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Calorie Restriction Reduces the Inflammation Associated with Arterial Aging

The practice of calorie restriction slows aging across the board. Near every known measure of aging is diminished in calorie restricted mice, and it produces significant health gains in humans. While the short term benefits of calorie restriction are quite similar in all mammals, the long term gain in life span is only large in short-lived species. Understanding why this is the case will require a near complete understanding of cellular metabolism as a whole. Researchers can pinpoint key controlling mechanisms, but the interaction between cellular metabolism and the pace of aging is enormously complex, and far from fully mapped. This is one of the reasons why progress towards calorie restriction mimetic drugs has been so painfully slow and expensive.

The example here is one of many in which calorie restriction is shown to reduce the extent of an issue that accompanies aging. Chronic inflammation is a dysregulation of the immune system and associated signaling that has serious consequences over time, accelerating the progression of all of the common age-related conditions. It is particularly damaging in the context of blood vessel walls, where the immune cells known as macrophages gather in attempts to clean up the deposits of cholesterol associated with atherosclerosis. Inflammation is well known to speed up the growth of the atherosclerotic plaques that ultimately cause a stroke or heart attack. Less of it is a good thing.

Aging exponentially increases the incidence of morbidity and mortality of quintessential cardiovascular disease mainly due to arterial proinflammatory shifts at the molecular, cellular, and tissue levels within the arterial wall. Calorie restriction (CR) in rats improves arterial function and extends both health span and life span. How CR affects the proinflammatory landscape of molecular, cellular, and tissue phenotypic shifts within the arterial wall in rats, however, remains to be elucidated.

Aortae were harvested from young (6-month-old) and old (24-month-old) Fischer 344 rats, fed ad libitum and a second group maintained on a 40% CR beginning at 1 month of age. Histopathologic and morphometric analysis of the arterial wall demonstrated that CR markedly reduced age-associated intimal medial thickening, collagen deposition, and elastin fractionation/degradation within the arterial walls. Immunostaining/blotting showed that CR effectively prevented an age-associated increase in the density of platelet-derived growth factor, matrix metalloproteinase type II activity, and transforming growth factor beta 1 and its downstream signaling molecules, phospho-mothers against decapentaplegic homolog-2/3 (p-SMAD-2/3) in the arterial wall. In early passage cultured vascular smooth muscle cells isolated from AL and CR rat aortae, CR alleviated the age-associated vascular smooth muscle cell phenotypic shifts, profibrogenic signaling, and migration/proliferation in response to platelet-derived growth factor.

In conclusion, CR reduces matrix and cellular proinflammation associated with aging that occurs within the aortic wall and that are attributable to platelet-derived growth factor signaling. Thus, CR reduces the platelet-derived growth factor-associated signaling cascade, contributing to the postponement of biological aging and preservation of a more youthful aortic wall phenotype.

Link: https://doi.org/10.1161/JAHA.118.009112

Comments

CR is conceptually simple and yet extremely hard to follow for most of the people. I would guess that high-calorie diet not only promotes the inflammation but the higher blood sugar lead to arteries stiffening (and inflammation too), and probably more thing. So if there was a magical small molecule to reduce internal inflammation the results would be remarkable, but still worse than a serious CR or intermmittent fasting

Posted by: cuberat at November 2nd, 2018 3:59 PM

There is an article (sorry I can't remember the reference) that asserts that CR is ood for all the parameters except for lynphocytes. They litterally drop after prolonged CR. Sepsis was cited in the article as an example because it's well known that the probability to survive is highly correlated to the body mass.

Posted by: Marco at November 2nd, 2018 7:25 PM

I have SBS, so CR is my modus vivendi whether I like it or not. I get no parenteral nutrition because the healthcare system in the Netherlands is so bad that (a) I get no compensation from my insurance for buying supplements or vitamins needed for treating my condition, (b) doctors have no idea what my rare disease means and (c) doctors in the Netherlands consider my low blood values alright, they do not wish to take or advise any preventative measures. I am on my own for that reason, and I need to fight every day, despite being exhausted already before the day starts, to get all the nutrients I need. I have managed to avoid anorexia so far, but I am afraid that I border on malnutrition. I am trying my best to be my own doctor and take the best care of myself, because I want to live indefinitely - I have no desire to die even when I suffer all sorts of pains my condition. I have always pondered the medical question whether my SBS is a blessing or a curse based on what we know about CR: Is it good that I cannot absorb/consume as many calories as before or is it a bad thing since my body is less efficient? I think my daily exhaustion is not exactly conducive to a healthy lifedtyle since I lie in bed a lot, but I like to think SBS will lengthen my lifespan significantly, or at least that's my hope and it may be pure fantasy on my own part. Either way, I'm trying my best every day to hold on and reading this site encourages me philosophically, I really hope you guys succeed and that I can afford the treatments.

Posted by: Purely Biological at November 2nd, 2018 9:23 PM

Hi Purely Biological ! Just a 2 cents.

