NIH Papers Say Leucine/TOR Signalling Accelerates Aging and Contributes to Diabetes, Obesity

[Ron Lambert]

 

The following two abstracts from scientific papers indicate that increased levels of the amino acid leucine, which meat and dairy foods supply in high amounts, can increase aging (reduce lifespan) by a molecular mechanism called “TOR Signaling,” as well as enhance the development of adult onset (type 2) diabetes and obesity. Please note especially the highlighted passages.

 

Quote

 

Leucine signaling in the pathogenesis of type 2 diabetes and obesity

 Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310004/

Abstract

Epidemiological evidence points to increased dairy and meat consumption, staples of the Western diet, as major risk factors for the development of type 2 diabetes (T2D). This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1 (mTORC1). mTORC1, a pivotal nutrient-sensitive kinase, promotes growth and cell proliferation in response to glucose, energy, growth factors and amino acids. Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine, a primary and independent stimulator for mTORC1 activation. The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of β-cells. Moreover, leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis, thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis. Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D, which are all associated with hyperactivation of mTORC1. In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling. Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects. Furthermore, bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids. Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity, as well as other epidemic diseases of civilization with increased mTORC1 signaling, especially cancer and neurodegenerative diseases, which are frequently associated with T2D.

 

 

Quote

 

TOR signaling never gets old: Aging, longevity and TORC1 activity

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943975/

Abstract:

The TOR (target of rapamycin) signal transduction network monitors intra- and extracellular conditions that favor cell growth. Research during the last decade has revealed a modular structure of the TOR signaling network. Each signaling module senses a particular set of signals from the cellular milieu and exerts regulatory control towards TOR activity. The TOR pathway responds to growth factor signals, nutrient availability, and cellular stresses like hypoxia and energy stress. The signaling modules and their molecular components constituting the TOR network are remarkably conserved in both sequence and function across species. In yeast, roundworms, flies, and mice, the TOR pathway has been shown to regulate lifespan. Correspondingly, genetic, dietary or pharmacological manipulation of individual signaling modules as well as TOR activity itself extends lifespan in these model organisms. We discuss the potential impact of manipulating TOR activity for human health and lifespan.

 

Someone among my email contacts to whom I sent the above has expressed the wish that my previous mailing were “written in English.” ☺

I tried to keep it simple and understandable by only using the abstracts that introduce and summarize the papers. I had to include some technical detail, because I also sent this same mailing to a number of technically trained people, including my doctor.

 

Maybe I can explain it in "English." Proteins are comprised of amino acids. There are nine amino acids that we have to have in our diet. One of them is leucine. However, extensive research over the past ten years has revealed that if there is too much leucine, it increases something on a molecular level in the cells in our bodies called "TOR signaling," which has been shown to contribute to the development of adult onset (type 2) diabetes, and also to obesity. Further studies have shown that this same mechanism also causes more rapid aging--shortening lifespan. There are certain chemicals in plant foods ("plant-derived polyphenols and flavonoids") that help to inhibit the kind of TOR signaling that causes diabetes, obesity, and accelerated aging. It is believed that by avoiding meats and dairy products, which supply leucine in high amounts, the result also will be prevention of diabetes, obesity, and rapid aging--thus resulting in extended lifespan.

So the vegans are right--we need to avoid all dairy products, as well.

Of course, we have known these things have to be true, because of the famous government-sponsored study of Seventh-day Adventists, which showed that vegetarian Adventists live seven years longer than Adventists who eat meat, and that vegan Adventists who also eat no dairy products, on average live 12 years longer than Adventists who eat meat. We always assumed that this was because of various general undesirable characteristics of meat and dairy products, like increased disease, cholesterol, etc. But now, for the first time, we have the actual, exact biochemical mechanism identified which explains why these things are so.

[Outta Here]

Can we eat eggs?

[Ron Lambert]

Eggs, being an animal product, also are contraindicated.

 

[Ron Lambert]

Here are excerpts from a partial listing of the foods highest in leucine:

 (based on levels per 200-Calorie serving

Link: http://nutritiondata.self.com/foods-000082000000000000000.html

1 Egg, white, raw, fresh

Leucine: 4233mg

 

2 Soy protein isolate, potassium type, crude protein basis

Leucine: 4226mg

[This may be bad news for soy-based meat analogs.]

 

14 Chicken, broilers or fryers, breast, meat only, cooked, rotisserie, original seasoning

Leucine: 3698mg

 

19 Fish, tuna, light, canned in water, drained solids

Leucine: 3574mg

 

22 Turkey, fryer-roasters, light meat, meat only, raw

Leucine: 3569mg

 

25 Fish, cod, Pacific, cooked, dry heat

Leucine: 3552mg

 

35 Cheese, cottage, lowfat, 1% milkfat

Leucine: 3540mg

 

[Ron Lambert]

Perhaps a fairer representation of the effect on blood leucine levels after eating certain foods is the following:

90 minutes after eating a meal, content of blood in rats tested, leucine content expressed in μmol/L:

Baseline:       84 ±4.6

Wheat:          78 ±4.3

Soy:               84 ±5.6

Egg:             146 ±8.4

Whey:          192 ±11.4

From this it appears that egg and whey (a milk product) produce the highest increase in blood leucine content, while wheat and soy maintain normal blood leucine levels.

Link: http://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-9-67

(From Table 4)

So maybe the soy-based meat analogs are OK, after all.

[Ron Lambert]

μmol/L means millimols per liter.

[Ron Lambert]

Oops, sorry, I believe μmol/L means micromol per liter.