20 October 2011

Caloric Restriction and Immunology

I know it's not particularly relevant to any disease being discussed in class right now, but I was doing some research on caloric restriction (CR) and found an interesting link between CR and immunology:

Caloric restriction (CR) is defined as a decrease in what an organism would consume ad libitum, but still above the level of malnutrition. It is arguably the most robust means of extending lifespan and has been shown to boost longevity in a wide array of organisms, ranging from yeast to rhesus monkeys. A few studies have analyzed the effects of CR on the immune system, which is known to decline with aging [1].

Given that Type 2 Diabetes is associated with inflammation that worsens with time, one such study analyzed the development of inflammation in liver, muscle, hypothalamus, and adipose tissue during aging and CR. Expression of inflammatory cytokines (TNFalpha, IL1-beta, IL-12B, and IL-6), macrophage and TLR4 markers (CD11c, CD11b, and arginase1), and proteins involved in the recruitment of macrophages (MCP-1, CCR2) were all analyzed as a function of age and CR. Interestingly, most of these markers were shown to decrease in response to CR [2]. The aging cardiovascular system is also greatly benefited by CR, with reported reductions in both inflammation and oxidative stress [3]. Some evidence also exists that CR may help to prevent/alleviate some chronic inflammatory disorders such as periodontal disease [4].

Whether or not CR mediates its effects on lifespan through significant regulation of the immune system has yet to be determined, but it's certainly an intriguing area of research.

1. Fontana L, Partridge L, Longo VD. Extending Healthy Life Span - From Yeast to Humans. Science 2010; 328(5976):321-326.
2. Horrillo D, Sierra J, Arribas C, Garcia-San Frutos M, Carrascosa JM, Lauzurica N, Fernandez-Agullo T, Ros M. Age-associated development of inflammation in Wistar rats: Effects of caloric restriction. Arch Physiol Biochem 2011; 117(3): 140-150.
3. Weiss EP, Fontana L. Caloric restriction: powerful protection for the aging heart and vasculature. Am J Physiol Heart Circ Physiol 2011; 301(4):H1205-19.
4. Gonzalez O, Tobia C, Ebersole J, Novak M. Caloric restriction and chronic inflammatory diseases. Oral Dis 2011; doi: 10.1111/j. 1601-0825.2011.01830

5 comments:

  1. I think this is really interesting, and I was looking at a few articles that said something similar a few days ago as well. I was specifically looking at alternate day calorie restriction; restricting food on one day and eating ad libitum (as much as you want) the next. This evens out to actually no CR at all, but still presents the benefits of CR.

    One of the studies showed improvement in insulin resistance, asthma, autoimmune diseases and osteoarthritis; all of which have an inflammatory component. They also noted general improvements in inflammation markers and oxidative stress.
    http://www.ncbi.nlm.nih.gov/pubmed/16529878

    Another study on alternate day CR found similar improvements in asthma, TNF-a levels were reduced to 30% of normal, and BDNF (another inflammatory molecule) was reduced to 50% of normal. They also found reductions in ceramides, lipids formed in response to inflammatory cytokine receptor activation and oxidative stress.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1859864/?tool=pubmed

    I think that CR is a novel, effective way for treating inflammation, among many other disorders. However, following a lifelong dietary restriction is very hard for most humans to adhere to, as they are constantly hungry. I believe the real potential will come with drugs that mimic the effects of CR.

    SBrookshire PSIO495K

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  2. Interesting post. Currently there is a large amount of research regarding the function of the adipose cell as an active endocring organ as opposed to simply a storage cell for fat. The adipose cell actively secretes IL-6. Research has demonstrated a correlation between BMI and elevated levels of IL-6 with obese individuals exhibiting higher levels. Increased levels of IL-6 are thought to produce a state of low grade inflammation. A sensitive marker to inflammation in the body is C-reactive protein (CRP). Elevated levels of CRP have been correlated with obeisty and subsequent cardiac disease and type II DM.

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  3. Sbrookshire:
    I completely agree with you - I think CR is really only feasible for hardcore ascetics. Most people, including myself, don't have the willpower to put themselves on the brink of starvation day after day (or on alternate days as you said, which still provides CR benefits) to be healthier. Drugs that mimic the effects of CR without actually requiring harsh dietary restrictions would be ideal.

    SharonR7630:
    That would definitely make sense. If on one end eating just enough to stay off starvation lowers inflammation, eating too much (obesity) should worsen inflammation. It also makes sense that CR would prevent disease and obesity would put someone at higher risk for disease.

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  4. I think that we need to be careful when suggesting a drug to mimic CR. It seems like just another 'quick fix' for a poorly informed public. It might be unrealistic to expect individuals to maintain harsh dietary restrictions; however, this seems to be great additional evidence supporting the maintenance of a healthy, low BMI index through dietary and physically active interventions.

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  5. From personal experience I feel as if I have been through something similar to CR. Every year our sports nutritionist advises us to lose weight once our Swimming and Diving season begins. She always gets in a bind with our weight trainer as he is not one for a caloric restrictive diet as it can impede recovery and lead to muscle loss. I usually consume somewhere between ~6,000 - 7,000 calories within 5 meals/snacks a day and she had me down to 2,200 calories with 4 meals/snacks a day (skipping a snack after 8 P.M.). Honestly it felt like I was starving. We sometimes refer to these "diets" as crash diets because your body literally feels like it's about to crash. The first week or two are the hardest by far but once you get over that hump you actually feel great. Mind you we are also supplied multivitamins and covered all the essential nutrients we needed.

    I remember being in a better mood, less foggy, and less groggy... I even stayed awake in classes (after the first 2 weeks; sometimes I couldn't make it through these weeks and dropped the diet altogether). As for the inflammation aspect of it I can't really say since I really have no idea what is going on in my body. I did however lose muscle and along with it strength but surprisingly my recovery time after training was much faster... possibly due to the fact that I had to deal with less muscle mass to tend? or maybe because my body was in a "less inflamed" state due to my restricted diet?

    I have always been a fan of food. I love everything about it except for the McDonalds around the corner. I'm also a big advocate of "you are what you eat" so basically I believe that there is a better correlation between the certain types of food you eat and inflammation rather than CR and lower inflammation though I'd have to look into it more deeply. If any of you are interested you should check out this new "fad nutrition diet" going around called the Paleo diet (Paleolithic Diet). Some medical experts are basically saying we should eat the way cavemen did so many years ago, our diet has changed so much since then that our body is basically amassing an army to combat all the nonsense contained in modern day food. Here's one website to probably start you off . . . http://thepaleodiet.com/ Enjoy!

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