9 ms·

Why our waistlines expand in middle age: aging stem cells shift into overdrive

83 points by gmays 2y ago

RacingTheClock 2y ago
The more there is research into how fat actually works as a tissue the more I suspect CICO is a harmful oversimplification along the lines of just say no to drugs or abstinence-only sex education.
- simmerup 2y ago
  CICO is one of those concepts which is fundamentally correct but can cause so much pain if you follow it religiously and assume all energy sources are the same I wish I never read IIFYM when I was younger
  - contravariant 2y ago
    I think CICO works as long as you view 'diet' as part of your lifestyle rather than an activity.
  - tekla 2y ago
    CICO works perfectly well. It only causes pain because people are addicted to eating and lie to themselves about how much they actually eat. Study after study has shown that people who claim to not be able to lose weight via diet simply do not have any idea how many calories they are actually eating.
    - ivape 2y ago
      Right, no one will beat CICO the same way no one will beat death or taxes. It can hurt your feelings, but it's just the truth.
    - triceratops 2y ago
      > because people are addicted to eating What do you propose to do about that?
      - snkzxbs 2y ago
        [flagged]
        triceratops 2y ago
        It is an issue. Otherwise you have to file CICO into the category of knowledge that is correct but useless. Like "just read better" for dyslexics.
    - simmerup 2y ago
      Well sure. But the fact people over eat so readily is most likely down to the heavily refined food we eat that our hormones aren’t tuned to handle in my opinion. I know I was miserable on CICO as Iw as constantly going through cycles of gaining then losing lbs. Whereas once I switched to a whole food diet I no longer even need to think about the calories I eat, I just eat when I’m hungry. And I don’t even crave the cookies and marshmallows at all
    - const_cast 2y ago
      The oversimplification here is that you're assuming that over-consumption is both completely voluntary and the root cause. But it's not - it's actually a symptom. People overeat for a variety of extremely complex reasons. Mental health, stress, hormonal interactions. gut microbiome, dopamine deficiency, and on. The assumption that forcing yourself to eat less is solving the root cause is not sound, in my opinion. If you look at GLP-1 inhibitors, those appear to be a much more root cause solution. Rather than solving over-consumption, they solve the propensity to over-consume, which then solves over-consumption. What we really need to be looking at is why some people have a propensity to over-consume and why some don't. Why are some people destined to a life of constantly fighting food when others don't have to try at all and they stay thin? Just intuitive, I know this is also the case for other substances like alcohol. I've never had to struggle with alcohol and I never will. I just drink whenever and never think about it. But for some people, it's a lifelong struggle. They have to constantly be thinking about alcohol, and every time it touches there lips it's a problem. Why? Is it genes? Our environment? Psychological support in childhood?
- Jaxkr 2y ago
  Our metabolism is amazing and complex but CICO is a matter of thermodynamics. People get burned when measuring the “out” part because our bodies want to hold on to as much energy as possible.
  - jghn 2y ago
    Not just out, both directions can be tricky to measure. It is hard to say for certain how many potential kcal you're consuming are actually absorbed by the body. If you see whole corn kernels in the toilet, those kcal didn't count :) But yes. CICO is and always has been absolutely true. People are just overly reductive in how they measure both sides, and then claim that CICO is garbage.
    - nahkoots 2y ago
      Often, the whole kernels you see in the toilet aren't actually filled with corn.
    - ses1984 2y ago
      My brother: those kernels are filled with poop. It’s ok to assume that you absorb 100% of what you eat, unless you see evidence to the contrary, and no corn kernel poop doesn’t count. Frequent diarrhea, weight loss, skin rash, and basically any symptom of vitamin or mineral deficiency.
      - DebtDeflation 2y ago
        >It’s ok to assume that you absorb 100% of what you eat That's not really true. If you've ever done the keto diet, you know that your body expels unburned ketones through your breath, sweat, and urine. Protein can be used to repair structures rather than burned or stored for energy. There's also something called the "thermic effect of feeding". Your body requires more energy to process protein (20-30% of calories consumed) than it does carbs (5-10%) than it does fats (0-3%).
        codingdave 2y ago
- Jimpulse 2y ago
  You do have me intrigued, what are you general arguments against CICO? The mechanism from article really does suck, but what does that have to do with CICO? While white adipose cells are created, it's still excess calories that fills those cells.
  - stasa 2y ago
    In a perfect world where you measure and control everything 100% CICO rules. However, in the real world, different types of food cause variation both on in and out. E.g. some foods promote feeling to satiety and some foods cause some people to overeat. Diet would also affect gut microbiome which affects hormones/mood etc... If you calculate CICO, then it will still be valid. But from the practical diet approach, CICO is oversimplification.
    - tekla 2y ago
      > But from the practical diet approach, CICO is oversimplification. No, CICO IS the practical diet. Satiety, microbiome, none of that shit matters. All excuses to not properly stick to the diet. You weigh your food, calculate the macros, and that's it. Zero thought required past that. It is literally impossible to not lose weight even if you are eating nothing but 500 calories of pure corn syrup every day (Though you may feel pretty sick)
      - stasa 2y ago
