Discussing SKN-1 and the Extracellular Matrix in Aging

Here is a brief look at one small slice of research efforts focused on aging as it pertains to the extracellular matrix, the intricate structure of proteins that surrounds and supports cells. The arrangement of extracellular matrix proteins determines the mechanical properties of a given tissue, such as elasticity or ability to bear load:

The Blackwell lab focuses on research in healthy aging and lifespan by studying the model organism C. elegans, which is a type of worm. The lab specifically focuses on understanding oxidative stress responses and collagen development profiles in relation to lifespan. A simplified way of thinking about how collagen and extracellular matrix relate to lifespan is that as one grows older, the collagen and extracellular matrix slowly breakdown and are not as quickly repaired when injured. This is seen most prominently in cartilage-based injuries. Cartilage is made of collagen and extracellular matrix. A knee injury affecting the cartilage will heal much faster in young individuals than older individuals.

In C. elegans the SKN-1 gene plays a key role in promoting longevity through various pathway regulation including proteasome maintenance, stress resistance, immunity and lipid metabolism. One of the more surprising findings from these studies was the observation that SKN-1 was also involved in regulation of extracellular matrix genes and the resulting collagen expression profiles that change as the organism ages. SKN-1 dependent extracellular matrix remodeling is critical for lifespan extension in C. elegans. Several longevity interventions that delay aging are, in part, successful due to enhancing the function of extracellular structures.

C. elegans is the simplest multicellular animal with tissues that can conceivably be compared to humans. It was originally chosen in the 1970s as a model organism. Some of its advantages are that it reproduces in a few days and it self-fertilizes, which can make genetic manipulation much easier. It is a great organism for studying aging, because you can do so much to it genetically, and you can see the effects of aging in a short amount of time. With respect to translatability, I think there is a tendency to always question that. But worms and humans share the most fundamental processes, and the most basic wiring is there. So for testing an idea or delving into the unknown, C. elegans is a great organism to start with.

Humans have a much more complex profile of collagens, so it is hard to draw direct comparisons literally. However, I think the remodeling of the extracellular matrix and collagen is important in human aging. As an example, collagen decreases in the skin with age, as does the elasticity, and as elasticity decreases this further drives a decrease in collagen levels. The extracellular matrix is certainly an area that could use further studies on the effects of aging on the matrices to evaluate what changes occur over time.

Link: http://sage.buckinstitute.org/?p=951


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