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How exercise in old age prevents the immune system from declining (bbc.com)
225 points by Luc on March 9, 2018 | hide | past | favorite | 64 comments



I've been working on a product to help families stay more connected with the elderly people in their lives, https://nanagram.co. In addition to spending a solid amount of time w/ my 94-year-old Grandpa the past couple years the project has been a fascinating journey learning about life after 80.

It's so awesome to see an 82 year old guy on his road bike in the video on this article!

Susan Pinker has a fascinating Ted talk on the secret to a long life. For years I'd always assumed things like diet and exercise would be the top factors. But according to Pinker social integration is the top factor, even higher than drinking and smoking (which, somehow, are higher than exercise).

https://www.ted.com/talks/susan_pinker_the_secret_to_living_...

This study is about endurance cyclists, showing them riding in social groups. Is exercise really the top factor here? Or is it riding in social groups? Maybe it's a combination of both.

I've seen the impact regular exercise can have on my own physical and mental health and on my Grandpa's. Past age 90, exercise can become a real challenge. At this stage, my Grandpa has a couple in-home nurses who visit and help him complete various exercises each week, lifting his arms above his head, moving his legs, etc. Other than that, I try and visit him as often as possible. We do simple things, like shop for groceries together, to keep him moving.

One of the most eye opening experiences for me on old age was about 18 months ago just after my Grandpa stopped driving at age 93. I started visiting him more and we began a genealogy project of sorts. At first his memory wasn't so great. But after a month or so of regular visits, it was like a fire was ignited. All of the sudden he was reciting incredible facts and figures about the past. He kept up with all the little details in my life better than many of the people I know in my 30s. And there was a new pep in his step. It's rare to live past 90. I'm grateful for every day I get with my grandparents, both 94 and under 30min from me. If you have an older person in your life, I encourage making as much time as possible to visit. There's so much you can learn from them and your visits can have a positive impact on their life too.


A different study found that intense exercise reverses aging at the cellular level: http://www.health.com/fitness/anti-aging-hiit-workout

The body process lymph several times more efficiently while active. This is how the body removes wastes from tissues. Seems to me that would be pertinent.


Given that this study focuses on declining naive T cell production and thymic tissue loss, it is interesting to look at another recent study that suggests these losses are the dominant cause of increased cancer rates with age.

https://doi.org/10.1073/pnas.1714478115

T cells develop from hematopoietic stem cells as part of the lymphoid lineage and have the ability to detect foreign antigens and neoantigens arising from cancer cells. In the thymus, lymphoid progenitors commit to a specific T cell receptor and undergo selection events that screen against self-reactivity. Cells that pass these selection gates then leave the thymus, clonally expanding to form the patrolling naive T cell pool.

The vast majority of vertebrates experience thymic involution (or atrophy) in which thymic epithelial tissue is replaced with adipose tissue, resulting in decreasing T cell export from the thymus. In humans, this is thought to begin as early as 1 year of age. The rate of thymic T cell production is estimated to decline exponentially over time with a half-life of ∼15.7 years. Declining production of new naive T cells is thought to be a significant component of immunosenescence, the age-related decline in immune system function. With the recent successes of T cell-based immunotherapies, it is timely to assess how thymic involution may affect cancer and infectious disease incidence.

It is clear from epidemiological data that incidence of infectious disease and cancer increases dramatically with age, and, specifically, that many cancer incidence curves follow an apparent power law. The simplest model to account for this assumes that cancer initiation is the result of a gradual accumulation of rare "driver" mutations in one single cell. Furthermore, the fitting of this power law model (PLM) can be used to estimate the number of such mutations. Exponential curves have also been used to fit cancer incidence data, resulting in worse fits than the PLM overall. Nevertheless, it is worth noting that exponential rates close to the declining curve for thymic T cell production can be seen to emerge from the incidence data, indicating the relevance of the thymic involution timescale. While the PLM fits well, it does not account for changes in the immune system with age. To better determine the processes underlying carcinogenesis, we asked whether an alternative model, based only on age-related changes in immune system function, might partly or entirely explain cancer incidence.

Our model outperforms the power law model with the same number of fitting parameters in describing cancer incidence data across a wide spectrum of different cancers, and provides excellent fits to infectious disease data. Our hypothesis and results add to the understanding of infectious disease and cancer incidence, suggesting in the latter case that immunosenescence, rather than gradual accumulation of mutations, serves as the predominant reason for an increase in cancer incidence with age for many cancers. For future therapies, including preventative therapies, strengthening the functionality of the aging immune system appears to be more feasible than limiting genetic mutations, which raises hope for effective new treatments.


>"Given that this study focuses on declining naive T cell production and thymic tissue loss, it is interesting to look at another recent study that suggests these losses are the dominant cause of increased cancer rates with age.

