Tuesday, January 17, 2017

Easing Aging by Yamanaka Factors?

Article Highlight Reel of the Week:

This week I'm focusing on the article: "In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming" which was published in Cell recently. 

Here is the background you need to know to understand this paper:

Stem cells are a type of cell that can develop into different types of cells. Put simply, a pluripotent stem cell has a lot of potential to be just about anything when it grows up. Like a child pondering what he or she can be, it has many paths it can take in development before it turns into its final adult career*. However, as it differentiates and goes down the path to maturity, its options of what it can be dwindles. Once it is a mature cell, it can't revert back to its pluripotent state (without some help from scientists).

The potency of a stem cell refers to how many possible types of cell your stem cell could become. If the maturing cell is unipotent, that means it must be at stage of differentiation where it can only become one cell type. If it is pluripotent, it can become just about any cell type in the body.

There are three sources of stem cells known. Those are: adult stem cells (which you have right now), embroyonic stem cells (which are derived from a 5 day old blastocyst), and induced pluripotent stem cells (iPSC) which are the subject of this paper.

Shinya Yamanaka won the Nobel Prize in medicine in 2012 for discovering four genes that when expressed can take a mature cell back to its pluripotent stem cell stage. The problem is these cells, though they appear to be brought back to a state of youth, can grow into cancer. So, the simple idea of applying Yamanaka factors haphazardly just doesn't work.

Here are the highlight discoveries:

Scientists from the Salk Insitute figured out that they could turn the Yamanka genes on and off before cells reached a totally pluripotent state (in which the cells could turn to cancer).

The way they did this was by designing mice with Yamanaka genes which could be activated or repressed when the mice ingest a substance in their water. They activated Yamanaka genes for two days and repressed them for five in cyclic fashion.

Mice who had progeria, which is a disease that causes one to age quickly, lived 30% longer than their average lifespan. Normal mice showed less aging characteristics. However, this beneficial effect did not last long after treatment stopped.
Image result for progeria
Child With Progeria

So, in brief, this study showed that cyclicly turning on Yamanka factors appears to slow aging in mice.

Why it's a Cool Paper:

The problem of pluripotent stem cells forming cancer cells has been a key issue of applying iPScs in human health care.

Even though we won't be doing gene editing on people to replicate this experiment, this study can be a springboard to study how epigenetics (a subfield of genetics which studies how genes get turned on and off at certain times for certain reasons) relates to aging. Who knows? Perhaps from this knowledge a sensible antiaging therapy could develop in the future. 

But no antiaging water just yet...

Additional Sources and Reading:
Image Source: The Cell Nucleus and Aging: Tantalizing Clues and Hopeful Promises. Scaffidi P, Gordon L, Misteli T. PLoS Biology Vol. 3/11/2005, e395 doi:10.1371/journal.pbio.0030395

*(ignore the fact that most people have many careers in their lifetime for metaphor sake)