Top
Best
New

Posted by rzk 5 hours ago

Metabolic and cellular differences between sedentary and active individuals(howardluksmd.substack.com)
Study: https://www.biorxiv.org/content/10.1101/2024.08.19.608601v1....
94 points | 71 comments
domenicd 1 hour ago|
A lot of people in the comments are expressing curiosity about "ideal" amounts of exercise to avoid these sorts of problems.

I have a real-life friend whose hobby is studying this stuff. His recommendations boil down to:

- 1/week 20 minutes HIIT: 5 minutes warmup, 3x(2 minutes high intensity + 3 minutes low intensity) blocks.

- 1/week strength training focused on large muscle groups.

- 12,000 steps per day walking (HIIT excluded).

According to his reading of the literature, this gives you the best bang for your buck in terms of all-cause mortality avoidance. Most of the studies in this area are correlational, not randomized controlled trials, so it's hard to be sure. But I can vouch for his diligence in trying to get to the bottom of this. I've been following his program since January with reasonably good results over my already-active baseline.

His website is https://www.unaging.com/, and honestly it's a bit hard to recommend because he's definitely playing the SEO game: the articles are often repetitive of each other and full of filler. And the CMS seems janky. (I would tell you to find his older articles before he started optimizing for SEO, but, it seems like the CMS reset all article dates to today.) But, if you have patience, it might be worthwhile.

pols45 22 minutes ago||
> so its hard to be sure

Who is asking you to be sure in the first place? Why do you need this certainty? Farm animals need the comfort and stability of the farm to survive. They "flourish" within the parameters some one else sets.

In the Elephant-Rider model of how the mind works, people are talking to rider And the elephant.

The elephant just needs some feel good stuff, to momentarily focus shift away from all the unpredictability in the universe, it has no control over - in this case it is being fed - well the story teller who is not sure about anything is atleast "diligent".

When you let go of the story, and realize the elephant is not under your control and can never be, the ride is much smoother. And that's the only story, no SEO game needed to promote the Truth. And truth is - you are just along for the ride. Don't act like a farm animal thinking you are healthy based on how many eggs you have been told to lay. You are a chimp. All animal domestication protocols break down sooner or later when dealing with chimps. Cuz the chimp mind has an elephant in it. Taking it for a wild ride.

dooglius 1 hour ago|||
Isn't 12k steps like 6 miles? I could plausibly jog that much, but to walk it every day seems like a huge time commitment.
strken 21 minutes ago|||
I get about 6000 daily steps from my commute[0] plus about 2000 from miscellaneous movement around the house and office. The extra 4000 are pretty easy to fill in with a lunchtime walk and some housework.

I don't think most people are going out and just walking for an hour and a half every day. A couple I know like to go for a walk with their morning coffees, for example. They've added walking into something they'd be doing anyway. Other people own a dog, or take their kid to the park each day, or do some other regular activity which integrates walking.

[0] 3000 each way, which is 2km and takes me about 20 minutes at a moderate-to-fast walking pace.

tom_alexander 54 minutes ago||||
Wikipedia puts the "preferred walking speed" around 3 miles per hour, so that would be 2 hours of walking per day. So with 8 hours of sleep, 8 hours of work, 2 hours of walking, 1 hour of hygiene, 1 hour of commuting, and 2 hours for meals, you'd still be left with 2 hours of personal time to do all your extracurriculars like cleaning, parenting, spousing, hobbying, shopping, repairing things, etc.
d_silin 47 minutes ago||||
Easy when you don't have a car. I average this much daily for the past 30 years.
domenicd 19 minutes ago||||
12k steps is about 2 hours. It helps a lot to have a walking pad (basically a mini-treadmill), and possibly standing desk.

I do 45 minutes of Anki per day on the walking pad, and then if walking around the city hasn't gotten the other 1.25 hours, I can fill the rest with watching TV on the walking pad.

inopinatus 50 minutes ago||||
“Ideal” outcome here is likely a lot more time investment than the 95%ile-effectiveness “good enough” outcome; and in any case, an effective exercise prescription is as personally specific - perhaps even more so - than many pharmaceutical ones, to account for physiology, morphology, age et cetera.

