
Bodybuilding supplement promotes healthy aging and extends life span in mice - pella
https://www.sciencemag.org/news/2020/09/bodybuilding-supplement-promotes-healthy-aging-and-extends-life-span-least-mice
======
rvanlaar
Uh oh, mice in labs are not like humans in this regard at all.

Lab Mice have extraordinary cell repair capabilities. My guess is that the AKG
slows down cell division.

This podcast delves into the problem with lab mice and explains the trade offs
that happen on an evolutionary and cellular level in mice with regards to
longevity.

[https://www.youtube.com/watch?v=JLb5hZLw44s](https://www.youtube.com/watch?v=JLb5hZLw44s)

~~~
nabla9
As a rule, all anti-aging studies and experiments lose effectiveness as the
size and the natural life span of the animal used increases.

It's relatively easy to dramatically increase the natural lifespan of C.
elegans with gene editing, drugs or even caffeine. Mice lifespan is little
harder but doable. Anything that extends healthy human lifespan more than 5%
is not in the radar.

~~~
dcolkitt
My cursory understanding is that actuarial senescence (the increase in
mortality rates for older populations) is not the primary driver of life span
in most mammals.[1] Particularly small mammals, like lab rats. Whereas for
first-world humans, it's the primary driver.

Actuarial senescence makes it devilishly difficult to achieve significant life
expectancy gains. Because mortality rates increase with age, life expectancy
gains only scale O(sqrt(N)) with mortality reductions. Paradoxically a 40%
reduction in all-cause mortality across all ages only adds 5 years of life
expectancy.[2]

The problem with life extension studies is small animals is that we may be
measuring the wrong thing. A true breakthrough in human life spans will
require slowing the rate of actuarial senescence. A wonder drug that only
targets base rate mortality might double the mouse life span, but only add a
few years to human life.

[1]
[https://journals.plos.org/plosbiology/article?id=10.1371/jou...](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000432)
[2]
[https://joshmitteldorf.scienceblog.com/2012/11/10/mortality-...](https://joshmitteldorf.scienceblog.com/2012/11/10/mortality-
and-life-expectancy/)

~~~
mrfusion
But just increasing health span would still be a huge win for humans.

------
sradman
The paper _Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and
Compresses Morbidity in Aging Mice_ [1]:

> We find that CaAKG promotes a longer, healthier life associated with a
> decrease in levels of systemic inflammatory cytokines.

Judging from the image of black mice in the article, the C57BL/6 strain of lab
mice [2] are used in the study. This strain has long telomeres which should be
taken into consideration with all the other caveats associated with longevity
studies in mouse models.

If you are an optimist, then the hypothesis that AKG [3] supplementation
safely reduces age related systemic inflammation is a positive outcome.

[1] [https://www.cell.com/cell-
metabolism/fulltext/S1550-4131(20)...](https://www.cell.com/cell-
metabolism/fulltext/S1550-4131\(20\)30417-4)

[2]
[https://en.wikipedia.org/wiki/C57BL/6](https://en.wikipedia.org/wiki/C57BL/6)

[3] [https://en.wikipedia.org/wiki/Alpha-
Ketoglutaric_acid](https://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid)

------
ovi256
This is great news if you're lab mice!

[https://twitter.com/justsaysinmice?lang=en](https://twitter.com/justsaysinmice?lang=en)

This is a parody twitter account that reminds us that all these new health
breakthroughs are, indeed, applicable to mice only.

It's a horribly narrow funnel that filters these to what is applicable to
humans, outside a lab.

------
cmendel
Alpha-ketoglutarate for those who don't want to read the article.

Here's the Wikipedia page: [https://en.wikipedia.org/wiki/Alpha-
Ketoglutaric_acid](https://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid) I
don't expect it to be terribly helpful though, it's a bit dense to the
layperson.

~~~
SenorTibbs
It's a metabolic intermediate of the citric acid cycle - the cycle is needed
to reduce electron carriers (NAD+/FAD) which are then used to drive the
electron transport chain for making ATP. In simplest terms: it's an important
part of aerobic respiration.

That being said, it can be synthesized de novo very easily so long as your
cells have enough glucose/fatty acids and enzymes are functioning properly.
It's even formed directly by deamination of glutamate. I'm not sure these
results would be very transferrable to humans.

------
davidu
Tim Ferriss had this amazing comment once in one of his books that if you want
to know what the future of human health is in 5 years, look to what
bodybuilders are doing today, and if you want to look at the future of human
health 10-15 years out, look to what race horse breeders are doing. Something
to that effect. ;-)

~~~
0134340
Really? I don't think either are known for their long lives.

~~~
Scoundreller
It’s a grim looking future...

------
throwaway4good
Why do we need to mouse experiments when a large number of bodybuilders have
moved straight to human trails?

~~~
globular-toast
The drugs bodybuilders and other athletes take are often illegal and they are
highly secretive about it. It's a big problem when trying to do any kind of
science on these drugs.

~~~
bluedevil2k
Not sure why you're getting down voted, you're definitely right. Bodybuilders
are often taking steroids, and the more serious ones are taking HGH and
insulin (not illegal, but not a standard supplement either). From the article
linked below "we estimated that among Americans currently age 13 to 50 years,
2.9–4.0 million have used AAS (anabolic androgenic steriods)." They are
secretive about it with most not wanting to bust that "I'm natural" myth about
them. Instagram guys are notorious for that. Watch a YouTube video by Seth
Feroce, a body builder who is very open about his steroid use, and you'll see
just how many illegal drugs these guys use.

* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961570/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961570/)

~~~
globular-toast
A lot of people don't want it to be true and this is a standard reaction to
that. The truth is performance enhancing drugs (PEDs) in general are a dirty
little secret that are used widely in some of the top echelons of society. Top
sportsmen, movie stars, bodybuilders, models, you name it, they're all on PEDs
to some extent.

------
OneGuy123
Ketones kick in a no-carb diet/fasting: so this can be connected to the
knowledge that calorie restriction extends lifespan: both this supplement and
calorie restrictions have ketone production/supplementation in common, so
perhaps life "extension" has ketons at its root.

~~~
qeternity
The human body can actually consume a fair number of carbs and still be in
ketosis. I think of the big marketing problems that ketogenic diets have is
the perception that it’s “no carb” which makes it almost impossible in modern
life (oh no, I have a work lunch and everything has some small amount of
carbs).

~~~
actuator
Was there any reason that keto diets became popular? In my personal experience
a diet high in proteins with overall calorific deficit works the best. Carbs
seem to keep me more energetic, workouts are better and I have much more
options on what I can eat.

I have seen it being quoted that Keto's effectiveness has been proved but is
it any better than a balanced high protein diet.

~~~
narag
Keto, in any of its multiple incarnations, works. That's why it became
popular. I just lost 20 kg if you like anecdotes. I first heard about it in
the 70's when it became popular in Spain. That time it was called Atkins.

It has always been controversial and there has been a lot of disinformation
about it. If you want to see an example look in Wikipedia the difference in
tone between articles about Atkins or ketogenic diets and ketosis itself.
While ketosis seems like a regular metabolic process as any other, anything
about the diets is pictured as controversial and pseudoscientific, even if
it's just based on ketosis.

I just stopped caring. The diet itself is much easier to follow now than it
seems. There are tons of information in the web, a lot of products and carbs
tables. In particular, what I do now different is using a lot more of vegetal
food: avocados, broccoli, salads and less protein, but still some unprocessed
beef, poultry or fish every day. Erytritol is nicer to my guts than other
sweeteners, too. Oh, and don't forget vitamins supplements, specially B1 to
accelerate metabolism, but the more complete the better.

I exercise regularly with no problems, gaining some muscle at the same time
that I lost fat. And my last blood analysis gave some superb numbers.

Edit: protein shakes that I bought for the gym are also a nice trick.

~~~
meowzero
Keto “works” (which I assume you mean for weight loss) because it helps people
get into a caloric deficit easier. High fat and moderate protein is highly
satiating and helps people to eat fewer calories without needing to track
calories closely. Of course, it’s also possible to gain weight if you eat at
caloric surplus in Keto.

Also, since carbs are virtually eliminated, most of the weight loss in the
beginning is water and glycogen.

Gaining muscle while losing fat is possible in a regular diet. That’s called
newbie gains. And since you lost weight, your blood numbers improved.

Since keto works for you, it’s great. But I wanted to clarify that your result
is not specially because of the keto diet. It can be achieved with just about
any diet.

~~~
narag
So you think that ketosis doesn't exist and that I've lost 20 kg of water and
glycogen?

Or are you trying to make a point out of things you didn't say?

~~~
meowzero
Ketosis exists. You didn’t just lose 20kg of water and glycogen. In the
beginning you probably did though.

My point is that everything you did is possible with a regular diet. You can
lose weight, improve blood numbers, gain muscle/lose fat at same time, etc.
with a regular diet.

~~~
nmfisher
> My point is that everything you did is possible with a regular diet. You can
> lose weight, improve blood numbers, gain muscle/lose fat at same time, etc.
> with a regular diet.

True, but keto (or at least "low carb") makes it much, much easier to manage
your hunger/appetite/satiety signals.

You'd really have to go to a lot of effort to overeat on meat and vegetables.

------
Lio
This is a really interesting article.

Does anyone with a medical background have an opinion on how we should balance
this against studies[1] that indicate reducing the bodies natural production
of alpha ketoglutarate may reduce the likelihood of in operable brain tumours?

It's not like I would rush out and act on either report because as a layman I
can't really assess the findings.

1\. [https://www.nih.gov/news-events/news-releases/drugs-
against-...](https://www.nih.gov/news-events/news-releases/drugs-against-
alpha-ketoglutarate-may-combat-deadly-childhood-brain-tumor)

------
mrfusion
So why is this a body building supplement?

~~~
m0llusk
L-Arginine Alpha Ketoglutarate (AAKG) is advertised as a Nitric Oxide
increasing agent to improve results of exercise on muscles, improve protein
synthesis generally, and growth hormone secretion. All of these assertions are
rather vague and have at best limited scientific support, but it is considered
a diet supplement and is known to be safe even at high doses so there is
little regulation that applies.

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koolhead17
Sample Size? Who financed this?

~~~
swebs
Here's the paper.

[https://www.biorxiv.org/content/10.1101/779157v1.full.pdf](https://www.biorxiv.org/content/10.1101/779157v1.full.pdf)

------
xwdv
There’s only three supplements worth taking:

 _Creatine_ \- to top off your bodies ATP stores and maximize power output.

 _Beta Alanine_ \- to maximize your carnosine stores and decreasing the
burning pain that comes from lactic acid, letting you push harder for longer.

 _Citrulline_ \- to relax blood vessels and boost nitric oxide in your body,
giving your muscles more oxygen for more work and powerful erections.

When their powers combine, you can reach your max potentials, with correct
dosing.

~~~
RankingMember
Re: beta-alanine, anecdotally all it ever seemed to give me were strong
tingling feelings. Maybe I'll give it a go again sometime.

> giving your muscles more oxygen for more work and powerful erections.

hopefully not both at once ;)

~~~
xwdv
You have to take them for quite some time. The tingling should stop happening
after some times.

