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If you are thinking of starting to take Rapamycin for its general health benefits start by photographing your nails

Now this might seem an odd suggestion. However, if you are starting Rapamycin I think you should first photograph your nails. That is because Rapamycin affects the growth of many people's fingernails and you may wish to titrate your usage of Rapamycin by how you see the effects on your nails.

Rapamycin is known as an mTOR inhibitor. mTOR is a kinase in each cell that passes signals around relating to cell growth. If mTOR is activated then there is plenty of nutrients and so the cell can get on with building things. If mTOR is inactive it means nutrients are scarce and the cell needs to start recycling things to make them more efficient. Hence inhibiting mTOR (through the use of Rapamycin or fasting) can get the cell to start the process of autophagy

The particular aspect of autophagy that is very useful is mitophagy where the cell starts recycling mitochondria. The less efficient mitochondria have a lower MMP (Mitochondrial Membrane Potential) {normally} and the cell autophagy process knows to recycle the mitochondria with a lower membrane potential first.

This process is really good because the cell then replicates the more efficient mitochondria and things that were not working from a shortage of energy (normally indicated by levels of acetyl-CoA in the cytosol which reflects the average MMP). Cells with less energy don't properly produce the full range of mRNA and hence don't produce all the proteins they ideally would. This causes a range of illnesses.

So. Lets take a lot of Rapamycin?

Hold on. Rapamycin also has negative effects. These also come from inhibiting mTOR. There is actually a temporary shortage of energy caused by the recycling of mitochondria before the new ones are created, but we have to live with that. More importantly Rapamycin has some clear negative affects that arise from the same chemical process (inhibiting mTOR) that the positive effects arise from.

A well known effect of Rapamycin is the reduction in the immune response. This arises from it inhibiting the creation of new white blood cells. Hence people who have had a transplant often take Rapamycin to hold back the immune system. Rapamcyin, however, holds back all types of cells from dividing. This affects other stem cells.

This is where nail growth comes in. Nails grow by the process of stem cells dividing. This is the same throughout the body, but it is more obvious with nail growth as that is external and can actually be measured although just knowing how often you have to cut your nails is a useful piece of information.

Very often if you look at your nails you will see a thing called a Lunula where the nail starts growing from the finger (a half moon). This is part of the matrix of the nail where most of the growth occurs. Not everyone has these and their size can be bigger and smaller. However, because Rapamycin holds back nail growth often the lunulae (plural of lunula) will disappear on some or all of your fingers after a few months of Rapamcyin. This does not always occur, however, and there is a balance to be struck between encouraging autophagy and discouraging stem cell growth. Hence if you photograph your nails before you start on Rapamycin you will have a good idea of what has changed and whether you should adjust the dosing or frequency of dosing of Rapamycin.

I personally take Rapamycin, but not that frequently. In fact most of my fingers and particularly my thumbs do have lunulae on them, but sadly I don't have a photograph before I started. Hence I don't know what has changed. That is why I recommend anyone thinking about starting Rapamycin should start by photographing their fingernails.

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