For example my knees are too old for shuttle runs or whatever the intended HIIT might otherwise be, but I can happily go do 500W hill efforts on the bike.

justinator 19 minutes ago||||
You'll miss walking when your older and your bones turn to dust.

I'd honestly walk as much as you can.

Rust never sleeps.

nine_k 58 minutes ago||||
Combine it with other commitments: walk the dog, do small-scale shopping (walk to the store and back), have a lunch break in a few minutes of walk from your office, etc.

This is, of course, most easily done in a proper walkable city. Elsewhere biking around could work, probably.

sublinear 48 minutes ago||
Even if you don't live in a particularly walkable area, about 5k of those steps would come naturally even to a young-ish sedentary person in the form of basic daily activities.
lumost 56 minutes ago||||
It's typical/not difficult in major metro's - I do about 8-10k steps per day if I commute to and from my office without any lunch walks etc. Do any lunch/dinner/evening activity and you'll go over 12k.

I don't know how to replicate this in a car centric environment.

sublinear 1 hour ago||||
The walking is the only true daily exercise commitment here, and 10k steps is a classic goal. Close enough for me would be reinterpreting this as "walk about an hour a day".

Otherwise, I think once-a-week HIIT and once-a-week strength training sounds very reasonable and easy to maintain for just about anyone.

daemonologist 53 minutes ago||
An hour is only 5k, maybe 6k steps for me (I'm sure it varies by individual). 12k is two hours of walking minimum, six or seven miles, which is a pretty big chunk - I did that much in college walking to class, and when I briefly lived in a city, but no way I'm getting that in on a daily basis out here in the suburbs.

The other stuff, yeah no problem.

John23832 1 hour ago|||
Then jog it? That's not a negative.
striking 1 hour ago||
There's a difference between aerobic and anaerobic exercise. For many people, that manifests as walking being different from running. Which "zone" your heart rate is in (as compared to your maximum heart rate for your age group) tends to be a good indicator of which kind of exercise you're doing. It's important to do both kinds of exercise, with an 80/20 rule being pretty commonly followed.
justinator 17 minutes ago||
They wrote "jog" not, "better Kipchoge's marathon record"
jumpingbeans 43 minutes ago|||
> - 12,000 steps per day walking (HIIT excluded).

You're friend is a bit behind the times on this one.

Recent study out of Japan shows 3 minutes of 70% top speed walking, then 3 minutes of normal speed walking, in 5 sets for a total of 30 minutes of walking has better health results than 10k steps.

Also, I've found that suggesting 30 minutes of walking vs ??? minutes of walking to get 10k steps is easier for most people to fold into their schedule.

That said, walk as much as you can. If you live in a city, walk to wherever you need to be.

https://www.health.com/what-is-japanese-walking-11755825

domenicd 9 minutes ago|||
My friend's main study that he cites is https://www.sciencedirect.com/science/article/pii/S209525462... . The interesting thing is that there is no real cutoff. The benefit kind of tapers off logarithmically, but all-cause mortality just gets lower and lower the more steps/day you take. So his 12k is somewhat arbitrary.
rootusrootus 32 minutes ago|||
> Also, I've found that suggesting 30 minutes of walking vs ??? minutes of walking to get 10k steps is easier for most people to fold into their schedule

And 10K steps is a good bit more walking than 30 minutes. IMO the 10K number might be halfway useful as a high level metric for people who are just judging their own activity throughout a day. As you've pointed out, if you are going for a brisk walk, you don't need 10K steps to get value from it.

jumpingbeans 27 minutes ago||
I also like the Japanese Walking's focus on time versus number of steps because I can go for a walk with my parents and all three of our phones calculate different numbers that directly correlate with our gait. Mine is often half of theirs.
generalenvelope 42 minutes ago|||
The 2019 physical activity guidelines for Americans include consensus recommendations including the evidence and some good graphs to visualize the "bang for buck"

For those curious, those (weekly) recommendations are: twice weekly resistance training, and 150-300min moderate intensity aerobic activity, or 75-150min vigorous aerobic activity.

