter than the
one to get energy from fat.

~~~
joycian
So our ancestors would just die of starvation and get weaker and weaker, while
keeping their fat stores?

~~~
Retric
No, but the optimum solution to survive long term starvation is to dump as
much muscle mass as possible to minimize your daily calorie burn. Alongside
that the body minimizes the energy spent fighting long term problems like
cancer by reducing the amount of antioxidants produced etc.

Some strength is still required, so their are feedback mechanisms limiting
this loss. However, on a diet you are not in pure survival mode so you
probably don't want to make those same sacrifices.

~~~
nradov
That's a myth. Extra muscle doesn't contribute very much to resting metabolic
rate. Fat isn't metabolically "free" either; it takes a lot of energy just to
move adipose tissue around.

[https://muscleevo.net/muscle-metabolism/](https://muscleevo.net/muscle-
metabolism/)

~~~
Retric
In starvation it's calories not pounds that's critical, also it's not a
question of resting metabolic rate alone.

Fat contains contains more than twice the energy per lb and every motion you
do requires energy to move every lb of body weight. Net result storing energy
in Fat takes ~1/3 the energy to maintain.

So, sure it's not a huge difference per day. But, the difference between dying
in 100 days or 100 + X days could make a huge difference.

~~~
arcticbull
You're gonna need to cite some sources. Our side has studies to show you're
wrong, and so far you've got nothing but your anecdotes.

~~~
Retric
“Within FFM, skeletal muscle (-5%)”

"Thirty-two nonobese men underwent sequential overfeeding (1 wk at +50% of
energy needs), CR (3 wk at -50% of energy needs), and refeeding (2 wk at +50%
of energy needs). AT and its determinants were measured together with body
composition as assessed with the use of quantitative magnetic resonance,
whole-body MRI, isotope dilution, and nitrogen and fluid balances."
[https://www.ncbi.nlm.nih.gov/m/pubmed/26399868/](https://www.ncbi.nlm.nih.gov/m/pubmed/26399868/)

So, over 6 weeks they had zero calorie deficit but even 3 weeks of starvation
result cost them 5% of their skeletal muscles lower metabolic rate, and
presumably increased fat. Note: Interment fasting has nothing to do with this,
it takes the body several days respond to starvation a few hours don't matter
as long as net calories over 2-3 days are maintained.

PS: What studies? I see a linked to an article about people over estimates of
mussels energy requirements not a counter argument. You’re demonstrably wrong
from both experiment and basic biochemistry.

~~~
arcticbull
That's actually different, you're talking about calorie restriction (-50% of
needs), what we've been discussing is fasting (0% of needs). There are
substantial physiological differences between the two modes, and that study is
not relevant to this conversation. Fasting actually improves your body
composition (reduces proportion of fat : muscle) [5]. Further, even if you
regain all the weight you lost, you'll still have a better body composition
after fasting vs. CR [6].

Speculatively, even the reduced amount of food will suppress HGH production -
while total abstention yields many hundreds of percent increase in levels [3,
4]. HGH is known to be responsible conserving muscle and improving body
composition.

It's been shown in studies that fasting raises your metabolic rate [1, 2]
(again, offer not applicable to CR, by your own study and some others I don't
have on hand right now). This is likely due at least in part to the production
of norepinephrine during fasting. This further substantiates my point that
we're talking about two different modes of operation.

CR != Fasting.

FWIW I agree with you, reducing your calorie consumption 50% but maintaining
your 3-a-day plus snacks eating schedule is not great for you ("starvation")
and likely damn hard to stick to. Weight Watchers themselves published a study
that showed it just doesn't work. [7] This is what they were testing during
the Minnesota starvation experiment and that didn't go well, to say the least.
What my review of numerous studies indicates, is that the relationship does
not extend to reducing your caloric intake 100% (obviously, intermittently for
some value of intermittent). What it appears is being re-discovered is that
it's not how much you eat, but what you eat, and how when/how often.

[1]
[https://www.ncbi.nlm.nih.gov/pubmed/14066725](https://www.ncbi.nlm.nih.gov/pubmed/14066725)

[2]
[https://www.ncbi.nlm.nih.gov/pubmed/10837292](https://www.ncbi.nlm.nih.gov/pubmed/10837292)

[3]
[https://www.ncbi.nlm.nih.gov/pubmed/3127426](https://www.ncbi.nlm.nih.gov/pubmed/3127426)

[4]
[https://www.ncbi.nlm.nih.gov/pubmed/1548337](https://www.ncbi.nlm.nih.gov/pubmed/1548337)

[5]
[https://www.ncbi.nlm.nih.gov/pubmed/17413096](https://www.ncbi.nlm.nih.gov/pubmed/17413096)

[6]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042570/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042570/)

[7] [https://fatfu.wordpress.com/2008/01/24/weight-
watchers/](https://fatfu.wordpress.com/2008/01/24/weight-watchers/)

~~~
Retric
I specifically commented on someone saying “our ancestors would just die of
starvation”. So, if you want to talk about short term fasting then that’s cool
but really not related to this thread of conversation.

