The search for immortality

Ageing has always been a subject of great interest and intrigue. In particular, how to prevent it is probably one of the key goals in life of scientists and millionaires, and desired by all at some point or other.

It’s a rather selfish objective when there are so many people suffering from other diseases that require our attention. Yet ageing is still a rather substantially funded research area as you can see:

NIHresearchspending

I made this chart using categorical spending figures from the NIH website. For the whole list, see here.

However, the thing about ageing is that growing old increases the risk of developing various diseases. So it kind of makes sense to understand it. But how does one go about studying ageing?

1. Look at rapidly ageing human models.

Progeria is a disease that resembles rapid ageing – skin gets wrinkled, muscles waste and hip dislocation can occur easily. This disease is highly linked to mutations in a gene encoding Lamin A, a protein found at the inner edges of cell nuclei  that helps maintain nuclear stability. The mutation produces a splice site, resulting in a truncated form of Lamin A that is unable perform its nuclear support function, giving rise to abnormally shaped nuclei. Interestingly, senescent cells (i.e. cells that have stopped dividing) also express this truncated form of Lamin A, indicating it tends to appear on ageing.

Hutchinson-Gilford_Progeria_Syndrome.png

Image from Wikipedia-Progeria. A young girl with progeria (left). A healthy cell nucleus (right, top) and a progeric cell nucleus (right, bottom).

2. Try to extend lifespan in model organisms

Worms, flies and yeast all have two things in common aside from being invertebrates, they’re easy to genetically manipulate and they do not live very long. This makes them ideal for reverse genetics where scientists screen thousands of genes, knocking each one down to see whether lifespan is extended. The African Killifish which lives for 3 months is now being used more and more for ageing research and Amber Dance wrote a great article on it recently.

This nice infographic shows the range of choice in model organisms (from the article “Live Fast Die Young” by Amber Dance):

ageing models.jpg

Strangely enough, there is little overlap between genes implicated in premature ageing diseases and genes that have extended lifespan in model organisms (such as mammalian target of rapamycin or mTOR and p53-related genes). However, it may be that the genes overlap in terms of downstream pathways and molecular mechanisms. So far it seems oxidative stress, protein homeostasis and TOR signalling may play larger roles.

In particular the mTOR inhibitor, rapamycin, has proven to actually extend lifespan in yeast, mice and now dogs. However it comes with some rather nasty side effects so it may not quite be the life-extending elixir we are looking for. And so the search continues…

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