        I actually said that CICO works if you control everything and weigh your food and calculate the macros. It may work for you, it works for bodybuilders, but this approach is not necessarily the best. All diets work though reducing calories. Dietary adherence is much more important. Most people are not going to obsessively weigh all their meals. And if you feel sick or hungry all the time, you are much more likely to break the diet. So, I maintain that, yes, CICO works and calories + macros is the most important. But unless you control intake 100%, then the types of food you consume affect how much you eat, energy levels and compliance. This is especially true long term (over 5 years).
      - 2y ago
- themgt 2y ago
  CICO, like most tautologies, is both definitionally true and fairly useless. Like being asked for financial advice and just saying "MIMO".
  - 31337Logic 2y ago
    I think this is the most important and practical comment of the thread. Start with this as your "baseline position" and work from there.
  - robertlagrant 2y ago
    People say it because there are all sorts of alternative theories, such as "setpoint theory" that say* that your weight is nothing to do with what you eat. * Or its proponents say it says
- Ekaros 2y ago
  CICO is same as when talking about personal finances and distilling it to earn more than you spend. Absolutely truthful statement, but pretty hard very often in practise... And don't really consider many finer points.
  - anonymars 2y ago
    Bang on. Indeed, I remember Ramit Sethi (finance blogger) making the same point (https://www.iwillteachyoutoberich.com/the-big-wins-manifesto/ https://www.iwillteachyoutoberich.com/the-big-wins-manifesto...) > As Clotaire Rapaille wrote in his terrific book, The Culture Code, “Years ago, Tufts University invited me to lecture during a symposium on obesity. Lecturer after lecturer offered solutions for America’s obesity problem, all of which revolved around education. Americans would be thinner if only they knew about good nutrition and the benefits of exercise, they told us. Slimming down the entire country was possible through an aggressive public awareness campaign. When it was my turn to speak, I couldn’t help beginning with an observation. “I think it is fascinating that the other speakers today have suggested that education is the answer to our country’s obesity problem,” I said. I slowly gestured around the room. “If education is the answer, then why hasn’t it helped more of you?” There were audible gasps in the auditorium when I said this, quite a few snickers, and five times as many sneers. Unsurprisingly, Tufts never invited me to lecture again.”
- maxglute 2y ago
  CICO just reflects that dietting is simple, not easy.
xvilka 2y ago
A possible solution would be some kind of viral therapy - a custom virus to target adipocytes. Similarly how it's done [1] to some cancer cells. [1] https://en.m.wikipedia.org/wiki/Oncolytic_virus https://en.m.wikipedia.org/wiki/Oncolytic_virus
- deleted 2y ago
  [deleted]
- hollerith 2y ago
  We already have the tech to delete adipocytes -- it is call liposuction. Reducing the number of adipocytes turns out to have adverse effects on metabolic health.
  - xvilka 2y ago
    IIRC, liposuction, just like every invasive surgery increases risks and complications significantly.
    - deleted 2y ago
      [deleted]
    - jghn 2y ago
      And liposuction doesn't work for visceral fat, which is far worse than subQ fat
    - hollerith 2y ago
      OK, but my point is that even if we could avoid surgical complications completely, significantly reducing the number of adipocytes in the body would still be a bad idea (in almost everyone).
- lapetitejort 2y ago
  Another solution is to accept our bodies as they are and not to promote unrealistic beauty standards in our media
wonderwonder 2y ago
Gaining weight and keeping it is a choice. There are a myriad of solutions some simple like diet and exercise, some more complex like TRT and glp-1 drugs. I gained a good amount of weight since I had kids, went from a healthy weight of 210lbs at 6'1 to 240lbs at 45 years old. I always worked out so I had good muscle mass but my diet was terrible, often consuming a pint of ice cream at night once the kids went to sleep. I got on TRT and compound semaglutide and now I am 215lbs with abs and in the best shape of my life. I recently benched 405lbs at 46 years old. Prior to this I could do 2 pull ups if I was lucky I can rep 10 - 15 now. My stress levels are down, my blood pressure is in a healthy range for the first time in decades. I go to the gym 5 days a week, sometimes 6 and I love it. There are always solutions, we don't have to accept a slow decay.
- j3s 2y ago
  > Gaining weight and keeping it is a choice for many people, it is not. you have enough free time, energy, and money to fix your weight issue - many people are missing at least one of these factors, oftentimes more. there are more complicating factors here too - try telling someone taking lithium that gaining weight is a choice. or birth control, or SSRIs... the list goes on. yeah, it's pretty easy for you - a middle aged wealthy guy - with enough free time to go to the gym 5-6 days a week - to maintain your weight. most people aren't in that situation.
  - wonderwonder 2y ago
    There are always excuses. Everything is too hard until you actually do it. Your argument is akin to being told that on average Women are shorter than men and then you say, well I know a tall woman. There are exceptions but the vast majority of us can accomplish this, we just don't prioritize it. You get what you prioritize.
    - tidbits 2y ago
      https://en.m.wikipedia.org/wiki/Survivorship_bias https://en.m.wikipedia.org/wiki/Survivorship_bias
01HNNWZ0MV43FF 2y ago
"overdrive" isn't a good metaphor most of the time Let's say they "hit the nitro" (not turbo!) or "floor it" or "give it the beans"
its_down_again 2y ago
The current title “How aging stem cells fuel visceral fat gain in middle age” suggests that existing stem cells simply ramp up fat production as they age. Single-cell RNA sequencing of APCs then identified a new committed preadipocyte population that is age enriched (CP-A), both in mice and humans. CP-As displayed high proliferation and differentiation capacities, both in vitro and in vivo. It should read more like "aging triggers emergence of a specific stem cell type (APCs) which drives visceral fat expansion"