I wish you lots of health improvement ! I can only imagine this must be a nightmare. From the study below it seems that malabsorption is the largest problem with lacking a long bowel, but from the results, people with SBS intake more nutrients/minerals to compensate for the lacking/malabsorption in the short bowel, so in the end this lacking is offset by consuming more nutrient, it is nearly equal as someone with no SBS who will need less nutrient intake because of maximal absorption for having the long bowel. The only major visible problem is calcium/magnesium retention/absorption, intaking more did not necessarily change things all that much has they showed BMD (bone mineral density) reduction and why these people are 'small' (there is not enough mineral deposit in the bone during their adolescence to promote full growth and obtain a bigger bone skeleton; thus, they end up smaller then they people without SBS). I think this will also reduce IGF (which is crucial for fitness and growth), but thus frailty. SBS may cause frailty, anemia, tiredness (as you are experiencing, it is normal with SBS to sleep so long (10-15+ hours) because you are working with a nutrient-starved body. I would not suggest you to overtly do CR, you reallly need your nutrients and CR is very depriving and hard on the body (I have atherosclerosis and CR is not something for me, at the start at least, now ok, but it is very taxing because my body becomes ketonic and extracts every ounce of fat on my very non-fat body (skinny, 125lbs 5'10''); as such it is like asking someone very thin/skinny nearly anorexic to give 'more' fat...when there isn't any to give on a very frail body to begin with. I have tried to gain weight but is is a Very tricky thing with my disease, it can promote the disease; thus, I understood that I have to simply 'maintain' a certain weight, not go under, neither go above (as both create serious complications and strain), your body has tried to adapt to your SBS and did a fair job, but you still suffer nutritional lackings and feel extremely tired (it makes sense that regular people will sleep 7 hours while you would sleep almost 15 hours; it means 50% the nutritional profile; you need to work at it 'double' to everyone due to SBS creating malnutrition/malabsorption). The best recourse is to make sure you intake more than enough nutrient to compensate. From the studies you could live a full life, but elderly people who have SBS at their age have high mortality...but being young and having had child SBS is different, your body adapted and thus you are far more likely to outwit/survive this. If living a life in malnutrition and malabsorption, then yes, life will be shortened; lacking nutrients is a serious problem that can affect aging/speed of aging towards acceleration (down to epigenetic methylation clock). But, if you do get your nutrients, then this acceleration should be staved off if completely stopped. People with deficiencies can developp (much later) serious complications and diseases, making them frail much quicker in old age; and thus, die quicker. To live 120 years old, you have to be is Extremely Perfect condition for Years, it is That Rare; otherwise, most with problems in their life, will reach 100 years old or less; many not more than 80 or 70 or 60 when certain big disease appears then. The more you control it (and make sure you have adequate nutrient intake/correct weight and not feel ultra-tired all the time, do your best to cut down on sleep and aim for 7 hours (7 hours is the gold mean, mortality rises if only sleeping 5 or 6 hours; while sleeping 8 hours or more also rises mortality because people die of apnea 'in their sleep' the longer they sleep; you must awake and I understand that you would feel tired and Needed More sleep like 15 hours; but sleeping such long time is a danger when not being a child anymore (such as sleep apnea or complications from sleeping too long; if you could aim for 10 already that would improve your chances)) the best you will put your chances to defeat SBS and allow you to live 100+. I hope you succeed too and wish you well. : )

Just a 2 cents.

1. https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/longterm-impact-of-infantile-short-bowel-syndrome-on-nutritional-status-and-growth/BB449C1D200C13F2D1099F49FEB23297

2. https://www.ncbi.nlm.nih.gov/pubmed/10483909

Posted by: CANanonymity at November 3rd, 2018 11:24 AM

Hi CANanonymity,

Thank you so much! Wow, you really provided a lot of information. Exactly what I was looking for. I will save your message in the SBS folder on my computer. I need to find more practical info that will help me cope with my SBS. That is why I am on this site. I really hope anyone can provide me with the latest interesting studies/information so I can extend my life and live a healthy lifestyle. I was 18 when I had an intestine surgery in 2013. More than half of my small intestine was removed, leaving me with SBS. I have no stoma fortunately. I had really bad luck to have so much of my small intesine removed, but could I still reap some benefits from "adaptation" if I was 18 at the time?

Posted by: Purely Biological at November 3rd, 2018 2:54 PM

You're welcome ! : ). Just a 2 cents,

I would think yes because 18 is really the entry into adulthood, but it is still teenage-hood (eigh-teen), the fact that it happened early like this is a very good sign (as the study showed that having 'late SBS' in very old age is much more fatal, understandably so by being old, nutrient less absorbing and frail already from old body), even if you had it at 18 it is still technically (older) 'child'/old teenager ratehr than an aged adult of many decades. Thus, the possibility of rehabilltation and rapid adaptation is bigger at early young age where the body has not accumulated sufficient residual damage to make it really consequential. But, as specified, when you do have these disease early - you can adapt to them - or not, meaning they 'stay' with you and cause complications much later. But, the degree of these Later complications depends on well you adapted this disease years previous to them appearing - thus, your entire life 'management' of this disease you had early. The better the management and (thus adaptaition) the better your 'later' chances that complications won'T happen or much later/be post-poned to about the equal of a regular disease-free life. So now we are roughly 6 years after that, thus if you managed well in these 6 years it is a Very good sign, and you must continue 'to improve' on your health; you will thank yourself/your health because you will add years in your life (or as Abraham Lincoln said: add life in your years...''It is Not the (number) Years in Our Life that Matters..but The Life in Our Years''. (I agree but you do need a certain 'Amount' of years though : ), living 5 years in bliss, is great but still just 5 years that will go so fast you won't even notice it and then it'S gone...that's why if you want to Add Years (many), you must start now (check nutrition/cut sleep/find ways/learn, the saying is: ''Your body is a temple...take care of it (you don't want a decrepitting temple, do you?)''.

Posted by: CANanonymity at November 4th, 2018 7:39 PM

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