SIRT1 Sits at the Center of a Web

In a complex, evolved system like our cells, everything connects to everything else. Evolution is adept at generating systems with a lot of reuse, feedback loops, and the same component performing multiple simultaneous jobs. It does make it very challenging for researchers to determine what is going on in our metabolism, however. Isolating a gene and the protein it produces because it is important to a cellular process you are interested in barely gets your foot into the door - then must follow years of tracing relationships to other genes, proteins, mechanisms, and so forth.

Over recent years it has become clear that the gene SIRT1 is important to the health and longevity benefits of calorie restriction. It has also become clear that SIRT1 is very well connected inside the cell, being involved in any number of aspects of our metabolism. So while, for example, one group has good evidence that SIRT1 works by promoting repair processes involving heat shock proteins, we also see that is important to the regulation of autophagy, another process well-linked with health and longevity benefits.

SIRT1: Regulation of longevity via autophagy

Recent studies have emphasized the importance of SIRT1, a mammalian homolog of Sir2 longevity factor, in the regulation of metabolism, cellular survival, and organismal lifespan. The signaling network interacting with SIRT1 continues to expand as does the number of functions known to be regulated by SIRT1.

Autophagy is also an emerging field in longevity studies. [Autophagy] is a housekeeping mechanism cleaning cells from aberrant and dysfunctional molecules and organelles. The extension of lifespan has been linked to the efficient maintenance of autophagic degradation, a process which declines during aging. Interestingly, recent observations have demonstrated that SIRT1 regulates the formation of autophagic vacuoles, either directly or indirectly through a downstream signaling network.

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The interactions of SIRT1 [can] also regulate both the autophagic degradation and lifespan extension emphasizing the key role of autophagy in the regulation of lifespan.

Interesting, altering SIRT1 on its own, such as through the use of calorie restriction mimetic drugs, doesn't appear to gain anywhere near the entire benefit of calorie restriction. So other mechanisms are at work in addition to those uncovered through exploring SIRT1's connections.

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