83 points by gmays 2y ago

The more there is research into how fat actually works as a tissue the more I suspect CICO is a harmful oversimplification along the lines of just say no to drugs or abstinence-only sex education.

simmerup 2y ago
CICO is one of those concepts which is fundamentally correct but can cause so much pain if you follow it religiously and assume all energy sources are the same I wish I never read IIFYM when I was younger
- contravariant 2y ago
  I think CICO works as long as you view 'diet' as part of your lifestyle rather than an activity.
- tekla 2y ago
  CICO works perfectly well. It only causes pain because people are addicted to eating and lie to themselves about how much they actually eat. Study after study has shown that people who claim to not be able to lose weight via diet simply do not have any idea how many calories they are actually eating.
  - ivape 2y ago
    Right, no one will beat CICO the same way no one will beat death or taxes. It can hurt your feelings, but it's just the truth.
  - triceratops 2y ago
    > because people are addicted to eating What do you propose to do about that?
    - snkzxbs 2y ago
      [flagged]
      - triceratops 2y ago
        It is an issue. Otherwise you have to file CICO into the category of knowledge that is correct but useless. Like "just read better" for dyslexics.
  - simmerup 2y ago
    Well sure. But the fact people over eat so readily is most likely down to the heavily refined food we eat that our hormones aren’t tuned to handle in my opinion. I know I was miserable on CICO as Iw as constantly going through cycles of gaining then losing lbs. Whereas once I switched to a whole food diet I no longer even need to think about the calories I eat, I just eat when I’m hungry. And I don’t even crave the cookies and marshmallows at all
  - const_cast 2y ago
    The oversimplification here is that you're assuming that over-consumption is both completely voluntary and the root cause. But it's not - it's actually a symptom. People overeat for a variety of extremely complex reasons. Mental health, stress, hormonal interactions. gut microbiome, dopamine deficiency, and on. The assumption that forcing yourself to eat less is solving the root cause is not sound, in my opinion. If you look at GLP-1 inhibitors, those appear to be a much more root cause solution. Rather than solving over-consumption, they solve the propensity to over-consume, which then solves over-consumption. What we really need to be looking at is why some people have a propensity to over-consume and why some don't. Why are some people destined to a life of constantly fighting food when others don't have to try at all and they stay thin? Just intuitive, I know this is also the case for other substances like alcohol. I've never had to struggle with alcohol and I never will. I just drink whenever and never think about it. But for some people, it's a lifelong struggle. They have to constantly be thinking about alcohol, and every time it touches there lips it's a problem. Why? Is it genes? Our environment? Psychological support in childhood?
Jaxkr 2y ago
Our metabolism is amazing and complex but CICO is a matter of thermodynamics. People get burned when measuring the “out” part because our bodies want to hold on to as much energy as possible.
- jghn 2y ago
  Not just out, both directions can be tricky to measure. It is hard to say for certain how many potential kcal you're consuming are actually absorbed by the body. If you see whole corn kernels in the toilet, those kcal didn't count :) But yes. CICO is and always has been absolutely true. People are just overly reductive in how they measure both sides, and then claim that CICO is garbage.
  - nahkoots 2y ago
    Often, the whole kernels you see in the toilet aren't actually filled with corn.
  - ses1984 2y ago
    My brother: those kernels are filled with poop. It’s ok to assume that you absorb 100% of what you eat, unless you see evidence to the contrary, and no corn kernel poop doesn’t count. Frequent diarrhea, weight loss, skin rash, and basically any symptom of vitamin or mineral deficiency.
    - DebtDeflation 2y ago