[...]

Our model outperforms the power law model"

Interesting, since cancer "rates" (age-specific incidence) for many cancers peak at 60-90 years old. This paper looks like they cut off the data at 85 years, ignore the peaks during youth, and aggregate the data in such a way (eg colon and rectum grouped together) to force a power law fit.

EDIT:

Also, they just say "data from SEER". What years did they use, inclusion criteria, etc?


I have a concern.

A few months ago, a widely publicized study[1] indicated that moderate-to-large amounts of exercise caused a buildup of plaque in the hearts of middle-aged white men. This correlation was not seen in any women, nor was it seen in black men.

Unfortunately, this study included no Indian nor Southeast Asian people. I've seen unrelated studies indicating similar health outcomes for white men and Indian men, so as an Indian man, should I be worried about this?

[1]: https://today.uic.edu/physically-active-white-men-at-high-ri...


Not even middle-aged white men should worry about it. It was more "This population had the highest coronary artery calcification, which matches what other studies have found. We should look into it more" rather than "These white dudes gotta slow down or their hearts'll give out".


I appreciate your response. I’m under the impression that the white men who exercised more had more calcification:

> Instead, Laddu and her colleagues found that participants in trajectory group three, or those who exercised the most, were 27 percent more likely than those in trajectory group one to develop CAC by middle age. CAC was measured during the participants’ 25th year in the study using computed tomography, a CT scan, of the chest. At year 25, participants were ages 43 to 55.


Feeling concerned about newly discovered correlations isn't going to help you live longer.

Maybe this will help you: http://tylervigen.com/spurious-correlations


You probably eat different from most white men. If you are concerned, you could look for studies that correlate dietary choices or other factors to such calcification.

Exercise is just one factor here and does not operate in isolation.


There was another study that found that thinner people and athletes ate more sugar, on average, than heavier or non-athletic people.

Since high sugar levels cause plaque buildup, perhaps that explains the correlation?


If you work at a desk all day and are interested in being more active, take a look at Desk Cycle:

https://deskcycle.com/

I got one a few months ago after reading a testimonial in a similar thread here on hacker news. Mine sits permanently under my desk. I have nothing but positive comments to say about it. Fit's nicely under the desk, works wonderfully.


Looks good for perpetual foot-tappers, too.

Would be good if it could generate power...maybe charge up a device a bit in the process.


I'd be curious to know if similar effects are observed in orthogonal types of physical activity from cycling, e.g. strength training.


I hear often that strength training is more beneficial as, supposedly, increments your growth hormone levels.

I'm also interested in a listing of publications comparing different physical activities for their fitness related to improving health overall and anti-aging concretely. ?


The publication this is based on is open access: http://onlinelibrary.wiley.com/doi/10.1111/acel.12750/full


Metformin acts on a number of hormone receptors which are also affected by Calorie Restriction for long and cancer free life https://www.economist.com/news/briefing/21704788-fight-cheat...


I don't think it's any one thing. Exercise helps people stay connected with others. Being healthy enough for exercise is important, but regular exercise also makes illness more obvious. If you stay at home watching TV then feeling bad does not change much, if you normally bike around then dizzy spells become really noticeable.


On a 5 hr bike ride your body is going to go into a similar state as intermittent fasting with all your glycogen being burned off. Similar to fasting this frees up energy and allows the garbage in your system to be burned off.


I do a ~24 hour fast weekly, and a LOT of sites go into this "burning off garbage" or "toxin cleaning" rhetoric which always puts me in "bullshit warning" mode. Is there actual science behind these claims?


The 'detox' side of it is very likely garbage (but a great way to sell); on the other hand, 5-hour bike rides without fuel will deplete your glycogen stores and there'll come a point where the differnce becomes obvious (see 'bonk-training').

A 24-hour fast is different; your body will burn fat at sufficient rate to avoid glycogen depletion (it's pretty simple; the harder you exercise the less energy comes from fat and more from 'carbs').

From a weight-less perspective though all that matters is calories out exceed calories in - it's quite possible though that fasts end up making you less hungry than hard exercise does.

Long-distance cyclists don't worry about any of this though - the approach is actually pretty simple:-

Press food to face.

Suck.

Repeat.

Edit: formatting.


In one of his articles Ray Cronise gave some numbers that even with light jogging or even fast walking for fuel body uses carbohydrates exclusively. So cardio exercises are a bad way to loose weight. They made people hungry. And as people eat all the fat from the food is stored as body fat and may not be burned until the next exercise.


That's pretty much it; although at higher intensities the calories per unit time is higher, the higher the intensity the more comes from short-term stores (glycogen) than from long-term (fat).

