Hi everyone! Apologies to those of you who follow me for the lack of postings over the past 2 weeks – things have been pretty hectic! However, as of now, I’m back on track and I’ll be bringing you 2 main posts this week to make up for the wait. This first one has been inspired by my reading Oscar Wilde’s ‘The Picture of Dorian Gray‘ – the story of a young man so consumed with his youth and beauty that he offers up his soul in order to retain his glory. I stumbled upon a research article into the damaging effects of ageing on the blood, which, given my reading material, struck a chord, so I thought I’d share what I read.
We all know that, as we get older, our bodies suffer – our bones become more brittle, we become weaker and, as I’ll discuss here, we become more susceptible to illnesses, including blood disorders. But why does all this happen? Well, for the most part, the cells from which we are made do not live very long. They are constantly dying and being replaced because of the countless toxins and physical pressures they have to cope with as they keep our bodies functioning properly. Imagine a weightlifter trying to hold his personal best above his head whilst someone continually punches him in the stomach and you’re probably on the right track! Replacements develop from special cells called stem cells. When first created, they have no specific function other than to make copies of themselves to maintain their numbers. However, stem cells have the potential to irreversibly take on the role of any other cell type when required. So, given this, why do stem cells don’t make us immortal? It is thought that their ability to function lessens over time, meaning that, eventually, fewer and fewer dead cells are replaced. The question is, in what way do they stop working?
Researchers at the University of California, San Francisco, have investigated this by looking specifically at stem cells made in the bone marrow – Haematopoietic Stem Cells (HSCs). These cells are responsible for replacing blood cells. When they don’t perform this role properly, as in aged individuals, numbers of healthy blood cells are reduced and unhealthy or dangerous cells and toxins become more prominent, resulting in blood disorders. This work aimed to understand why HSCs become less adept at producing healthy cells by studying their ability to carry out two essential cellular tasks: Autophagy and Apoptosis.
Autophagy involves sealing off, and breaking down, damaged or unnecessary cellular machinery. Normally, the resulting pieces can be used to build new machinery (like breaking down a Lego model to build a new one). During periods of starvation, however, they can be used as a source of nutrients and energy.
Apoptosis, meanwhile, essentially means ‘cell suicide’. Cells, including stem cells, that are severely damaged or unable to perform their given tasks can kill themselves.
The research group genetically engineered HSCs from mice so that they did not possess certain genes involved in these 2 processes – this is called a ‘gene knockout‘ technique. If a cell does not possess a certain gene then that gene cannot do its job. Scientists use this method to see exactly what roles individual genes play in a cell. The modified HSCs were exposed to both normal bloodstream-like conditions and those seen during periods of starvation. The group made the following observations (with the exception of the first one) by knocking out various genes and monitoring the effects they had on cell survival:
1. HSCs are far more capable of employing autophagy to react to starvation than other cells in the bone marrow. This is a well-known trait of stem cells.
2. Autophagy, as a process, exists to protect cells – if they can repair themselves then they don’t need to destroy themselves via apoptosis. As HSCs are excellent at launching autophagic responses, they can live and function longer than other blood cells before resorting to apoptosis.
3. HSCs possess a set of genes, which ensure that HSCs are always primed and ready to become autophagic quickly, to avoid starvation, damage and death.
4. Older HSCs are just as capable of launching an autophagic response as younger HSCs. In fact, it seems that the cells rely on the process to survive as they slowly lose the ability to uptake nutrients and produce energy.
This research proves to be something of a first step, rather than a full conclusion, in my opinion. We now know that autophagy is essential to stem cell survival and occurs properly, even in old age. However, that leaves us asking what happens – what breaks – in stem cells to cause them to slowly malfunction and die? Regardless, I hope you agree that this is a very interesting step closer to discovering why our blood system ages and deteriorates. I particularly like the idea that, as malfunctioning cells and harmful toxins build up and blood disorders become more likely, the failing HSCs remain obsessed with trying to keep themselves young, much like a certain Mr Gray…
This post was based on Warr, M. R. et al. (2013). FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature 494 (7437) 323-7.