      >It’s ok to assume that you absorb 100% of what you eat That's not really true. If you've ever done the keto diet, you know that your body expels unburned ketones through your breath, sweat, and urine. Protein can be used to repair structures rather than burned or stored for energy. There's also something called the "thermic effect of feeding". Your body requires more energy to process protein (20-30% of calories consumed) than it does carbs (5-10%) than it does fats (0-3%).
      - codingdave 2y ago
Jimpulse 2y ago
You do have me intrigued, what are you general arguments against CICO? The mechanism from article really does suck, but what does that have to do with CICO? While white adipose cells are created, it's still excess calories that fills those cells.
- stasa 2y ago
  In a perfect world where you measure and control everything 100% CICO rules. However, in the real world, different types of food cause variation both on in and out. E.g. some foods promote feeling to satiety and some foods cause some people to overeat. Diet would also affect gut microbiome which affects hormones/mood etc... If you calculate CICO, then it will still be valid. But from the practical diet approach, CICO is oversimplification.
  - tekla 2y ago
    > But from the practical diet approach, CICO is oversimplification. No, CICO IS the practical diet. Satiety, microbiome, none of that shit matters. All excuses to not properly stick to the diet. You weigh your food, calculate the macros, and that's it. Zero thought required past that. It is literally impossible to not lose weight even if you are eating nothing but 500 calories of pure corn syrup every day (Though you may feel pretty sick)
    - stasa 2y ago
      I actually said that CICO works if you control everything and weigh your food and calculate the macros. It may work for you, it works for bodybuilders, but this approach is not necessarily the best. All diets work though reducing calories. Dietary adherence is much more important. Most people are not going to obsessively weigh all their meals. And if you feel sick or hungry all the time, you are much more likely to break the diet. So, I maintain that, yes, CICO works and calories + macros is the most important. But unless you control intake 100%, then the types of food you consume affect how much you eat, energy levels and compliance. This is especially true long term (over 5 years).
    - 2y ago
themgt 2y ago
CICO, like most tautologies, is both definitionally true and fairly useless. Like being asked for financial advice and just saying "MIMO".
- 31337Logic 2y ago
  I think this is the most important and practical comment of the thread. Start with this as your "baseline position" and work from there.
- robertlagrant 2y ago
  People say it because there are all sorts of alternative theories, such as "setpoint theory" that say* that your weight is nothing to do with what you eat. * Or its proponents say it says
Ekaros 2y ago
CICO is same as when talking about personal finances and distilling it to earn more than you spend. Absolutely truthful statement, but pretty hard very often in practise... And don't really consider many finer points.
- anonymars 2y ago
  Bang on. Indeed, I remember Ramit Sethi (finance blogger) making the same point (https://www.iwillteachyoutoberich.com/the-big-wins-manifesto/ https://www.iwillteachyoutoberich.com/the-big-wins-manifesto...) > As Clotaire Rapaille wrote in his terrific book, The Culture Code, “Years ago, Tufts University invited me to lecture during a symposium on obesity. Lecturer after lecturer offered solutions for America’s obesity problem, all of which revolved around education. Americans would be thinner if only they knew about good nutrition and the benefits of exercise, they told us. Slimming down the entire country was possible through an aggressive public awareness campaign. When it was my turn to speak, I couldn’t help beginning with an observation. “I think it is fascinating that the other speakers today have suggested that education is the answer to our country’s obesity problem,” I said. I slowly gestured around the room. “If education is the answer, then why hasn’t it helped more of you?” There were audible gasps in the auditorium when I said this, quite a few snickers, and five times as many sneers. Unsurprisingly, Tufts never invited me to lecture again.”
maxglute 2y ago
CICO just reflects that dietting is simple, not easy.

