Studying aging with synthetic biology

My labmate Bruno's newest paper, "A synthetic circuit for selectively arresting daughter cells to create aging populations" came out today in the journal Nucleic Acids Research (and it's open access!). Using a cleverly designed genetic circuit that activates cell growth arrest in newly divided cells only in the presence of a drug, Bruno was able to create a population of yeast made up of only old cells, called the "daughter arrester."

i-852a61e443e5216655d75a6c2a5cc493-gkq075f1-thumb-510x412-40885.jpegYou would think that yeast, being so single celled and bread-y, wouldn't be able to tell us much about human biology or anything as complex as aging, but many of the cellular processes that happen in our cells exist in yeast, and it's a lot easier to study yeast than it is to study humans (you certainly couldn't make a "daughter arrester" in humans). A lot about what we know about how cell growth is controlled (with huge implications for our understanding of cancer) comes from studies done in yeast, and more recently yeast has emerged as a useful model system for understanding mechanisms of cellular aging.

i-53e5f05c86936b101ad8755afdea7d76-saccharomyces.jpgSaccharomyces cerevisiae is known as budding yeast, meaning that when it multiplies it doesn't split in half like many other asexual organisms, but rather that a new cell "buds" off of the old one. The "mother" cell will keep budding off more "daughters", which will themselves become mothers when they get large enough. A mother cell can only bud off so many times, however, before it starts to slow down, age, and eventually die. The mechanisms controlling this aging process are not well understood. Why can't the cell divide indefinitely? Is the aging "programmed" in the DNA or is it something else, like oxidative stress from metabolism? Can it be reversed or slowed down? It's difficult to study only older cells in a mixed culture of yeast, with millions of cells swirling around and budding constantly. Synthetic biology devices like the daughter arrester can therefore be useful for basic science research of aging by quickly isolating a population of aged cells for further study and characterization. As an engineered device, the daughter arrester can also be incorporated as one component in a more complex synthetic system where control of cell growth and death are necessary.

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Dear Nick, I tried to add the techno song I made - based on evolutionary algorithms no less - as supplemental data but they wanted none of it. :-(

There's no law of nature constraining lifespan from being infinite, which is incredibly and absolutely fascinating. This to me, next to the study of the conscious brain, is on par to the study of atoms during the time of Rutherford, the structure of DNA during the 50s, the elaboration of the unit in the nervou system during the time of Golgi, and Cajal, etc.

I was going to make a video on aging, using shots of the replication fork and life of a cell with those of alive and dead animals - but that was a disaster. I watched it afterwards and it was like someone took a dagger to my heart. The physiological effects of death of someone close, just for one, is huge, imagine the full realization that for everything thats born, one dies (more or less, the spirit is the important thing).

Alright here's some wisdom, and I've actually thought about this a lot. Watch biovisions life of a cell, and realize those thousands of mitochondria, those kinesin proteins, the 22 pairs of socks of chromosomes in phone chords of chromatin dna, the clutter and hubbub of the cell city- is what it's like for practically all cells. I don't really think that's appreciated enough, and maybe experiments with this train of thought will lead to new discoveries, all because investigators are going to a deeper smaller level. Imagine one of these cells early on during development, than a newley created one 90 years later from those early dna socks, I wouldn't be surprised if those 'horseless carriage' mitochondria are slamming into microtubulues like drunk drivers, the contruction of the actin bridge highway throughout looks like it was setup by a 14 year old, etc. There has to be some general idea suggeting that the early cell cities representing the young organism compared to the later cell city leads to 'what the human perceives as aging - rough skin, skin spots, less muscle, whatever'.

I'm wondering if just the destruction of one of the later cell compartments can lead to disaster in that cell, and all sorts of problems from different causes lead to the death of the organism just from time and other accumulated alterations. We tend to forget that the early cell is 3.5 billion years of 'what's worked' - that it's not designed by Da Vinci - and it just doesn't collapse at the start. I'm sure in reality the 'clue' God has planted for us to find leads on to more interesting things he's veiled.. so it should be neat