The numbers suggest 60 to 70 per cent of max heartrate (which is pretty easy) is the sweet spot for general fitness and fat burning (i.e. weight loss). For improved endurance, spend a lot of time in that zone; for improved performance spend shorter periods (well) above it.


The only thing I've read that doesn't completely fire off my "bullshit warning mode" is something like "fasting can enable stem cells, and have immune system destroy old cells" like explained here: https://www.telegraph.co.uk/science/2016/03/12/fasting-for-t...

Still seems a little too "high level" to actually believe though. In any case, I still do IF by skipping breakfast, mostly because I'm lazy, and after fasting for so many years hunger doesn't really bother me that much.


Fat tissue is a collector of some kinds of toxins (don't remember exactly which now) and some heavy metals (heh). Going into fat burning actually releases these into your system (which should be bad, though)



Yup that was it, thanks!


These kinds of claims when made about fasting are IME usually talking about autophagy. https://www.niddk.nih.gov/news/archive/2013/working-out-heal... is the least shady synopsis I could find. That mainly talks about exercise - for fasting, people seem to be most interested in the mTOR pathway. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266408/figure/...

I'm not qualified to judge the literature as a whole, and it appears to be an open question whether this can be translated to actionable advice, but we're not in complete bullshit territory here.


Years ago I attended a health seminar where the presenter stated that the digestive system uses lots of energy to digest food. He (and other authors I've read) suggested the idea that generally speaking, when your body doesn't have to spend energy digesting it can do other things better. (ie, detox would fit in with this) Though I can't say I understand how or why this would work, it's seems a reasonable assumption.


I read some Russian articles about research carried out about 40 years ago about the most efficient way to survive on limited food if one gets lost in wild nature. Their conclusion was that one should not ration food. One should just eat normally until one runs out of food and then fast until normal amount of food is available. And fast here means literally zero calories. One should not eat berries, mushrooms etc. Those triggers digestion that spend more energy that will be extracted from snacks.


> garbage in your system

What precisely is this?


Garbage statement. Your body is not an incinerator. Kidneys and liver take care of the garbage.


Lymphatic system, which operates during movement.


Most athletes doing long bike rides consume carbohydrate supplements such as sports drinks or energy bars. Otherwise unless you're going at a really slow pace you'll "bonk" after a few hours and be physically unable to continue.


- is it correlation or causation? - could the causation be in the other direction?

You always need to ask these questions. Perhaps senior people who have immune systems as 20-year olds, are much more likely to cycle in old age. Or there is some other reason that causes both.


Does it matter that much? Just be active for as long as possible and reap the benefits of fit muscles and a stronger heart.

Purely anecdotal: My grandfather is nearing 90 and still jumps on his indoor bike every day. Last winter he fell (due to ice) and got away with a few bruises. For other people his age this kind of fall could have meant a broken hip. He had two heart attacks when he was around 60 and a life long lung disease - far away from the immune system (or health) of a 20-year old.


Of course it matters. If the old cyclists are just genetically superior, then prescribing 100 mile bike rides to frail old people might be damaging, rather than transforming them into disease-resistant superhumans.


Why would you prescribe a 100 mile ride to an old person?

My point was that living a long and fairly healthy life is a day to day project, not a pill you take once you hit 70.


Don't be ridiculous. No physician or trainer would prescribe a century ride to a frail old person. That's something you have to work up to. But if they start with something easier then some of them will eventually stop being frail, and start being capable of completing long rides.


Does it matter? Of course logic and keeping it real matters unless you want to be ruled by superstition all your life.


I don't think the positive effects daily cardio are superstition.


Saying exercise prevents decline normalizes being sedentary.

I prefer considering exercise normal and saying its lack accelerates decline.

Anyone is free to call normal what they want, but I find my way leads me to live more healthy.


This is a great way to put it. I've been exercising so long that it is my normal. Not exercising for more than two days in a row and I start to feel weird/not healthy. This has led me to end up on the treadmill at 10pm or 5am. When it becomes your normal it is just like breathing or eating.


Same to me, but I was more active when I was living in a warm country. Now I am living in a mildly cold winter country, and struggling to go out out to walk/run because of the cold. 3 weeks and I already feeling less productive and healthy.


Check Craigslist for a cheap treadmill or stationary bike if you have room. Years ago I bought an inexpensive treadmill that had been used maybe twice, that I still use today when I can't get to the gym.


Running in the cold is great. I run outside until it gets below -20 deg C. Some thermal tights and a few layers on top is all you need. It took me quite a few years to finally just give it a try and now I actually prefer running in the winter vs summer.


There are masks you can wear that makes it easier to breath the cold air for running when it's even colder. I guess it heats the air a bit. I like walking in the cold, just have to dress for it and not overdo it so you overheat in your nice warm clothes :-)

I haven't tried the breathing masks though I probably should since I have asthma and breathing in the cold makes it worse.


