
New explanation for middle-age weight gain - sciadvance
https://directorsblog.nih.gov/2017/05/09/muscle-enzyme-explains-weight-gain-in-middle-age/
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Mr24601
PSA: Every legitimate long term study of non surgical weight loss shows that
it doesn't happen for the vast, vast majority of people.

1) ["In controlled settings, participants who remain in weight loss programs
usually lose approximately 10% of their weight. However, one third to two
thirds of the weight is regained within 1 year, and almost all is regained
within 5 years.
"]([http://www.ncbi.nlm.nih.gov/pubmed/1580453](http://www.ncbi.nlm.nih.gov/pubmed/1580453))

2) Giant meta study of long term weight loss: ["Five years after completing
structured weight-loss programs, the average individual maintained a weight
loss of >3% of initial body
weight."]([http://ajcn.nutrition.org/content/74/5/579.full](http://ajcn.nutrition.org/content/74/5/579.full))

3) Less Scientific: [Weight Watcher's Failure - "about two out of a thousand
Weight Watchers participants who reached goal weight stayed there for more
than five years."]([https://fatfu.wordpress.com/2008/01/24/weight-
watchers/](https://fatfu.wordpress.com/2008/01/24/weight-watchers/))

4) [The reason why it's impossible seems to be that although calories in <
calories out works, the body of a fat person makes it extremely difficult
psychologically to eat
less.]([http://www.nytimes.com/2012/01/01/magazine/tara-parker-
pope-...](http://www.nytimes.com/2012/01/01/magazine/tara-parker-pope-fat-
trap.html?_r=2&pagewanted=all)) This is borne out by the above data.

5) [The only thing that does seem to work in the long term is gastric
surgery.]([http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421028/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421028/))

Moreover, you won't find any reputable study on the web where the average
person lost 10%+ of their body weight and kept it off for five years. Not even
one.

The study people sometimes bring up is the national weight control registry.
But it is a heavily self selected group of people who have already lost
significant weight before joining - therefore weeding out most of the failure
rate. And even then, only 20% of their audience lost over 10% of their initial
body weight and kept it off for one year.

~~~
bitexploder
So, how do those of us that manage it do it. Is it really is exceedingly rare,
is it even useful studying us? According to weight watchers me and one other
person out of the thousand did it. Everyone else failed. (I cut 40% weight, 12
years later, kept 25% (or more!) body fat from original cut).

At a high level I radicalized my life style. I have ups and downs, but I be
and a runner and a lifter and I have run hundreds of miles e every year since.
It was complete and sort of stark, but I endured.

My theory as to why people fail -- There is no such thing as will power.
Everyone thinks there is and that they aren't strong enough and that is why
they failed. I think in the very short term there is will power. Hours for
most. Once your higher level thinking is overrun you lose.

My hand wavy theory based on my experience and knowledge; you have to believe
in something with enough intensity that your brain you can't talk to gets on
board and accepts its reality. You have to fight it and use tricks to move
around out of sight to where the higher level you gets what it wants. This is
not a linear path.

~~~
notacoward
> There is no such thing as will power.

There is, but most people don't understand how it works. According to recent
neurological studies, it's a lot like a muscle. In the long term, you exercise
it and it gets stronger. In the short term - and this is the important part -
it can become depleted. If your work requires a lot of will power (including
focus, discipline, initiative) then you'll have little left for other parts of
your life.

This is really what I think a lot of people mean when they say they come home
tired. They're not physically tired, they're not low on energy, but they are
low on _will_. Therefore they tend to settle for the easy or familiar, such as
watching Netflix instead of exercising or eating junk instead of cooking real
food. I can often feel the pull myself, but the fact that I understand and
recognize what's happening helps me resist/manage it.

~~~
winkle
And as with any mental model there are potential pitfalls such as when you
tell yourself your willpower has been depleted. You then have an excuse to
slack off [http://www.nirandfar.com/2016/11/the-way-you-think-about-
wil...](http://www.nirandfar.com/2016/11/the-way-you-think-about-willpower-is-
hurting-you.html). I agree it's hard to make the right choice when your tired,
but the way you think about it will also affect your behavior.