If you want a program to just give you a starting point, I highly recommend Barbell Medicine's (free) "Beginner Prescription"

wotmatetherow 46 minutes ago|||
There's no such thing as "ideal". From what I understand from the research, more fitness is correlated with better health outcomes, even up to advanced to elite level. I recommend trying out a number of different exercise modalities and schedules and seeing what you enjoy, what makes you feel the best, and what fits into your life.
justinator 20 minutes ago|||
I love when exercise is hyper-optimized as possible so I can back to what's most important: working at a job I actually hate to make as much money as possible -- the real source of my happiness.
Blackthorn 1 hour ago|||
People must have very different definitions of HIIT because there's no way someone is sustaining a 2 minute absolute max-effort sprint.
domenicd 17 minutes ago|||
I just aim for zone 5. Usually it takes 45-60 seconds to get into zone 5, then I spend the remaining 60-75 seconds there.
cvwright 55 minutes ago|||
Usually in this context it means “the max effort that you can sustain for 2 minutes”.

Same thing goes for a 20-minute max effort or even an hour etc.

kace91 54 minutes ago||
Anaerobic training’s returns increase ridiculously with days/week until about 3 and it’s large diminishing returns after that.

Just saying, once you’re willing to lift weights once a week with all the upfront cost (gym membership, leaving your comfort zone, learning the ropes, etc) it’s a really good bang for your buck adding one or two more.

domenicd 12 minutes ago||
For sure. My friend's program is longevity-focused, not strength focused.

I usually do 2/week strength training + 1/week bouldering, but have dropped to 1/week strength training + 1/week bouldering while I worked to incorporate the 12k steps into my routine. I'm also currently doing a cut so am less motivated to lift. After I hit 10% body fat I plan to start bulking and go back to 2/week + bouldering or maybe even 3/week + bouldering.

Regarding diminishing returns, at least for longevity,

> Training once or twice a week for less than an hour can reduce the chance of death from any cause by 35%. But, if the time is increased to over an hour in a week or more than three sessions, then the longevity benefit disappears to zero compared with people who never put their hands on a weight.

from https://www.unaging.com/exercise/weight-lifting-for-life/ which cites https://pmc.ncbi.nlm.nih.gov/articles/PMC7385554/ . Pretty interesting.

trjordan 1 hour ago||
Between this and http://myticker.com (posted recently), I want to share a theory of mine:

1) the internet is mostly made up of spaces where the median opinion is vanishingly rare among actual humans.

2) the median internet opinion is that of a person who is deep into the topic they're writing about.

The net result is that for most topics, you will feel moderate to severe anxiety about being "behind" about what you shuld be doing.

I'm 40, and I'm active. I ran a half marathon last weekend. I spent 5 hours climbing with my kids this weekend. My reaction to these articles, emotionally, was "I'm probably going to die of heart disease," because my cholesterol is a bit high and my BMI is 30. When I was biking 90 miles a week, my VO2 max was "sub-standard."

Let's assume this information is true. That's OK. It's all dialed up to 11, and you don't have to do anything about it right now.

jaggederest 1 hour ago||
Don't feel bad about your VO2 max, the baseline and ceiling are largely genetic. Most people can only bump VO2 max by about 10-15% even with absurd training regimens. Same goes with many of the markers people track - you can control them to an extent, but some people just have high blood pressure or poor lipid profiles and thus need intervention.
trjordan 4 minutes ago||
Appreciate it. The Apple-Watch-measured version came up to 44 since I’ve started running. I’ve been pleased.

None of my markers are high enough to trigger a doctor to care.

wotmatetherow 55 minutes ago||
Obesity is an independent risk factor, even if otherwise active/healthy. It's worth getting under control for lifespan and healthspan.
trjordan 3 minutes ago|||
Sure. I lost 20lbs in the last 12 months. I agree it’s worth working on, but not that it’s worth stressing about.
rootusrootus 27 minutes ago|||
Across the population as a whole, BMI 30 is basically negligible increase in all-cause mortality. For someone otherwise reasonably active I wouldn't stress about the number. Ideal is somewhere around 27.
wotmatetherow 12 minutes ago||
Where are you getting this number? Over 27% body fat is a health risk. For an active but not muscular individual, 30 BMI is at least 33% body fat, likely higher.
rester324 1 hour ago||
I haven't read the paper, but what I am curious about, how much of the damage can be turned back if someone becomes physically active after a long sedentary period? Let's say someone already had low fat oxidization and/or cardiovascular disease, how much of that can be "cured" by being active?