I did the same comment seconds ago about breathing. I don't have asthma, but this is something that is difficult for me too.


Are they the sort of mask that makes you look like subzero from Mortal Kombat? I've been thinking about getting one.


I dont know about those, the one I saw looked like an asthma inhalator I think. But this was long ago.


Wow, this is great. I feel ashamed now because I was complaining about a 10-15 deg C cold. My old city was around 30 C the whole year.

What about breathing? Do you use any mask or this is something that you get used too?


I've never worn any kind of mask. I grew up in this weather, so maybe I'm used to. I was just in the Caribbean for a holiday. I tried running in +27 C weather with 70% humidity and I felt like I was suffocating.


I've seen people going to the park here in t-short, shorts and flip-flops the first nice day in spring when the weather goes above 10C.... ;-)


My problem with that right now is running in the snow/ice. The cold doesn't bother me, but It's hard to run on ice, even with traction devices on your shoes.


Yes, ice is by far the worst part. You have to pick your route to avoid it. I'm lucky enough to have a mostly cleared or packed paths in my neighborhood.


I think is normal ( like almost all animals) to be less active in the winter, and to be really active in the warm time/summer.

I do the same, body is used to idle in the winter/cold time. In summer, I spend almost all my free time outside.

Feeling great at my 40's.


There's a saying: You don't stop running when you become old. You become old when you stop running.

Of course, "running" can be substituted with any other exercise


Not only a saying: science. As long as you can walk 1.36 m/s (about 5 km/hour), the grim reaper will never catch up with you. 0.82 m/s (about 3km/hour) already makes you mostly safe (http://www.bmj.com/content/343/bmj.d7679)


It's nice to see an editor for the BMJ (formerly British Medical Journal) has a sense of humor. I wasn't expecting to see Pratchett T. as the first citation in a (somewhat) serious medical journal article.


The BMJ Christmas issue traditionally is for (somewhat) serious science, presented funnily. https://www.medicalnewstoday.com/articles/320319.php has some examples.


I always feel this way when i see 'anti-' something. For example anti-austerity. That noun makes it sound as if austerity was the norm and sane choice and anyone with better ideas was being negative.


It's quite obvious actually, a very neglected truth. Humans are animals and sustaining the body takes work and time, the body needs it though, all mammals have maintenance to do. It shows how much modernity is twisting some basic stuff. The problem though maybe is what other truths we'd had to take into consideration by accepting that one, mainly that our society, lifestyle, work expectations & etc literally kills us slowly.


This needs to be one of those Bear memes.. anyway I like this and will put it up on my door at work.


This is often referred to as the "normalization of deviance" in sociology and public health research.


Publicity materials: https://theconversation.com/exercise-can-slow-the-ageing-pro...

Paper: https://doi.org/10.1111/acel.12750

This age of biotechnology is also an age of comparative indolence and comfort. As the research community measures specific biochemical aspects of aging, such as the decline of the cardiovascular system, or metrics relating to immunosenescence in the immune system, we might question the degree to which the results are peculiar to our era. How much of aging is the result of our choices - to eat more and exercise less than our ancestors - rather than the result of inexorable processes of biochemical damage that we, as yet, have little influence over? (Conversely, how much of past aging was due to infectious disease, malnutrition, and other adverse external circumstances that are controlled to a much greater degree today?) This topic crops up fairly often in research into the effects of exercise on health, and the research noted here is a particularly striking example of the type.

The study authors find that the age-related decline of new T cells maturing in the thymus is negligible in some people, those who exercise much more than the rest of us. This diminished supply of new T cells is thought to be an important component of immune system aging, and the failure of the immune system is very influential over many other aspects of aging: senescent cell accumulation, frailty, loss of regenerative capacity, chronic inflammation, cancer risk, and so on. Yet when we look at the demographic evidence for spread of life span based on exercise, it appears to be, at most, 6 or 7 years (with a much larger divergence when it comes to state of health over time). What does this tell us about the likely gains resulting from rejuvenation therapies seeking to regenerate the thymus? Less than we would like, I suspect, and not just because it is hard to evaluate any one contribution to aging in isolation of all of the others.

The thymus atrophies over adult life, with active tissue necessary for the production of T cells being replaced by fat. The first major loss of active thymic tissue occurs at the end of childhood, however, in a process known as involution. Immune cells are generated at a tremendous rate in children in comparison to young adults; evolution selected for a system that would be highly effective at the outset, at the cost of later issues. When it is observed that old people in their 60s and 70s who maintained a high level of fitness throughout life exhibit much the same thymic output as young people in their 20s, that tells us little regarding the outcome were the thymus restored to the same level of active tissue as is present in children. Only a mild restoration, to move thymic activity from typical aged to typical young adult, would be comparable - and why would we stop there?




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