Saturday, November 16, 2013

Dietary Restriction: the Fountain of Youth?


Dietary restriction is based around low calorie intake. A person who practices this gets the necessary nutrients without the bulk of the calories that normally come with it.  Why would someone want to purposely shift into a negative weight balance? Well, dietary restriction has been shown to significantly delay the onset of age related disorders, including cancer, diabetes, cardiovascular disease, and brain atrophy (3).
Dietary restriction comes down to three main components, TOR (target of rapamycin), Sch9, and protein kinase A. These specific proteins are all kinases that speed up the rate of transcription in cells. It has been shown that decreased activity in these kinases slows down the aging process. Dietary restriction decreases this ribosomal production.  It does this by inhibiting TOR and Sch9 production. This in turn inhibits the initiation of transcription, which ultimately leads to longer life spans. So in a nutshell, dietary restriction causes the different kinases that are important for the initiation of transcription to be inhibited or down regulated, which ultimately causes the large-scale effect of longer life (1).
In order to determine the physiologic processes behind this phenomenon, scientists looked at ribosomes in yeast and discovered that selective mutations in these ribosomes caused increased longevity. Ribosomes can be broken down into two types, large subunits, 60S or small subunits, 40S.  Mutations, designed to inhibit parts of the ribosomes, in 40S did not seem to have an affect on life span. However, they did in the 60S subunit. This indicated that an increased life span is a byproduct of the inhibition of the large subunits of ribosomes (1). This finding was further reinforced through the use of a drug called diazaborine, which interferes with protein synthesis on 60S of the ribosome. Cells that were treated with diazaborine lived around 50% longer than cells without this treatment (2). When you inhibit the production of 60S Gcn4, a transcription factor, becomes more activated. Gcn4 is specifically tied to longevity, seeing that when the scientists inhibited Gcn4 life span decreased.  So the secret to an increased life span is a reduction in calories, which causes an inhibition of, 60S, which in turn causes an increase in activation of Gcn4, delaying the onset of age related disorders (1).
The only question remaining is how effective is dietary restriction? It turns out very. In C Elegans, a type of worm, life span was increased by as much as 50% (1). Similar findings have been reported in rats. Not much research has been done in humans yet however, the previous studies make it a very promising prospective.

References
(1) Steffen, K. K., MacKay, V. L., Kerr, E. O., Tsuchiya, M., Hu, D., Fox, L. A., & ... Kaeberlein,
M. (2008). Yeast Life Span Extension by Depletion of 60S Ribosomal Subunits Is Mediated by Gcn4. Cell, 133, 292-302. doi:10.1016/j.cell.2008.02.037

(2) University of Washington (2008, April 21). How Dietary Restriction Slows Down
Aging. ScienceDaily. Retrieved November 16, 2013, from http://www.sciencedaily.com­ /releases/2008/04/080417130533.htm
(3) Everitt, A., Hilmer, S., Brand-Miller, J., Jamieson, H., Truswell, A., Sharma, A., & ...
Le Couteur, D. (2006). Dietary approaches that delay age-related diseases. Clinical Interventions In Aging, 1(1), 11-31.

2 comments:

  1. This is a very interesting find, Matt. It actually sparked my memory of an article and video that I came across awhile ago. The article is about "Soylent", a liquid meal substitute that a young engineer came up with that is supposed to provide all necessary vitamins and nutrients to sustain someone for an entire day through just drinking one serving. The article is really focused more on solving world hunger and addressing overpopulation issues. Regardless, though, your article made me think about what the implications would be for drinking something like Soylent, with regard to increasing life span. While Soylent is surely not calorie-free, it would most likely facilitate a lifestyle of having a restricted diet. One drink probably does not contain the 1500-2500 calories that people tend to consume over the course of a day (unless they are living in a part of the world where starvation is a threat). I attached the article, just in case you would be interested in reading it. Maybe Soylent is the solution for not only addressing world hunger in a practical way, but also delaying the onset of age-related disorders.

    http://www.huffingtonpost.com/2013/11/13/soylent-documentary_n_4266853.html

    There is also a follow-up article:
    http://www.vice.com/read/rob-rhinehart-interview-soylent-never-eat-again

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  2. While it may be a source of extended lifespan, an extremely reduced caloric intake also can have effects on the functioning of the human body in general, which would change how we live. For instance, with reduced calorie intake, there is a theory that the body's focus is shifted from reproduction to somatic maintenance (Adler et al. 2013). After all, if an organism is barely getting enough nutrients to get by, then the focus is going to be shifted to allocating those resources to keep that organism alive instead of making more of itself in an environment where resources are already scarce. However, there was a difference found between males and females in this regard--while both had fertility compromised, females were rendered almost entirely infertile while males only experienced subtle changes under certain environmental conditions (Adler et al. 2013). This means that while dietary restriction may be a way for humans to extend their lifespan, it could also lead to a decreased capacity for reproduction in an era where people are already concerned about their fertility. Implementing a DR diet for humans would involve a total shift in lifestyle that most would not be willing to make.

    References:
    Adler MI, Cassidy EJ, Fricke C, Bonduriansky R. 2013 Jun. The lifespan-reproduction trade-off under dietary restriction is sex-specific and context-dependent. Experimental Gerontology. 48(6): 539-548.

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