They haven’t studied exercise injuries?

If these all actually worked, I'd presume that there would have been a study on the miraculously healthy 80 year old mice. As it stands I have to assume that most of these mouse studies are fundamentally flawed to begin with and we simply don't check for adverse reactions/overlapping mechanisms/long-term maladies.

I feel like it's once a week that HN surfaces some incredibly overhyped, low-on-the-hierarchy-of-evidence (https://en.wikipedia.org/wiki/Hierarchy_of_evidence) study specifically related to anti-aging.

I wish there was some nuanced line for science journalists to not hyperbolize about nothingburger studies in dire need of replication while also making the science exciting, slow of a process as it is. Maybe every article includes a history of the that very specific and narrow sub-branch of the field? That would be really interesting to read, and to have a gauge on how far we've come.

this is not a data point that confirms that exercise and lifting is good for you. think of it like telomeres: they give you a choice, "cancer or youth, pick two or don't play"

science like this is very useful like one puzzle piece is very useful: only in the context of many other puzzle pieces, but they're also jumbled together from many different complete puzzles.

If you can why not test that probability? You might get a surprise.

There are some signs that heat stress hormones may protect against Alzheimer’s.

They studied a family in which early onset Alzheimer’s was strongly prevalent. In the subject’s family tree, 32 cases, but he was older than his deceased relatives at the time they developed symptoms, despite carrying the markers. The only thing they could track down was that he had an elevated level of heat stress proteins in his blood and brain, and they seemed to be slowing down plaque buildup. More study needed.

Pure speculation on a few possible explanations (noting that TFA describes ordinary exercise as generating enough squishing force, any other actions the researchers did being to isolate the causal factor):

1. Mammals don't naturally exist in environments where exercise isn't mandatory. _Some_ system had to generate those compounds, and there was never any pressure to keep it from being tied to the other stress-related changes bones undergo (like density changes). Once it evolved once somewhere in some critter once via that machinery, the advantage was large enough that it was locked in.

2. Exercise directly contributes inflammatory factors. Tying the cure to those to a measure of exercise intensity (bone squishing) helps calibrate the dosage. Even if an imperfect measure, the proxy of bone loading might confer some advantage in, e.g., not wasting energy on unnecessary proteins.

3. Exercise indirectly suggests a resource-poor environment, leading to lower chance of offspring succeeding and needing longer lives to produce enough viable offspring. The compounds in question aren't free to produce, so there's an advantage in only providing them to organisms who will meaningfully benefit. Mind you, resource-poor environments often promote shorter lifespans and faster growth cycles as an evolutionary trait, _but_ without a mechanism to force your offspring to mature more quickly the osteocyte-mediated lifespan could allow for resource-dependent lifetime offspring counts.

4. The mechanism could have evolved for unrelated reasons, perhaps directly contributing to the bone density calibration osteocytes already mediate. Any impact on lifespan is incidental or otherwise produces less evolutionary pressure for or against the feature than the direct purpose of the compounds.

5. More than having evolved for unrelated reasons, the fact that the compounds have any effect at all might not be evolutionarily selected for. We produce plenty of unimportant metabolic byproducts that we don't particularly care about, and it could be that some more important osteocyte function incidentally produces these "waste" proteins.

The skeleton is economical:

Repair pays off only when the skeleton is used -- we can invest in repair because we know the animal is active/foraging and we will get paid back on the investment.

Low loading is a sign that we should cut back on maintenance -- the animal is sick, injured, starving etc and it's better to conserve energy.

The optimal amount of exercise is what tells your body to invest in repair, without acquiring repair debt. Sedentary life is the misleading signal, because it tells the body you're declining when you aren't.

> In which situations a normal mammal find its bones squished (but not crushed)?

Running, exercising, etc.

I live in a ski town. Every day, particularly in winter, provides opportunity for expending effort. I don't have kids, but my friends do, and a decent amount of my efforts at least amount to teaching them how to ski and shoe and whatnot (and generally mucking around).

Given two tribes, one where their elderly are contained at home, and another where they're wandering and learning and teaching, I guess I could see a hypothetical fitness function.

I can't imagine it's too strong, though. A simpler, more-mechanical explanation may make more sense: when you stress bones, you set off all kinds of repair processes, many of which have systemic effects.

In the article they mention exercise. Basically your muscles squish your bones while you do physical activity.

What evolutionary pressure led to that? If I have to guess animals that were still able to hunt/move/... for longer were also able to mate for longer.

I don't know if any bodily phenomena are so easily explained. The insides of a single cell are insanely complex, and to try to apply a singular causal explanation to macro phenomena seems implausible.