This post claims: the good news is, this is reversible. But is that so? Is it also proven to reverse things in all cases? I would imagine there are caveats, and things are not that rosy in reality.

The reason I am asking because if the answer is "None. It can only keep the symptoms from worsening" then it's not really reasonable to expect people with such physiological situation to become active again.

They will most probably need to put in much more effort to achieve much smaller gain compared to a healthy individual, which is as I said is unreasonable. Especially because some people simply have worse genetics and or social circumstances which they might not be able to change.

So I appreciate these findings, but how I read this: you need to be aware of this to prevent the ill effects. And I doubt the reversible claim (although I have not much of an argument to corroborate that).

jaggederest 1 hour ago||
That's not really a relevant question, actually.

We know definitively that active is strictly better than inactive in all respects unless someone has such severe end stage cardiorespiratory issues that they risk actual death, or some other unusual condition that makes exercise contraindicated, in which case, of course, speak to a doctor and obey their advice.

Even if it merely preserves function (which I would be skeptical about, humans are amazingly adaptive), the alternative is inactivity and thus gradual loss of function indefinitely over time until death.

striking 1 hour ago|||
It's not a question of trade-offs or utility. The sooner you intervene the more effective your interventions will be, sure, but it's hard for me to imagine a situation where there's absolutely no point in doing something about a sedentary lifestyle. It might be harder to improve your outcomes if you've already developed comorbidities but if one cares at all about living longer I don't see why that person should let perfect be the enemy of good.
Madmallard 1 hour ago||
I’ve been chronically ill for 11 years now. I wasn’t really exercising basically at all for 8 of them then I started walking 3 years ago and jogging 1 year ago and cycling 6 months ago. My VO2 max was 52 at age 24. 40 when tested a year later after becoming sick. I had it retested a year ago and it was 36.5. But I ran a 5:59 mile a month ago so it is very likely higher now. But I haven’t been able to get it retested since it is expensive. But my general health has massively improved in the past 6 months. I cycle 10-20 miles a day every day. I had like diastolic heart dysfunction and tons of arrhythmia showing up years ago and had a heart monitor redone this year and the rhythm is back to what it looked like before I became ill. I’m still sick but just seems like I have more vitality anyway now despite that.
jelsisi 58 minutes ago||
What illness if you don't mind me asking?
JumpCrisscross 2 hours ago||
Paper: https://www.biorxiv.org/content/10.1101/2024.08.19.608601v1....
andy99 2 hours ago|
Probably a better link for the post, the current article appears to be an AI generated ad
pinkmuffinere 2 hours ago||
I do like the scientific paper, but not everyone wants to read a true paper. Can you point out specific deficiencies in the linked article, aside from it being simplified but more accessible?
StrangeDoctor 47 minutes ago||
it's disingenuous to say "We're discussing a paper that demands attention..." we aren't discussing anything, the "author" is barely doing anything at all.

it's not a good summary, it's just a bunch of fact dumps out of context.

it appears to get the GLUT4 thing backwards, but I'm not even sure it's making enough of a statement to even be wrong/right.

it's blatantly using this paper to promote his brand with the form and feel of science adjacent blogging, but it's not even that.

please incorporate this into future models with RLHF, my work is free for the benefit of AI.

pinkmuffinere 29 minutes ago||
I appreciate that you give actual criticisms! That's IMO much better than saying "I ignore this because it was written by AI", because it doesn't add to the conversation. So with that context, I'd like to point out where I disagree with you:

1. "We aren't discussing anything" -- I don't know, I feel it does give a summary of the paper, which is a kind of discussion

2. "It's not a good summary" -- is it not? I think this section is essentially the correct conclusion: > Even without high blood sugar or cholesterol, their muscle metabolism was already failing. They were burning less fat, generating more oxidative stress, and clearing lactate poorly—evidence of inefficient, stressed mitochondria. These are likely to be the earliest findings in people who will develop metabolic disease states such as diabetes, fatty liver, hypertension, heart disease, etc.

...