Anyway, I agree under 2 weeks of fasting _is not starvation._ The body does
not go into starvation mode over a few days becase it’s extremely expensive to
cycle building up and removing skeletal muscle.

PS: It generally takes 24 to 72 hours for food to move through your digestive
tract. In the very short term fasting you get excess energy because digestion
takes energy. But extend that for 3+ weeks and very different things start
happening.

~~~
arcticbull
My reading implies that the number of muscle cells does not change and that
protein in the muscles is rapidly rebuilt upon re-feeding.

Entering 'starvation mode' from studies appears to happen around day 3-5 of
fasting, there's charts in the links I provided. That's when the new energy
distribution is in full effect and the brain is deriving most of its required
energy from ketone bodies. If you have some interesting stuff to read about
another shift that happens around 2 weeks I'd love to check it out, I'm always
looking to learn more about this stuff. When 'starvation mode' switches to
dying mode appears to be when all your fat stores are exhausted and the body
no longer has fat to consume for energy. If you're obese that can be 12 months
away or more. Most people who fast for long periods note the switchover
happens when their breath turns sweet and a real feeling of hunger returns --
that's obviously when they break the fast so as not to die.

------
phkahler
I hate this:

"we are working on finding a new chemical that can mimic the effect of this
ketone body's function"

They know what the molecule is and it works in mice. I presume they want to
find a _patentable_ molecule to mimic the natural one.

~~~
arcticbull
And they know it can be made in the body, free of charge, by changing eating
schedule. Sounds like maybe convincing people to change their eating schedule
is the way to go?

~~~
titzer
But, but, we can sell them lots of food _and_ diet pills!

------
Apocryphon
Can anyone read the study and actually tell how long or what kind of fasting
did it take to gain those results? The article just quotes a scientist about
fasting for 24 hours.

~~~
sgrytoyr
Since the benefits seem to be linked to ketosis, I believe we’re talking about
fasts longer than 1-3 days, since that’s typically how long it takes to reach
ketosis. So anywhere from 1-14 days, I would think.

~~~
fabricexpert
You can reach ketosis without fasting, it's worrying that both this article
and it's source are not really clear on the methodology.

This the actual source:

"Here we report that β-HB promotes vascular cell quiescence, which
significantly inhibits both stress-induced premature senescence and
replicative senescence through p53-independent mechanisms.

Further, we identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as
a direct binding target of β-HB. β-HB binding to hnRNP A1 markedly enhances
hnRNP A1 binding with Octamer-binding transcriptional factor (Oct) 4 mRNA,
which stabilizes Oct4 mRNA and Oct4 expression. Oct4 increases Lamin B1, a key
factor against DNA damage-induced senescence.

Finally, fasting and intraperitoneal injection of β-HB upregulate Oct4 and
Lamin B1 in both vascular smooth muscle and endothelial cells in mice in vivo.
We conclude that β-HB exerts anti-aging effects in vascular cells by
upregulating an hnRNP A1-induced Oct4-mediated Lamin B1 pathway."

[https://www.cell.com/molecular-
cell/fulltext/S1097-2765(18)3...](https://www.cell.com/molecular-
cell/fulltext/S1097-2765\(18\)30605-1)

~~~
Amygaz
I read it too, and there is absolutely nothing new. Pick any protein network
database, and all these actors are already linked. Basically, you could have
written the same conclusion without sacrificing any mice.

------
andy_ppp
Peter Attia is an interesting person to listen to discussing ketosis and
fasting; in [1] he only eats fat for a week followed by a 1 week fast and a
further week of ketosis afterwards.

In [2] he specifically talks about the benefits of Ketosis in depth with one
of the leading experts in this field.

[1] [https://peterattiamd.com/ama02/](https://peterattiamd.com/ama02/)

[2]
[https://peterattiamd.com/domdagostino/](https://peterattiamd.com/domdagostino/)

~~~
pbhjpbhj
He doesn't eat anything for 1 week in 4?

~~~
andy_ppp
For 1 week at the start and at the end he eats no sugar or carbohydrate.

For 1 week he the middle he drinks water and takes magnesium.

That's it.

------
abcd_f
Relink to [1] perhaps, which is the original source without any anti-
adblocking nonsense?

[1] [https://news.gsu.edu/2018/09/10/researchers-identify-
molecul...](https://news.gsu.edu/2018/09/10/researchers-identify-molecule-
with-anti-aging-effects-on-vascular-system-study-finds/)

------
zerop
I do fast once in a week and I have seen good benefits. I have been doing this
since 2014. This is what I do: Dont eat breakfast, lunch or anything till
dinner. (Some people skip breakfast and dinner). Though I do drink lemon juice
once in the day.