~~~
bitexploder
It is easiest for me to just pretend it does not exist. I guess it is sort of
philosophical (again). When there is no will, decisions are made using a
different system of values and alignment with goals. I don't need "will power"
when my environment pushes me in the right direction and the choices, the ones
I want are naturally aligned with multiple other aspects of my life and less
healthy or negative choices are far out of alignment with that. It requires
constantly remembering, setting, and working towards those goals (fitness,
life, and other).

We obviously aren't just subject to the whims of our environment, we make
choices and can decide things, but after a lot of reading on AI /
neuroscience, and just being alive longer I am becoming convinced the
environment and your perception of it is the single biggest factor. It goes
beyond happiness toward fundamental outlook and beliefs.

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com2kid
Well this could end up being a sort of devil's bargain.

Lower weight, better athletic performance, but increased DNA damage leading to
other problems (I'd guess cancer being high up on that list).

~~~
beefman
"...treatment with DNA-PK inhibitor protects against aging-associated decline
in metabolism and physical fitness without increasing DSBs [double-strand
breaks]... The most likely explanation for this paradox is that the ... DNA-PK
inhibitor, like most inhibitor drugs, is a partial inhibitor at physiological
doses. The residual DNA-PK activity may be sufficient to protect against the
level of DNA DSBs generated naturally."

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devereaux
I wonder how this "middle age weight" gain interacts with practices such as
intermittent fasting, keto diet, 1-meal a day. These practices impact
metabolism.

I also wonder if FDA recommendations of calories per days should be split not
just by sex, but also by age.

~~~
adrianN
The FDA recommendations are mostly bogus since activity level and base
metabolic rate differ enough between otherwise normal people to make some
people fat on the recommended amount of calories and others too skinny.

~~~
NikolaeVarius
Ignoring the fact that the FDA already says its recommendations are for an
average person, it doesn't matter because people don't track calories anyway.
Generally people eat WAY too much for their sedentary lifestyles.

~~~
adrianN
I have a hunch that "the average person" doesn't exist when it comes to
nutrition.

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zupreme
I predict plenty of knee-jerk "We've found the fountain of youth" reactions to
this. I instead think doctors should tread carefully here. This enzyme is
present for a reason. While eliminating it may "cure" certain ills it may
cause others (like cancer).

~~~
icelancer
>This enzyme is present for a reason.

It _might_ be. There is no way to know whether it is there for a (good) reason
or not. Evolution doesn't work that way.

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beefman
This is potentially about more than weight gain. The DNA-PK-mediated pathway
they've discovered looks an awful lot like something you'd design to control
senescence.

The DNA-PK inhibitor used, NU7441, is orally active and the press release even
calls it drug-like. The human-equivalent dose based on bodyweight is about
3g/day (three pills worth). The actual HED is probably smaller. Currently very
expensive.[1]

1
[http://www.selleckchem.com/products/nu7441.html](http://www.selleckchem.com/products/nu7441.html)

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abraves10001
"While we await the results, the best course to help fight that middle-age
spread hasn’t changed. Eat right and follow an exercise plan that you know you
can stick to—it will make you feel better. Take it from me, a guy who decided
eight years ago that it was time to shape up, stopped eating honey buns, got
into a regular exercise program with a trainer to keep me accountable, and
lost those 30 pounds. You can do it, even without a DNA-PK inhibitor!"

I'm glad the article finished with the above paragraph because while the study
is interesting, Americans don't seem to have unique physical traits that cause
them to gain weight, we just don't have healthy habits. I wonder what the
weight gain in the same time period is in different regions of the world

~~~
akgerber
We have pretty successfully engineered almost all physical activity out of the
normal daily life of a middle-aged suburban American, who move from bed to car
seat to desk chair to car seat to couch to bed with as little walking as
possible in between.