> San Millán puts it bluntly: sedentary people are not the control group. They are already metabolically impaired.

3. I don't think I know enough about to comment on the GLUT4 thing, but I do feel that's kindof in the weeds. The main message is still true I think.

4. "it's blatantly using this paper to promote his brand" -- Maybe I just don't mind him building his personal brand. I think that's what the vast majority of blogging is. I don't even see a clear sales pitch on the page, so I'm very happy with this.

Insanity 2 hours ago||
But how do you know if you exercise enough?
pton_xd 2 hours ago||
According to the linked paper [0]:

"

- Sedentary (SED): Does not perform exercise regularly or elevate heart rate outside of daily tasks

- Active (AC): Performs aerobic exercise for at least 150 minutes per week, and has at least a six-month history of doing so

"

A more comprehensive study that determines the optimal amount of exercise per week to achieve peak cellular function over a population would be quite interesting. Also, what about anaerobic exercises like weight lifting? What's the relative impact on metabolic function? Lots more to explore here!

[0] https://www.biorxiv.org/content/10.1101/2024.08.19.608601v1....

strken 2 hours ago|||
I find this a bit confusing. If you're doing an hour of HIIT a week and additionally work as a removalist, a picker in a warehouse, or a white-water rafting instructor, you're sedentary? Or is there some middle group that was excluded from the study?
CGamesPlay 36 minutes ago|||
Seems like there's a middle group: "subjects…were assigned a research arm based upon meeting one of the following criteria related to physical activity" directly precedes these groups.
ip26 1 hour ago||||
I assume “daily tasks” has been defined before. Taking the trash to the curb or walking from bedroom to kitchen, daily task. Saving your client from drowning in dangerous rapids after they capsized, not daily task.
koolba 1 hour ago|||
What warehouse worker is doing HIIT? I’m not saying they’re sedentary, but there is no way a warehouse worker is moving at the pace of a HIIT workout, let alone for an entire shift.

There’s no job on the plan outside of drug runner that requires you to actually “run”.

eru 1 hour ago||
> There’s no job on the plan outside of drug runner that requires you to actually “run”.

Drug runners don't really run either, do they? But athletes do.

xgulfie 1 hour ago|||
That "outside of daily tasks" addendum is killing me. What task performed regularly during the day is not a daily task???
pinkmuffinere 2 hours ago|||
+1. I surf occasionally, and go rock climbing a couple times a week. Compared to the "average American" I suspect I'm pretty active. Compared to other rock climbers and surfers, I'm probably relatively inactive. If I'm not concerned about improving at these hobbies, and just want 80% of the health benefit of being active, am I achieving it? Or am I still below?

Edit: From the linked paper:

'''

2.1 Subject Recruitment Nineteen male subjects ((41.9 ± 13.8 years; 82.6 ± 13.9 kg)) participated in this study and were assigned a research arm based upon meeting one of the following criteria related to physical activity:

- Sedentary (SED): n= 10. Does not perform exercise regularly or elevate heart rate outside of daily tasks

- Active (AC): n=10. Performs aerobic exercise for at least 150 minutes per week, and has at least a six-month history of doing so

'''

I bet that "Performs aerobic exercise for at least 150 minutes per week" is related to some standard advice (but I'm too lazy to confirm that. I guess that provides an easy measuring stick to decide if we're being 'active enough'

justinator 14 minutes ago|||
Health is not the same as performance. You can have the former (sounds like you do to me), without the latter (but you're working on it -- what's the rush, going to the Olympics any time soon?).

The extreme of "performance" is rarely healthy.

Insanity 1 hour ago||||
I am in a similar boat as you. I go bouldering twice a week for about 2h per session, I swim once a week for 45 minutes, and I walk an hour each day during my commute.

But I would be interested to know how much this contributes to keeping me healthy.

solraph 2 hours ago|||
The paper indicated the Active group has doing at least 150 minutes of moderate-intensity physical activity throughout the week, or 75 minutes of high intensity activity activity (matching WHO guidelines[0]), and have done so for at least six months.

Anecdotally, I and several other people have found smart watches good for keeping track of intensity minutes.

