Metabolic and cellular differences between sedentary and active individuals
39 comments
·November 9, 2025domenicd
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.
dooglius
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.
sublinear
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.
John23832
Then jog it? That's not a negative.
striking
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.
Blackthorn
People must have very different definitions of HIIT because there's no way someone is sustaining a 2 minute absolute max-effort sprint.
trjordan
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
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.
rester324
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).
striking
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.
jaggederest
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.
Madmallard
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
What illness if you don't mind me asking?
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JumpCrisscross
andy99
Probably a better link for the post, the current article appears to be an AI generated ad
pinkmuffinere
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?
storus
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?
Insanity
But how do you know if you exercise enough?
pton_xd
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....
xgulfie
That "outside of daily tasks" addendum is killing me. What task performed regularly during the day is not a daily task???
strken
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?
ip26
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
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”.
pinkmuffinere
+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'
Insanity
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.
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solraph
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
UltraSane
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
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
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 :)
frmersdog
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
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.
storus
Would 8 minute HIIT a few times a week do the job?
solraph
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.
storus
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.
null
Study: https://www.biorxiv.org/content/10.1101/2024.08.19.608601v1....