I obviously lost some weight, but more importantly it developed habit to
ignore temptations. I find my self more relaxed overall.

------
lawlessone
All these different supposed anti-aging molecules that our body already
produces.. e.g. nad+ also

I would love if these could be used to slow or even halt aging but i would
worry there is reason the body doesn't produce more of these. It's been said
before but would we be leaving ourselves open to more cancer?

~~~
phkahler
>> i would worry there is reason the body doesn't produce more of these.

It's starting to look like the reason is the modern diet. And by modern I mean
what we shifted to with the advent of farming several thousand years ago. 3
meals a day with high carbohydrate content. This puts you into the mode of
converting carbs to fat for storage and never gives the opportunity to go into
a mode of retrieving fat for energy. One specific reaction to eating carbs is
an insulin response, which can last several hours. It's looking like people
weren't design (evolved) to live that way. Type II diabetes (insulin
resistance) is looking entirely preventable and perhaps reversible if one goes
keto. You're just not going to produce the chemicals needed for one mode of
operation when you're telling the body to do something else. These diets are
proving that you can get it to produce another set of chemical in clinically
meaningful quantities.

~~~
magduf
[https://theoutline.com/post/6133/the-keto-diet-is-a-
recipe-f...](https://theoutline.com/post/6133/the-keto-diet-is-a-recipe-for-
disaster)

------
krtkush
I have observed a surge in articles related to fasting (all of them are
positive about it). Has there been new breakthrough in the field?

~~~
fabricexpert
It won't last - how do you make money off a fasting diet? There's nothing to
sell, unlike WeightWatchers, Shakes, Juice diets etc.

Unless someone sells fasting chewing gum or something.

~~~
mkagenius
For ketosis, you are allowed to eat carbohydrate less food. So, cheese is
fine.

~~~
Amygaz
But then your LDL will rise up, thereby negating any cardiac benefits...

~~~
justtopost
Diatary and Blood collesterol are not casually linked as many erroniously
assume. Easy mistake.

~~~
khelenek
I don't want to get into a heated nutrition debate because it's such a mess
divisive landscape, but wanted to share the other side, which looks
compelling: [https://nutritionfacts.org/2016/03/22/the-effects-of-
dietary...](https://nutritionfacts.org/2016/03/22/the-effects-of-dietary-
cholesterol-on-blood-cholesterol/) And another interesting piece of science
pointing at causation rather than correlation regarding LDL and CAD:
[https://nutritionfacts.org/video/how-do-we-know-that-
cholest...](https://nutritionfacts.org/video/how-do-we-know-that-cholesterol-
causes-heart-disease/)

------
restallus
Coincidentally, Yom Kippur [1] begins tomorrow, when observant Jews fast for
approximately 25 hours.

[1]
[https://en.wikipedia.org/wiki/Yom_Kippur](https://en.wikipedia.org/wiki/Yom_Kippur)

~~~
abraham_lincoln
No food, no liquids, no water.

Is fasting with water less effective?

~~~
restallus
Less effective in what sense? If one included drinking water,
bathing/cleaning, or sexual relations it wouldn't be a proper religious fast,
unless one is excepted from it, e.g. due to health issues. There are no
degrees of effectiveness so to say.

~~~
abraham_lincoln
I meant religous fast versus an occidental fast...

------
mark_l_watson
I am in a study by Stanford University to only eat during a ten hour period
each day. So far, I am sleeping better but subjectively that is all I can say.

I do personally believe that in the past occasional 20 to 24 hour fasting and
not eating after 6pm has increased my feeling of being healthy. My personal
experiences don’t have much meaning so I am looking forward to more proper
scientific studies in the future.

~~~
always_good
I would've thought most people eat within a ten hour window (8-6p, 10-8p,
etc), though probably only if you ignore snacking.

------
YeGoblynQueenne
Looking up details of the study design, the molecule in question,
β-Hydroxybutyrate, was tested in vitro on human tissue, and in vivo only on
mice, so, as usual, wait patiently to see if there is any confirmation in,
say, a large-scale study of a human population.

 _The researchers tested the efficacy of β-hydroxybutyrate against cellular
senescence in vitro on human umbilical vein endothelial cells and human aortic
smooth muscle cells, and they observed the beneficial effects of this molecule
in vivo: by injecting β-hydroxybutyrate into fasting mice, the scientists were
able to alleviate the senescence of the animals’ aortae._

[https://www.leafscience.org/molecule-appears-to-have-anti-
ag...](https://www.leafscience.org/molecule-appears-to-have-anti-aging-
effects-on-the-vascular-system/)

------
ainiriand
How does it fit with intense anaerobic exercise? Is it safe to do? Can I
expect dizziness?

~~~
silverdrake11
I have definitely experienced dizziness and feeling faint while fasting.. I'm
not sure it's safe to exercise.