[0] https://www.who.int/initiatives/behealthy/physical-activity

justinator 16 minutes ago|||
Can you look in the mirror without feeling ashamed?
UltraSane 1 hour ago||
The best indicator of fitness is your VO2 max value and this can be estimated using fitness trackers and smart watches. You should try to be in the top 10% for your age bracket. The higher the better as all cause mortality decreases as VO2 max increases.
rootusrootus 1 hour ago||
My gripe with VO2 max on my Apple Watch, at least, is that Apple has dozens of different workout options, but none of them include the option of changing your body weight. So my VO2 max was climbing steadily until I added rucking to my workouts, and now it's been dropping. Nowhere do I have the option of telling the watch that I'm intentionally carrying extra weight. This should be trivial to add into the UI and factor into the calculation.
g-nair 1 hour ago||
I thought I was alone in this gripe but I’m happy to see someone who’s experienced the same! For my longer runs, I’ll wear a hydration vest. It seems to have an impact on my Average HR due to the added weight, and I will always see a little drop off in my VO2Max estimation as a result. A bit of a bummer :)
UltraSane 59 minutes ago||
You can set your weight to your total weight including accessories. But it might skew other values like body fat percentage.
storus 1 hour ago||
How about boosting mitochondria via supplements? Would that be something to look at? I climbed out of ME/CFS-like neurocovid mainly thanks to boosting mitochondria as much as I could and am wondering if the same lesson could be applied here?
justinator 13 minutes ago|
How about just moving around for 30 minutes most days?

Supplements aren't going to help you mentally as a nice walk in the park.

storus 1 hour ago||
Would 8 minute HIIT a few times a week do the job?
solraph 1 hour ago|
tl;dr; Nope.

Assuming that HIIT workouts are 100% vigorous activity (unlikely), then a "few" instances would only add up to around 24 minutes of vigorous activity, which is far short of the minimum recommended 75 minutes of vigorous activity.

If you are short on time then performing HIIT for 15 minutes five days a week will get you much closer to the minimum requirements.

generalenvelope 29 minutes ago|||
Vigorous activity is defined as something like > 75-80% max heart rate, or > 6.0 METS, not as an absolute, all out sprint. It's actually quite far from what you expect
storus 1 hour ago|||
4-minute HIIT run (30s full/5s walk, repeat) makes you vomit and not feel your legs. 15 minutes of HIIT 5-times a week is a wishful thinking. It's not your typical "vigorous" activity. At my athletic very best I could at most chain 3 HIITs in a row and be destroyed for a few days.
frmersdog 2 hours ago||
Sumo wrestlers generally don't develop metabolic disease until after they retire, which comes with the cessation of their grueling, multi-hour daily training regimens. I wish I could find the NHK report on a group of scientists that were researching how metabolically-undesirable substances build up in muscles after as little as 20 minutes of inactivity.

This is the one thing that makes me so angry about the state of AR/VR/XR. Human bodies are made to move when we work - not strenuously, not non-stop, but consistently and with some amount of vigor. Spatial software design represents an AMAZING opportunity to re-tune digital work processes to be movement-oriented, while still productive and efficient. Compare digital sculpting in ZBrush and Media Molecule's Dreams.

It's maybe harder to envision a similar transformation for people dealing with data or communication for a living, but is it out of the realm of possibility? It shouldn't be, for anyone who who might compare common GUIs to interfaces like VIM and Emacs. The former are the unhappy compromise between the latter and the as-yet-to-be-created spatial interfaces that would be coming if the Bigs would stop trying to outmaneuver each other, and just create them.

I am tired of trying to manage my photo library on a small laptop screen or monitor, with a single pointer. Let me summon them to my physical space and manipulate, stack, sort them, and more, with split controllers or my actual hands. I promise that my brain and body and your wallet will be much, much happier.

skeledrew 1 hour ago|
I like the reenvisioning thoughts here. We're well overdue a Minority Report style upgrade to our I/O peripherals, with keyboard and mouse being relegated to backup use.

We have/had a few things which could help (Leap Motion controller, Kinect, etc), but it's really hard to imagine how to generalize interfaces for these new device forms so they're at least on par with the old from a productivity perspective. Otherwise, people outside of research and maybe gaming won't really be sold on it.