For me, a more interesting question is that if our bodies can arbitrarily slow down aging by releasing proteins, why wouldn’t they just do that?

Maybe there is some evolutionary trade-off behind it?

God damn it Jim, I'm a calcium rich biological structure, not a doctor!

thank mr skeltal

for good bones and calcium

You're welcome, booth

You've inspired me, I'm gonna get a lot of massages and eat more pork stock.

Knee cartilage goes fast. That’s why we have water aerobics.

I wonder if that explains the benefits of walking, despite being a light activity. Also the paradoxal fact that being slightly overweight appears to decrease mortality.

Hopefully the researchers have controlled for the saunas and cocktails that the mice were also receiving

The feline purring for healing is in Margaret Atwood’s MaddAddam trilogy and I just blew it off as too fantastical, but I’m prepared to eat my words metaphorically speaking.

> perhaps checking people that worked with pneumatic hammers or other vibration exposed workplaces.

Those probably add too much variance. For example, someone working with pneumatic hammers likely works in construction and has a likelier chance to also be exposed to harmful dust, or being in the sun a lot, or getting injured on the job. It may also be that too much vibration (too long and/or too strong) would be harmful.

After a broken foot, my mother was prescribed a vibrating Bone Healing machine. I thought it might be placebo, maybe not.

Pneumatic hammers hurts you hands/fingers, if you’re exposed to too much of it.

See https://en.wikipedia.org/wiki/Hand_arm_vibrations

Isn’t it the case that the average size of an organism (at least in mammals) correlates a lot with lifespan and cancer rate?

Elephants and whales get cancer much less than humans and humans get it much less than rats. If cancer mutations are a dice roll than the more cells an organism has the more “will I become cancerous” rolls happen, so larger organism had to evolve better mechanisms to kill cancerous cells before they get out of control.

Cancer is known to be an entirely metabolic disease. Aging, likewise, is a metabolic failure (either implicitly or by natural design ie evolution, for whatever reason). Restoring metabolic function of cells always deages them. Restoring metabolic function of cancer cells always "decancers" them, for instance transplating mitochondria from a cancer cell to a healthy cell or viceversa. Curing aging necessarily cures cancer.

What do people even mean by "curing cancer", "curing aging", it's not like a single thing in the first place

If true, Jackie Chan would still look 37yo.

It's not quite vice grips; I had to dig into the paper to understand it. Their specific DTAL protocol provided "moderate mechanical loading" of "2 N at 2 Hz for 300 cycles, twice/week, [for] 3 months". For reference, a 200g stationary object exerts that much force on a surface due to gravity. With 300 cycles at 2Hz, the exercises lasted for 150 seconds, or 2.5 minutes, and the exercises occurred twice a week.

Note, however, that their experimental model section says they applied axial force (think columns, not joists) to the tibia using an ElectroForce 3300 (https://www.tainstruments.com/3330-system/) while the mice were under anesthesia. From this, it seems like they knocked out the mice and placed their legs underneath a mechanical ram to apply axial compressive forces.

Because people are typically awake when exercising, given that muscles are designed to carry forces around the skeleton, I imagine, even after scaling from a mice to a human purely by sizing, the human force equivalent will be many times higher.

If you're looking to try this out for yourself, the seated leg press will most closely simulate the study's method. Figure out what "moderate" loading is for you, and shoot for 3 sets x 10 reps at least twice a week. Overall, choose skeletally-compressive exercises where you're "pushing," such as weighted squats (e.g. barbell squats) and any type of "press" exercise like the leg press, chest press, military press, and even cycling (you push your pedals). For the purposes of this study, avoid exercises with any pulling motion, including pull-ups, pull-downs, rows, and swimming.

From a force perspective, running has some compressive elements, but the load comes from gravity alone, and good runners minimize compressive forces. Since running therefore is primarily a pulling exercise, I can sort of see what they're getting at.

TFA explicitly calls out exercise as something which would generate those compounds. Exercise has many other impacts though, so if you're trying to isolate osteocytes as a causal factor you want an experiment which avoids interacting with those other systems as much as possible.

Lots of kinds of interactions with the physical world could potentially compress or jostle bones

Was kind of expecting/hoping for this bone song: https://www.youtube.com/watch?v=pDJKgi2e-Aw

The leg bone connected to the aging bone.

I've found standing is hard. However a treadmill desk isn't too bad. I'm not able to run while I work, but a somewhat slow walk is easy and I can do that for hours.

Time to lift weights, rather

Is that why he's measuring his bone at night... wait.

Read the paper?

Actually, this reminds me of how use of mobility devices is closely associated with mortality.

No skipping leg days...

Or break them. They might release proteins faster.

Read the article?