xvilka 2y ago

A possible solution would be some kind of viral therapy - a custom virus to target adipocytes. Similarly how it's done [1] to some cancer cells. [1] https://en.m.wikipedia.org/wiki/Oncolytic_virus https://en.m.wikipedia.org/wiki/Oncolytic_virus

deleted 2y ago
[deleted]
hollerith 2y ago
We already have the tech to delete adipocytes -- it is call liposuction. Reducing the number of adipocytes turns out to have adverse effects on metabolic health.
- xvilka 2y ago
  IIRC, liposuction, just like every invasive surgery increases risks and complications significantly.
  - deleted 2y ago
    [deleted]
  - jghn 2y ago
    And liposuction doesn't work for visceral fat, which is far worse than subQ fat
  - hollerith 2y ago
    OK, but my point is that even if we could avoid surgical complications completely, significantly reducing the number of adipocytes in the body would still be a bad idea (in almost everyone).
lapetitejort 2y ago
Another solution is to accept our bodies as they are and not to promote unrealistic beauty standards in our media

wonderwonder 2y ago

Gaining weight and keeping it is a choice. There are a myriad of solutions some simple like diet and exercise, some more complex like TRT and glp-1 drugs. I gained a good amount of weight since I had kids, went from a healthy weight of 210lbs at 6'1 to 240lbs at 45 years old. I always worked out so I had good muscle mass but my diet was terrible, often consuming a pint of ice cream at night once the kids went to sleep. I got on TRT and compound semaglutide and now I am 215lbs with abs and in the best shape of my life. I recently benched 405lbs at 46 years old. Prior to this I could do 2 pull ups if I was lucky I can rep 10 - 15 now. My stress levels are down, my blood pressure is in a healthy range for the first time in decades. I go to the gym 5 days a week, sometimes 6 and I love it. There are always solutions, we don't have to accept a slow decay.

j3s 2y ago
> Gaining weight and keeping it is a choice for many people, it is not. you have enough free time, energy, and money to fix your weight issue - many people are missing at least one of these factors, oftentimes more. there are more complicating factors here too - try telling someone taking lithium that gaining weight is a choice. or birth control, or SSRIs... the list goes on. yeah, it's pretty easy for you - a middle aged wealthy guy - with enough free time to go to the gym 5-6 days a week - to maintain your weight. most people aren't in that situation.
- wonderwonder 2y ago
  There are always excuses. Everything is too hard until you actually do it. Your argument is akin to being told that on average Women are shorter than men and then you say, well I know a tall woman. There are exceptions but the vast majority of us can accomplish this, we just don't prioritize it. You get what you prioritize.
  - tidbits 2y ago
    https://en.m.wikipedia.org/wiki/Survivorship_bias https://en.m.wikipedia.org/wiki/Survivorship_bias

01HNNWZ0MV43FF 2y ago

"overdrive" isn't a good metaphor most of the time Let's say they "hit the nitro" (not turbo!) or "floor it" or "give it the beans"

its_down_again 2y ago

The current title “How aging stem cells fuel visceral fat gain in middle age” suggests that existing stem cells simply ramp up fat production as they age. Single-cell RNA sequencing of APCs then identified a new committed preadipocyte population that is age enriched (CP-A), both in mice and humans. CP-As displayed high proliferation and differentiation capacities, both in vitro and in vivo. It should read more like "aging triggers emergence of a specific stem cell type (APCs) which drives visceral fat expansion"