Most other societies make walking (including to and from public transit) and
bicycling much bigger parts of their transportation landscape, rather than
designing new communities to make driving as easy as possible and other means
of transportation impossible, either intentionally or implicitly.

~~~
snuxoll
I work from home, so it's doubly bad for me - I don't even have to walk to a
car, just the couple steps from bed to my office.

I went to Boston for Red Hat Summit last week and it amazed me just how
exhausted I was after all the walking to/from the train stations and around
the convention. I used to bike every day to/from work when I was just a couple
years younger and never felt as sore and tired as I did every day during the
event. I really need to start getting out more, even just walking to the
coffee shop 1/4 mile away on occasion and working from there.

~~~
nradov
If it's practical for you, consider getting a dog. Dogs need to be exercised
every day so it forces you to get out and walk or run at least a couple miles
every day. And by "dog" I mean a real dog, not some fragile inbred abomination
that can't handle a run around the block.

~~~
pacaro
And don't have a yard, or if you do, don't allow letting the dog into the yard
be a stand in for taking the dog for a walk. Obviously that defeats the point
for you, but it also doesn't do the dog any favours either.

My large inbred abomination (Bernese Mountain Dog, cute, cuddly, overbred) has
never lived anywhere with a yard, so gets real walks.

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russellbeattie
Apparently vanillins are DNA-PK inhibitors. Maybe an extra shot of vanilla
extract in my morning coffee and I'll start losing weight??

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nunez
getting loose on your diet and eating all sorts of crap without abandon or
exercise to burn it off explains middle-age weight gain

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dandare
While there are many "unfair" variables at play, your weight is one of the few
parameters you can control in your life. You won't get more hair, rich parents
or strong health. You can't get taller, smarter or good at writing comments.
But you can always decide not to be overweight, or even be in good shape. (but
being an asshole fet shamer is also a decision)

~~~
watwut
Why is other peoples weight so important for you? You choose to spend time in
gym focusing about how you look like instead of doing something useful,
learning new things or working or simply spending time with your children.

Serious, despite all stereotypes, male dominated tech site seems to put way
more importance on look and talks way more about dieting then female dominated
sites I frequent. When did the switch happened and dudes started to be like
that?

~~~
bebopfunk
There are very few things in my life that are as productive as the gym. It
helps my memory, my mental well being, my cognition and my health. I'm unsure
of why you don't consider exercise to be useful. Can you explain? Below I have
included a quote and link to a study that looks into exercises effects on
cognition. As for people's zealousness for exercise on this site, I think its
a result of people wanting to help others. For many, getting into exercise was
the single best decision they felt they've made in their life. And since
almost anyone can make that change, and do it for free, they're trying to
spread the news. If I spend the time to recommend something as small and
inconsequential as an application to someone, it seems absurd that I wouldn't
recommend something like exercise. But that's just my two cents

"The evidence accumulated so far indicates that exercise is a strong promoter
of cognitive health in humans. "

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951958/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951958/)

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jlebrech
insulin imbalance will also cause weight gain.

~~~
notfromhere
doesn't override CICO

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zellyn
Wait, so it's not my constant over-indulgence in free office snacks that did
it?

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5trokerac3
> While the enzyme is known for its role in DNA repair, their studies show it
> also slows down metabolism, making it more difficult to burn fat.

Already known factor and a completely misleading sentence. All this means is
that you have to consume less to get the same results. We already knew that
metabolism slows down as you age. It's a factor in BMR (base metabolic rate)
TDEE (total daily energy expenditure) calculation.

Sadly, articles like this mostly give overweight people another excuse, rather
than a greater understanding of their predicament.

~~~
pharrington
You're misreading this. The novel claim isn't that metabolism slows down
during middle age, but that DNA-PK levels increase during middle age and the
enzyme negatively effects metabolism.

~~~
AstralStorm
In other words it is an explanation, but not an excuse.

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draw_down
It isn't really a new explanation, the explanation is still "your metabolism
slows and you can't eat like you're 22 anymore". It's a tough adjustment to
make and I'm not even that old yet. The best thing I've found that actually
works is a mostly plant-based diet.

~~~
coldtea
> _It isn 't really a new explanation, the explanation is still "your
> metabolism slows and you can't eat like you're 22 anymore"_

The new part is identifying the cause and specific enzyme etc.

As you put it its an almost tautological description of the situation, which
is not what the article is about.

