Cellular ageing

We accept that life is finite and ageing inevitable. But we explore all options to battle the diseases that come with ageing. If we want to be able to postpone, or even prevent age related disease, we need to understand what changes in an ageing body. Ageing is, however, an incredibly complex phenomenon. Why can pine trees live thousands of years, while a mayfly lives minutes? Or within species, why do some people live to become 123, while most live till their 80s? Humans are built of trillions of cells of different types. In some complex way, the health state of all these cells is equal to the health state of a person as a whole.

To understand the age-related changes in cells on a molecular level, it makes sense to use a model organism, like the yeast. Baker’s yeast is a unicellular organism, meaning one cell is the whole organisms. Many genes that extend lifespan in yeast also do so in worms, flies, and mice. So yeast ageing measured in one cell is a model for ageing organisms much larger than yeast. What does the life of a yeast cells look like? A yeast cell produces a new cell approximately every two hours. A harmless scar is left behind on the mother, but changes inside the mother have begun to take place that are not yet fully understood and contribute to its ageing.

A mother cell that has produced 10 daughters has 10 scars. And we say her replicative age is 10. After the cell has produced between some 20 to 30 daughter cells, it dies. The daughter cells have youthful characteristics. This must mean that the daughter cell did not inherit whatever it is that killed her mother. Looking inside a cell, you’ll see a world of its own. Biologists have described it to a great extent.

This resembles a little factory. It is a ribosome that is making a protein. This resembles a power plant. It is a mitochondrion making energy. This resembles a library. It is the nucleus that keeps the chromosomes, the book of life. Molecular copy machines can copy the DNA. All parts of this molecular world inside the cell communicate and work together, for which there are means of communication and transport. This is, for example, a motor protein that carries a vesicle.

If everything in this small, one-celled world works well, and provided conditions are right, the cell will produce an extra copy of everything inside the cell so that when some two to three hours later, when a new cell is born, it is equipped with everything required.

So how is an old yeast cell different from a young yeast cell? When we compare them, we see that the molecular world in an old cell is indeed different. For making a daughter cell, it would be perfect if double the amount of everything inside the cell was made. But instead, the mother cell makes a bit too much of some parts, and too little of others. Also some parts wear down more easily than others. This is a problem if components have to work together to be functional. Dysfunctional and potentially harmful molecular machines appear. Brave mother tries her best to keep all these damaged molecular machines to herself, and to equip the daughter cell with a perfect set of molecular machines.

This now was the example of how ribosome function main impact ageing. But the big question for the coming years is to dissect cause and consequence. So just to name some, are mistakes on the DNA, the book of life, a first cause, or are they a consequence of malfunctioning molecular machines for copying that DNA? Could it be that these molecular copying machines are not doing their jobs well because the ribosomes, the little factories, produce them in a dysfunctional state? Finding these, and many other putatively causal relationships will be critical to understanding cellular ageing. We believe the strategy to work with a well controlled model system pays back when dealing with complex issues like ageing.